WorldWideScience

Sample records for dwarfism

  1. Dwarfism

    Science.gov (United States)

    ... often includes stereotypes. Misconceptions can impact a person's self-esteem and limit opportunities for success in school or ... http://www.mayoclinic.org/diseases-conditions/dwarfism/basics/definition/CON-20032297 . Mayo Clinic Footer Legal Conditions and ...

  2. Dwarfism

    Science.gov (United States)

    ... might have: cleft palate hand and ear differences hip dysplasia club feet severe curvature of the spine early deterioration of joints and joint stiffness potential hip and knee dislocation Complications From Spondyloepiphyseal Dysplasia People with this type of dwarfism might have: ...

  3. Primordial dwarfism: an update.

    Science.gov (United States)

    Alkuraya, Fowzan S

    2015-02-01

    To review the recent advances in the clinical and molecular characterization of primordial dwarfism, an extreme growth deficiency disorder that has its onset during embryonic development and persists throughout life. The last decade has witnessed an unprecedented acceleration in the discovery of genes mutated in primordial dwarfism, from one gene to more than a dozen genes. These genetic discoveries have confirmed the notion that primordial dwarfism is caused by defects in basic cellular processes, most notably centriolar biology and DNA damage response. Fortunately, the increasing number of reported clinical primordial dwarfism subtypes has been accompanied by more accurate molecular classification. Qualitative defects of centrioles with resulting abnormal mitosis dynamics, reduced proliferation, and increased apoptosis represent the predominant molecular pathogenic mechanism in primordial dwarfism. Impaired DNA damage response is another important mechanism, which we now know is not mutually exclusive to abnormal centrioles. Molecular characterization of primordial dwarfism is helping families by enabling more reproductive choices and may pave the way for the future development of therapeutics.

  4. MR imaging of pituitary dwarfism

    Energy Technology Data Exchange (ETDEWEB)

    Kashimada, Akio; Machida, Kikuo; Honda, Norinari; Mamiya, Toshio; Takahashi, Taku; Kamano, Tsuyoshi; Muramatsu, Masayuki; Inoue, Yusuke (Saitama Medical School, Kawagoe (Japan). Medical Center)

    1993-02-01

    Pituitary MR imaging was performed in 32 patients with clinically diagnosed pituitary dwarfism and 12 normal controls. The patients were divided into two groups according to the severity of pituitary dwarfism based on endocrinological data. The two patients with severe dwarfism showed transection of the pituitary stalk, ectopic posterior lobe and atrophy of the anterior lobe on MR imaging, while the 27 patients with mild dwarfism showed no abnormal MR findings of the pituitary gland. The former group corresponds to typical pituitary dwarfism and the latter to partial GH deficiency, which was recently proposed as another type of pituitary dwarfism. In conclusion, pituitary MR imaging may differentiate partial GH deficiency from typical (stalk-transected) pituitary dwarfism. (author).

  5. Shedding light on canine pituitary dwarfism

    NARCIS (Netherlands)

    Voorbij, A.M.W.Y.

    2015-01-01

    Pituitary dwarfism, associated with growth hormone deficiency, is an autosomal, recessively inherited disorder in shepherd dogs. Due to the serious nature of pituitary dwarfism and lack of efficient treatment, it is preferable to prevent dwarfs from being born by applying a correct breeding policy.

  6. Shedding light on canine pituitary dwarfism

    NARCIS (Netherlands)

    Voorbij, A.M.W.Y.

    2015-01-01

    Pituitary dwarfism, associated with growth hormone deficiency, is an autosomal, recessively inherited disorder in shepherd dogs. Due to the serious nature of pituitary dwarfism and lack of efficient treatment, it is preferable to prevent dwarfs from being born by applying a correct breeding policy.

  7. Dwarfism and gigantism in historical picture postcards.

    Science.gov (United States)

    Enderle, A

    1998-05-01

    A collection of 893 historical picture postcards from 1900 to 1935, depicting dwarfs and giants, was analysed from medical and psychosocial viewpoints. In conditions such as 'bird headed dwarfism', achondroplasia, cretinism, so-called Aztecs or pinheads, Grebe chondrodysplasia, and acromegalic gigantism, the disorder could be diagnosed easily. In hypopituitary dwarfism, exact diagnosis was more difficult because of heterogeneity. The most common conditions depicted were pituitary dwarfism and achondroplasia. Most of those with gigantism had pituitary gigantism and acromegaly. Brothers and sisters or parents and their children provided evidence of mendelian inheritance of some of these disorders. The cards suggest that being put on show provided, at least in some cases, social benefits.

  8. Partial nephrectomy in a patient with dwarfism.

    Science.gov (United States)

    Farber, Nicholas J; Dubin, Justin; Parihar, Jaspreet; Han, Chris; Lasser, Michael S

    2016-08-01

    We describe the case of a 50-year-old male with achondroplastic dwarfism who presents with a renal mass in his left kidney concerning for renal cell carcinoma. The patient successfully underwent a robotic partial nephrectomy, which revealed a T1a renal cell carcinoma. The tumor was excised successfully without any intraoperative complications demonstrating that a robotic partial nephrectomy is technically both safe and effective in patients with achondroplastic dwarfism.

  9. Genetics Home Reference: microcephalic osteodysplastic primordial dwarfism type II

    Science.gov (United States)

    ... Twitter Home Health Conditions MOPDII microcephalic osteodysplastic primordial dwarfism type II Printable PDF Open All Close All ... the expand/collapse boxes. Description Microcephalic osteodysplastic primordial dwarfism type II ( MOPDII ) is a condition characterized by ...

  10. Dwarfism and gigantism in historical picture postcards.

    Science.gov (United States)

    Enderle, A

    1998-01-01

    A collection of 893 historical picture postcards from 1900 to 1935, depicting dwarfs and giants, was analysed from medical and psychosocial viewpoints. In conditions such as 'bird headed dwarfism', achondroplasia, cretinism, so-called Aztecs or pinheads, Grebe chondrodysplasia, and acromegalic gigantism, the disorder could be diagnosed easily. In hypopituitary dwarfism, exact diagnosis was more difficult because of heterogeneity. The most common conditions depicted were pituitary dwarfism and achondroplasia. Most of those with gigantism had pituitary gigantism and acromegaly. Brothers and sisters or parents and their children provided evidence of mendelian inheritance of some of these disorders. The cards suggest that being put on show provided, at least in some cases, social benefits. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:9764085

  11. Extreme insular dwarfism evolved in a mammoth.

    Science.gov (United States)

    Herridge, Victoria L; Lister, Adrian M

    2012-08-22

    The insular dwarfism seen in Pleistocene elephants has come to epitomize the island rule; yet our understanding of this phenomenon is hampered by poor taxonomy. For Mediterranean dwarf elephants, where the most extreme cases of insular dwarfism are observed, a key systematic question remains unresolved: are all taxa phyletic dwarfs of a single mainland species Palaeoloxodon antiquus (straight-tusked elephant), or are some referable to Mammuthus (mammoths)? Ancient DNA and geochronological evidence have been used to support a Mammuthus origin for the Cretan 'Palaeoloxodon' creticus, but these studies have been shown to be flawed. On the basis of existing collections and recent field discoveries, we present new, morphological evidence for the taxonomic status of 'P'. creticus, and show that it is indeed a mammoth, most probably derived from Early Pleistocene Mammuthus meridionalis or possibly Late Pliocene Mammuthus rumanus. We also show that Mammuthus creticus is smaller than other known insular dwarf mammoths, and is similar in size to the smallest dwarf Palaeoloxodon species from Sicily and Malta, making it the smallest mammoth species known to have existed. These findings indicate that extreme insular dwarfism has evolved to a similar degree independently in two elephant lineages.

  12. An unusual association of microcephalic osteodysplastic primordial dwarfism type I with cardiac and brain anomalies.

    Science.gov (United States)

    Bhutia, Euden; Verma, Arushi; Gupta, Amit Kumar; Maria, Arti

    2014-01-01

    Less than 100 cases of primordial dwarfism have been reported worldwide out of which Microcephalic osteodysplastic primordial dwarfism type I comprise about primordial dwarfism of antenatal onset due to Microcephalic osteodysplastic primordial dwarfism type I. Our case is also unique in being associated with hitertho unreported association of subpulmonic ventricular septal defect and a dorsal interhemispheric cyst in the brain.

  13. Laron's Dwarfism: Studies on the Nature of the Defect

    Science.gov (United States)

    Elders, M. Joycelyn; And Others

    1973-01-01

    Laron's syndrome, characterized by severe dwarfism, high circulating levels of immunoreactive growth hormone, and failure to generate somatomedin after administration of human growth hormone, was studied in a boy 7 1/2 years of age. (MC)

  14. Laron's Dwarfism: Studies on the Nature of the Defect

    Science.gov (United States)

    Elders, M. Joycelyn; And Others

    1973-01-01

    Laron's syndrome, characterized by severe dwarfism, high circulating levels of immunoreactive growth hormone, and failure to generate somatomedin after administration of human growth hormone, was studied in a boy 7 1/2 years of age. (MC)

  15. New type of lethal short-limbed dwarfism

    Energy Technology Data Exchange (ETDEWEB)

    Nairn, E.R.; Chapman, S.

    1989-05-01

    Details are presented of a most unusual osteo-chondrodysplasia which presents with lethal neonatal short-limbed dwarfism, defective ossification and nodular calcification with cartilage. The features resemble one case previously described in the literature.

  16. Microcephalic osteodysplastic primordial dwarfism type 1.

    Science.gov (United States)

    Ferrell, Steven; Johnson, Aaron; Pearson, Waylon

    2016-06-16

    Microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1) is an uncommon cause of microcephaly and intrauterine growth retardation in a newborn. Early identifying features include but are not limited to sloping forehead, micrognathia, sparse hair, including of eyebrows and short limbs. Immediate radiological findings may include partial or complete agenesis of the corpus callosum, interhemispheric cyst and shallow acetabula leading to dislocation. Genetic testing displaying a mutation in RNU4ATAC gene is necessary for definitive diagnosis. Early identification is important as MOPD1 is an autosomal recessive condition and could present in subsequent pregnancies. The purpose of this case is to both identify and describe some common physical findings related to MOPD1. We present a case of MOPD1 in a girl born to non-consanguineous parents that was distinct for subglottic stenosis and laryngeal cleft. 2016 BMJ Publishing Group Ltd.

  17. Current insights into the molecular genetic basis of dwarfism in livestock.

    Science.gov (United States)

    Boegheim, Iris J M; Leegwater, Peter A J; van Lith, Hein A; Back, Willem

    2017-06-01

    Impairment of bone growth at a young age leads to dwarfism in adulthood. Dwarfism can be categorised as either proportionate, an overall size reduction without changes in body proportions, or disproportionate, a size reduction in one or more limbs, with changes in body proportions. Many forms of dwarfism are inherited and result from structural disruptions or disrupted signalling pathways. Hormonal disruptions are evident in Brooksville miniature Brahman cattle and Z-linked dwarfism in chickens, caused by mutations in GH1 and GHR. Furthermore, mutations in IHH are the underlying cause of creeper achondroplasia in chickens. Belgian blue cattle display proportionate dwarfism caused by a mutation in RNF11, while American Angus cattle dwarfism is caused by a mutation in PRKG2. Mutations in EVC2 are associated with dwarfism in Japanese brown cattle and Tyrolean grey cattle. Fleckvieh dwarfism is caused by mutations in the GON4L gene. Mutations in COL10A1 and COL2A1 cause dwarfism in pigs and Holstein cattle, both associated with structural disruptions, while several mutations in ACAN are associated with bulldog-type dwarfism in Dexter cattle and dwarfism in American miniature horses. In other equine breeds, such as Shetland ponies and Friesian horses, dwarfism is caused by mutations in SHOX and B4GALT7. In Texel sheep, chondrodysplasia is associated with a deletion in SLC13A1. This review discusses genes known to be involved in these and other forms of dwarfism in livestock. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Mechanisms and pathways of growth failure in primordial dwarfism

    Science.gov (United States)

    Klingseisen, Anna; Jackson, Andrew P.

    2011-01-01

    The greatest difference between species is size; however, the developmental mechanisms determining organism growth remain poorly understood. Primordial dwarfism is a group of human single-gene disorders with extreme global growth failure (which includes Seckel syndrome, microcephalic osteodysplastic primordial dwarfism I [MOPD] types I and II, and Meier-Gorlin syndrome). Ten genes have now been identified for microcephalic primordial dwarfism, encoding proteins involved in fundamental cellular processes including genome replication (ORC1 [origin recognition complex 1], ORC4, ORC6, CDT1, and CDC6), DNA damage response (ATR [ataxia-telangiectasia and Rad3-related]), mRNA splicing (U4atac), and centrosome function (CEP152, PCNT, and CPAP). Here, we review the cellular and developmental mechanisms underlying the pathogenesis of these conditions and address whether further study of these genes could provide novel insight into the physiological regulation of organism growth. PMID:21979914

  19. Mechanisms and pathways of growth failure in primordial dwarfism.

    Science.gov (United States)

    Klingseisen, Anna; Jackson, Andrew P

    2011-10-01

    The greatest difference between species is size; however, the developmental mechanisms determining organism growth remain poorly understood. Primordial dwarfism is a group of human single-gene disorders with extreme global growth failure (which includes Seckel syndrome, microcephalic osteodysplastic primordial dwarfism I [MOPD] types I and II, and Meier-Gorlin syndrome). Ten genes have now been identified for microcephalic primordial dwarfism, encoding proteins involved in fundamental cellular processes including genome replication (ORC1 [origin recognition complex 1], ORC4, ORC6, CDT1, and CDC6), DNA damage response (ATR [ataxia-telangiectasia and Rad3-related]), mRNA splicing (U4atac), and centrosome function (CEP152, PCNT, and CPAP). Here, we review the cellular and developmental mechanisms underlying the pathogenesis of these conditions and address whether further study of these genes could provide novel insight into the physiological regulation of organism growth.

  20. Thanatophoric dwarfism. Two case reports and survey of the literature.

    Science.gov (United States)

    Nissenbaum, M; Chung, S M; Rosenberg, H K; Buck, B E

    1977-08-01

    Thanatophoric dwarfism is a severe form of short-limbed dwarfism in which cardiorespiratory failure uniformly results in death in the neonatal period. Its radiographic features include markedly flattened vertebral bodies with a typical U-shaped deformity, a flat squat pelvis, and short, bowed extremities with flaring and irregularity of the metaphyses. These characteristic features distinguish this entity from the two other most commonly confused congenital short-limbed forms of dwarism--achondroplasia and achondrogenesis. The distinctions are discussed in the text.

  1. Ectopic Neurohypophysis in Patient with Pituitary Dwarfism: A Case Report

    Directory of Open Access Journals (Sweden)

    İlhan Kılınç

    2008-09-01

    Full Text Available Ectopic neurohypophysis is an anomaly of the Pituitary gland whichmay be associated with short stature due to Growth hormone deficiency.MRI is the modality of choice in diagnosing this condition. We present acase of pituitary dwarfism and ectopic neurohypophysis with clinical andradiological findings. 21 year-old male admitted with short stature. Allhormones, except prolactin, of anterior hypophysis were low. Bright spotwas ectopically located at level of median eminence on enhanced MRI ofhypophysis and stalk of hypophysis was not observed. Ectopicneurohypophysis may be present with pituitary dwarfism. Cranial MRI maybe useful to investigate related pathologies in such cases.

  2. Renal tubular leakage complicating microcephalic osteodysplastic primordial dwarfism.

    Science.gov (United States)

    Eason, J; Hall, C M; Trounce, J Q

    1995-01-01

    We describe a male infant with phenotypic and radiological features of microcephalic osteodysplastic primordial dwarfism type I/III. He showed severe osteoporosis and biochemical derangement owing to renal tubular leakage, which has not previously been reported in this condition. He died aged 5 months. Images PMID:7783178

  3. Mutations in the pericentrin (PCNT) gene cause primordial dwarfism.

    NARCIS (Netherlands)

    Rauch, A.; Thiel, C.T.; Schindler, D.; Wick, U.; Crow, Y.J.; Ekici, A.B.; Essen, A.J. van; Goecke, T.O.; Al-Gazali, L.; Chrzanowska, K.H.; Zweier, C.; Brunner, H.G.; Becker, K.; Curry, C.J.; Dallapiccola, B.; Devriendt, K.; Dorfler, A.; Kinning, E.; Megarbane, A.; Meinecke, P.; Semple, R.K.; Spranger, S.; Toutain, A.; Trembath, R.C.; Voss, E.; Wilson, L.; Hennekam, R.C.M.; Zegher, F. de; Dorr, H.G.; Reis, A.

    2008-01-01

    Fundamental processes influencing human growth can be revealed by studying extreme short stature. Using genetic linkage analysis, we find that biallelic loss-of-function mutations in the centrosomal pericentrin (PCNT) gene on chromosome 21q22.3 cause microcephalic osteodysplastic primordial dwarfism

  4. Case report: Anesthesia management for emergency cesarean section in a patient with dwarfism.

    Science.gov (United States)

    Li, Xiaoxi; Duan, Hongjun; Zuo, Mingzhang

    2015-04-28

    Dwarfism is characterized by short stature. Pregnancy in women with dwarfism is uncommon and cesarean section is generally indicated for delivery. Patients with dwarfism are high-risk population for both general and regional anesthesia, let alone in an emergency surgery. In this case report we present a 27-year-old Chinese puerpera with dwarfism who underwent emergency cesarean section under combined spinal and epidural anesthesia. It is an original case report, which provides instructive significance for anesthesia management especially combined spinal and epidural anesthesia in this rare condition. There was only one former article that reported a puerpera who underwent combined spinal and epidural anesthesia for a selective cesarean section.

  5. Microcephalic Osteodysplastic Primordial Dwarfism, Type II: a Clinical Review.

    Science.gov (United States)

    Bober, Michael B; Jackson, Andrew P

    2017-04-01

    This review will provide an overview of the microcephalic primordial dwarfism (MPD) class of disorders and provide the reader comprehensive clinical review with suggested care guidelines for patients with microcephalic osteodysplastic primordial dwarfism, type II (MOPDII). Over the last 15 years, significant strides have been made in the diagnosis, natural history, and management of MOPDII. MOPDII is the most common and well described form of MPD. The classic features of the MPD group are severe pre- and postnatal growth retardation, with marked microcephaly. In addition to these features, individuals with MOPDII have characteristic facies, skeletal dysplasia, abnormal dentition, and an increased risk for cerebrovascular disease and insulin resistance. Biallelic loss-of-function mutations in the pericentrin gene cause MOPDII, which is inherited in an autosomal recessive manner.

  6. Mutations in XRCC4 cause primordial dwarfism without causing immunodeficiency.

    Science.gov (United States)

    Saito, Shinta; Kurosawa, Aya; Adachi, Noritaka

    2016-08-01

    In successive reports from 2014 to 2015, X-ray repair cross-complementing protein 4 (XRCC4) has been identified as a novel causative gene of primordial dwarfism. XRCC4 is indispensable for non-homologous end joining (NHEJ), the major pathway for repairing DNA double-strand breaks. As NHEJ is essential for V(D)J recombination during lymphocyte development, it is generally believed that abnormalities in XRCC4 cause severe combined immunodeficiency. Contrary to expectations, however, no overt immunodeficiency has been observed in patients with primordial dwarfism harboring XRCC4 mutations. Here, we describe the various XRCC4 mutations that lead to disease and discuss their impact on NHEJ and V(D)J recombination.

  7. Neonatal lethal dwarfism with distinct skeletal malformations - a separate entity?

    Energy Technology Data Exchange (ETDEWEB)

    Rosendahl, K.; Maurseth, K.; Olsen, Oe.E. [Dept. of Paediatric Radiology, Haukeland University Hospital, Bergen (Norway); Halvorsen, O.J. [Dept. of Pathology, Haukeland University Hospital, Bergen (Norway); Gjelland, K. [Dept. of Gynaecology, Haukeland University Hospital, Bergen (Norway); Engebretsen, L. [Dept. of Genetics, Haukeland University Hospital, Bergen (Norway)

    2001-09-01

    We describe a case of neonatal lethal dwarfism characterised by short trunk, short, stick-like tubular bones, deficient ossification of the axial skeleton and broad, sclerotic horizontal ribs. Two similar cases have previously been reported as examples of the Neu-Laxova syndrome. However, the radiological findings of the Neu-Laxova syndrome, as reported in 16 out of 40 documented cases, show a heterogeneous pattern of minor features, which differ distinctively from those found in the previous two cases and by us. A literature research did not reveal similar cases, and we therefore suggest that our case, together with the two previous cases, may represent a new distinctive form of neonatal lethal dwarfism. (orig.)

  8. RTTN Mutations Cause Primary Microcephaly and Primordial Dwarfism in Humans.

    Science.gov (United States)

    Shamseldin, Hanan; Alazami, Anas M; Manning, Melanie; Hashem, Amal; Caluseiu, Oana; Tabarki, Brahim; Esplin, Edward; Schelley, Susan; Innes, A Micheil; Parboosingh, Jillian S; Lamont, Ryan; Majewski, Jacek; Bernier, Francois P; Alkuraya, Fowzan S

    2015-12-03

    Primary microcephaly is a developmental brain anomaly that results from defective proliferation of neuroprogenitors in the germinal periventricular zone. More than a dozen genes are known to be mutated in autosomal-recessive primary microcephaly in isolation or in association with a more generalized growth deficiency (microcephalic primordial dwarfism), but the genetic heterogeneity is probably more extensive. In a research protocol involving autozygome mapping and exome sequencing, we recruited a multiplex consanguineous family who is affected by severe microcephalic primordial dwarfism and tested negative on clinical exome sequencing. Two candidate autozygous intervals were identified, and the second round of exome sequencing revealed a single intronic variant therein (c.2885+8A>G [p.Ser963(∗)] in RTTN exon 23). RT-PCR confirmed that this change creates a cryptic splice donor and thus causes retention of the intervening 7 bp of the intron and leads to premature truncation. On the basis of this finding, we reanalyzed the exome file of a second consanguineous family affected by a similar phenotype and identified another homozygous change in RTTN as the likely causal mutation. Combined linkage analysis of the two families confirmed that RTTN maps to the only significant linkage peak. Finally, through international collaboration, a Canadian multiplex family affected by microcephalic primordial dwarfism and biallelic mutation of RTTN was identified. Our results expand the phenotype of RTTN-related disorders, hitherto limited to polymicrogyria, to include microcephalic primordial dwarfism with a complex brain phenotype involving simplified gyration. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  9. Epidural anaesthesia for caesarean section in pituitary dwarfism.

    Science.gov (United States)

    Li, Hongbo; Li, Ruihua; Lang, Bao

    2017-04-01

    We describe the anaesthetic management for caesarean section in a 32-year-old patient with pituitary dwarfism. In addition to supportive treatment, we offered a postoperative epidural analgesia pump. The patient recovered well without any complications. Copyright © 2016 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

  10. Pituitary dwarfism in Saarloos and Czechoslovakian wolfdogs is associated with a mutation in LHX3

    NARCIS (Netherlands)

    Voorbij, AMWY; Leegwater, Peter; Kooistra, Hans

    2014-01-01

    Background Pituitary dwarfism in German Shepherd Dogs is associated with autosomal recessive inheritance and a mutation in LHX3, resulting in combined pituitary hormone deficiency. Congenital dwarfism also is encountered in breeds related to German Shepherd Dogs, such as Saarloos and Czechoslovakian

  11. Pituitary dwarfism in Saarloos and Czechoslovakian wolfdogs is associated with a mutation in LHX3

    NARCIS (Netherlands)

    Voorbij, AMWY; Leegwater, Peter; Kooistra, Hans

    Background Pituitary dwarfism in German Shepherd Dogs is associated with autosomal recessive inheritance and a mutation in LHX3, resulting in combined pituitary hormone deficiency. Congenital dwarfism also is encountered in breeds related to German Shepherd Dogs, such as Saarloos and Czechoslovakian

  12. Hereditary dwarfism in yellow lupin (Lupinus luteus L

    Directory of Open Access Journals (Sweden)

    Tadeusz Kazimierski

    2015-01-01

    Full Text Available A dwarf plant was found in the F4 generation of a hybrid between two yellow lupin subspecies. Genetic analysis demonstrated that the dwarf grwoth is conditioned by one recessive factor which was named nanus. This factor acts pleiotroipically since it reduces the height, changes the morphological structure and some anatomical traits and reduces fertility in the dwarf plants. It is believed that in the chromosome with translocation a gene block arose in the F4, plant. These genes acting as a compact system cause dwarfism, changes in the anatomical structure and reduce fertility.

  13. Anesthetic management for Cesarean delivery in parturients with a diagnosis of dwarfism.

    Science.gov (United States)

    Lange, Elizabeth M S; Toledo, Paloma; Stariha, Jillian; Nixon, Heather C

    2016-08-01

    The literature on the anesthetic management of parturients with dwarfism is sparse and limited to isolated case reports. Pregnancy complications associated with dwarfism include an increased risk of respiratory compromise, an increased risk of Cesarean delivery, and an unpredictable degree of anesthesia with neuraxial techniques. Therefore, we conducted this retrospective review to evaluate the anesthetic management of parturients with a diagnosis of dwarfism. We used a query of billing data to identify short statured women who underwent a Cesarean delivery during May 1, 2008 to May 1, 2013. We then hand searched the electronic medical record for qualifying patients with heights dwarfism. The extracted data included patient demographics and obstetric and anesthetic information. We identified 13 women with dwarfism who had 15 Cesarean deliveries in total. Twelve of the women had disproportionate dwarfism, and ten of the 15 Cesarean deliveries were due to cephalopelvic disproportion. Neuraxial anesthesia was attempted in 93% of deliveries. The dose chosen for initiation of neuraxial anesthesia was lower than the typical doses used in parturients of normal stature. Neuraxial anesthetic complications included difficult neuraxial placement (64%), high spinal (7%), inadequate surgical level (13%), and unrecognized intrathecal catheter (7%). The data collected suggest that females with a diagnosis of dwarfism may have difficult neuraxial placement and potentially require lower dosages of local anesthetic for both spinal and epidural anesthesia to achieve adequate surgical blockade.

  14. Phenotypic diagnosis of dwarfism in six Friesian horses.

    Science.gov (United States)

    Back, W; van der Lugt, J J; Nikkels, P G J; van den Belt, A J M; van der Kolk, J H; Stout, T A E

    2008-05-01

    An extreme form of abnormal development, dwarfism, is common in man and some animals, but has not been officially reported in horses. Within the Friesian horse breed, congenital dwarfism has been recognised for many years, but no detailed report exists on its phenotype. The most salient feature of the dwarf syndrome is the physeal growth retardation in both limbs and ribs. Affected animals have approximately 25% shorter fore- and hindlimbs and approximately 50% reduced bodyweight. Postnatal growth is still possible in these animals, albeit at a slower rate: the head and back grow faster than the limbs and ribs leading to the characteristic disproportional growth disturbance. Thus, adult dwarfs exhibit a normal, but a relatively larger head conformation, a broader chest with narrowing at the costochondral junction, a disproportionally long back, abnormally short limbs, hyperextension of the fetlocks and narrow long-toed hooves. Furthermore, a dysplastic metaphysis of the distal metacarpus and metatarsus is radiographically evident. Microscopic analysis of the growth plates at the costochondral junction shows an irregular transition from cartilage to bone, and thickening and disturbed formation of chondrocyte columns, which is similar to findings in osteochondrodysplasia.

  15. "Ocular moyamoya" syndrome in a patient with features of microcephalic osteodysplastic primordial dwarfism type II.

    Science.gov (United States)

    Bang, Genie M; Kirmani, Salman; Patton, Alice; Pulido, Jose S; Brodsky, Michael C

    2013-02-01

    Primordial dwarfism refers to severely impaired growth beginning early in fetal life. There are many genetic causes of primordial dwarfism, including disorders classified as microcephalic osteodysplastic primordial dwarfism. Microcephalic osteodysplastic primordial dwarfism type II is an autosomal-recessive disease characterized by small stature, bone and dental anomalies, and characteristic facies. Affected patients have a high risk of stroke secondary to progressive cerebral vascular anomalies, which often are classified as moyamoya disease. We present the case of a boy with features suggestive of MOPD II with unilateral moyamoya cerebrovascular changes and correlative moyamoya collaterals involving the iris of the ipsilateral eye. Copyright © 2013 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

  16. Pregnancy in a woman with proportionate (primordial) dwarfism: a case report and literature review

    Science.gov (United States)

    Vance, C E; Desmond, M; Robinson, A; Johns, J; Zacharin, M; Savarirayan, R; König, K; Warrillow, S; Walker, S P

    2012-01-01

    Primordial dwarfism is a rare form of severe proportionate dwarfism which poses significant challenges in pregnancy. A 27-year-old with primordial dwarfism (height 97 cm, weight 22 kg) and coexisting morbidities of familial hypercholesterolaemia and hypertension presented to our unit. Early pregnancy was complicated by difficult blood pressure control, sinus tachycardia, biochemical hyperthyroidism and insulin-requiring gestational diabetes. Delivery was indicated at 24 weeks with uncontrollable hypertension, progressive renal impairment and intrauterine growth restriction. A caesarean section was performed under general anaesthesia, resulting in the delivery of a 486 g male infant. This case highlights the difficulties of managing pregnancy in a woman with primordial dwarfism. Her limited capacity to respond to the physiological demands of pregnancy created a life-threatening situation, culminating in profound preterm birth. PMID:27582869

  17. Expanding the phenotypic and mutational spectrum in microcephalic osteodysplastic primordial dwarfism type I.

    Science.gov (United States)

    Abdel-Salam, Ghada M H; Abdel-Hamid, Mohamed S; Issa, Mahmoud; Magdy, Ahmed; El-Kotoury, Ahmed; Amr, Khalda

    2012-06-01

    Mutations in the RNU4ATAC gene cause microcephalic osteodysplastic primordial dwarfism type I. It encodes U4atac, a small nuclear RNA that is a component of the minor spliceosome. Six distinct mutations in 30 patients diagnosed as microcephalic osteodysplastic primordial dwarfism type I have been described. We report on three additional patients from two unrelated families presenting with a milder phenotype of microcephalic osteodysplastic primordial dwarfism type I and metopic synostosis. Patient 1 had two novel heterozygous mutations in the 3' prime stem-loop, g.66G > C and g.124G > A while Patients 2 and 3 had a homozygous mutation g.55G > A in the 5' prime stem-loop. Although they manifested the known spectrum of clinical features of microcephalic osteodysplastic primordial dwarfism type I, they lacked evidence of severe developmental delay and neurological symptoms. These findings expand the mutational and phenotypic spectrum of this syndrome. Copyright © 2012 Wiley Periodicals, Inc.

  18. Cultural stereotypes and personal beliefs about individuals with dwarfism.

    Science.gov (United States)

    Heider, Jeremy D; Scherer, Cory R; Edlund, John E

    2013-01-01

    Three studies assessed the content of cultural stereotypes and personal beliefs regarding individuals with dwarfism among "average height" (i.e., non-dwarf) individuals. In Studies 1 and 2, undergraduates from three separate institutions selected adjectives to reflect traits constituting both the cultural stereotype about dwarves and their own personal beliefs about dwarves (cf. Devine & Elliot, 1995). The most commonly endorsed traits for the cultural stereotype tended to be negative (e.g., weird, incapable, childlike); the most commonly endorsed traits for personal beliefs were largely positive (e.g., capable, intelligent, kind). In Study 3, undergraduates from two separate institutions used an open-ended method to indicate their personal beliefs about dwarves (cf. Eagly, Mladinic, & Otto, 1994). Responses contained a mixture of positive and negative characteristics, suggesting a greater willingness to admit to negative personal beliefs using the open-ended method.

  19. Primordial dwarfism: overview of clinical and genetic aspects.

    Science.gov (United States)

    Khetarpal, Preeti; Das, Satrupa; Panigrahi, Inusha; Munshi, Anjana

    2016-02-01

    Primordial dwarfism is a group of genetic disorders which include Seckel Syndrome, Silver-Russell Syndrome, Microcephalic Osteodysplastic Primordial Dwarfism types I/III, II and Meier-Gorlin Syndrome. This genetic disorder group is characterized by intra-uterine growth retardation and post-natal growth abnormalities which occur as a result of disorganized molecular and genomic changes in embryonic stage and, thus, it represents a unique area to study growth and developmental abnormalities. Lot of research has been carried out on different aspects; however, a consolidated review that discusses an overall spectrum of this disorder is not accessible. Recent research in this area points toward important molecular and cellular mechanisms in human body that regulate the complexity of growth process. Studies have emerged that have clearly associated with a number of abnormal chromosomal, genetic and epigenetic alterations that can predispose an embryo to develop PD-associated developmental defects. Finding and associating such fundamental changes to its subtypes will help in re-examination of alleged functions at both cellular and developmental levels and thus reveal the intrinsic mechanism that leads to a balanced growth. Although such findings have unraveled a subtle understanding of growth process, we further require active research in terms of identification of reliable biomarkers for different subtypes as an immediate requirement for clinical utilization. It is hoped that further study will advance the understanding of basic mechanisms regulating growth relevant to human health. Therefore, this review has been written with an aim to present an overview of chromosomal, molecular and epigenetic modifications reported to be associated with different subtypes of this heterogenous disorder. Further, latest findings with respect to clinical and molecular genetics research have been summarized to aid the medical fraternity in their clinical utility, for diagnosing disorders

  20. Successful treatment of dwarfism secondary to long-term steroid therapy in steroid-dependent nephrotic syndrome.

    Science.gov (United States)

    Sun, Linlin; Chen, Dongping; Zhao, Xuezhi; Xu, Chenggang; Mei, Changlin

    2010-01-01

    Prolonged steroid therapy is generally used for steroid-dependent nephrotic syndrome in pediatric patients. However, dwarfism secondary to a long-term regimen and its successful reverse is rarely reported. The underlying mechanism of dwarfism is still poorly understood, as both long-term steroid use and nephrotic syndrome may interact or independently interfere with the process of growth. Here, we present a 17-year-old patient with dwarfism and steroid-dependent nephrotic syndrome and the successful treatment by recombinant human growth factor and cyclosporine A with withdrawal of steroid. We also briefly review the current understanding and the management of dwarfism in pediatric patients with nephrotic syndrome.

  1. Genomic analysis of primordial dwarfism reveals novel disease genes.

    Science.gov (United States)

    Shaheen, Ranad; Faqeih, Eissa; Ansari, Shinu; Abdel-Salam, Ghada; Al-Hassnan, Zuhair N; Al-Shidi, Tarfa; Alomar, Rana; Sogaty, Sameera; Alkuraya, Fowzan S

    2014-02-01

    Primordial dwarfism (PD) is a disease in which severely impaired fetal growth persists throughout postnatal development and results in stunted adult size. The condition is highly heterogeneous clinically, but the use of certain phenotypic aspects such as head circumference and facial appearance has proven helpful in defining clinical subgroups. In this study, we present the results of clinical and genomic characterization of 16 new patients in whom a broad definition of PD was used (e.g., 3M syndrome was included). We report a novel PD syndrome with distinct facies in two unrelated patients, each with a different homozygous truncating mutation in CRIPT. Our analysis also reveals, in addition to mutations in known PD disease genes, the first instance of biallelic truncating BRCA2 mutation causing PD with normal bone marrow analysis. In addition, we have identified a novel locus for Seckel syndrome based on a consanguineous multiplex family and identified a homozygous truncating mutation in DNA2 as the likely cause. An additional novel PD disease candidate gene XRCC4 was identified by autozygome/exome analysis, and the knockout mouse phenotype is highly compatible with PD. Thus, we add a number of novel genes to the growing list of PD-linked genes, including one which we show to be linked to a novel PD syndrome with a distinct facial appearance. PD is extremely heterogeneous genetically and clinically, and genomic tools are often required to reach a molecular diagnosis.

  2. Becker and limb-girdle muscular dystrophy associated with pituitary dwarfism.

    Science.gov (United States)

    Marconi, G; Taiuti, R; Sbrilli, C; Pizzi, A

    1987-08-01

    In 1981 a report appeared of a patient with Duchenne muscular dystrophy associated with dwarfism caused by growth hormone deficiency, in whom the muscular disease was unusually benign. The authors suggested that the benign course might be related to the growth hormone deficiency and dwarfism. Other authors later supported this idea, having observed that in dystrophic mice and hamsters with congenital and experimentally induced pituitary dwarfism, respectively, pathological expressions of the dystrophy were markedly reduced. In this paper one case of Becker and one of limb-girdle dystrophy, each associated with short stature and growth hormone deficiency are described. In these cases the disease did not have a particularly benign course. It is concluded that caution is necessary, at least in certain cases, before an association between reduced muscular growth and the dystrophic process can be assumed.

  3. Survivorship and complications of total hip arthroplasty in patients with dwarfism.

    Science.gov (United States)

    Modi, Ronuk M; Kheir, Michael M; Tan, Timothy L; Penny, Gregory S; Chen, Chi-Lung; Shao, Hongyi; Chen, Antonia F

    2017-09-19

    Total hip arthroplasty (THA) is a common procedure used to treat bony hip deformities and skeletal dysplasia in dwarfism. These surgeries are often more difficult than conventional THA as they may involve malformed joints and poor bone quality, and may require smaller prostheses. This study aims to investigate whether implant survivorship and revision rates vary among patients with and without dwarfism undergoing THA. A retrospective case-control study was performed for 102 THAs completed between 1997 and 2014 in patients under the height threshold of 147.32 cm. This cohort was matched 1:1.5 with patients of normal height with respect to age, gender, year of surgery, and Charlson comorbidities. All cases had a minimum follow-up of 1 year. A chart review was performed to identify patient and surgical characteristics, including outcomes. Radiographs were assessed for deformity, loosening, and periprosthetic fractures among other factors. The 2-, 5-, and 10-year survivorship of THA in patients with dwarfism was 92.9%, 92.9%, and 80.7%, respectively; and 94.4%, 86.4%, and 86.4% for controls, respectively (p = 0.95). The dwarfism cohort demonstrated an OR of 3.81 and 3.02 for revision for periprosthetic fractures (p = 0.11) and mechanical wear (p = 0.21), respectively. THA in patients with dwarfism achieves comparable results to a non-dwarfism population with regards to implant survivorship; however, there is a trend toward increased periprosthetic fractures and wear-related failures. Surgeons should be aware of this potentially higher risk in this population and take morphological differences into account during surgical planning and technique.

  4. Dental Abnormalities in Pituitary Dwarfism: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Franco Ferrante

    2017-01-01

    Full Text Available Hypopituitarism is a disorder caused by a reduced level of trophic hormones that may be consequent on different destructive processes. The clinical manifestations depend on the type of hormone involved. A deficiency of growth hormone (GH in children causes the lack of growth known as pituitary dwarfism. The case is reported of a patient with pituitary dwarfism, multiple dental anomalies, functional prosthetic problems, and a revision of the literature. She was subjected to prosthetic rehabilitation without surgical intervention, using zirconium substructures, thus eliminating the potential complications that may require trauma surgery. The therapeutic approach adopted led to excellent results and restored an aesthetic smile.

  5. Chemotherapy dosing in achondroplastic dwarfism: a case report and review of literature.

    Science.gov (United States)

    Elsoueidi, R; Gresham, C; Michael, L; Chaney, D; Mourad, H

    2016-12-01

    CASE DESCRIPTION: A 74-year-old female with achondroplastic dwarfism was diagnosed with ER-, BR- and HER2- breast cancer. No guideline currently exists to direct chemotherapy dosing in this population. She received neoadjuvant chemotherapy based on body surface area utilizing actual height and weight with dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with the use of granulocyte colony-stimulating factor. Satisfactory clinical response and remission were achieved, and treatment proceeded without any significant toxicity or delays. In the absence of guideline recommendations, dosing chemotherapy based on actual height and weight in patients with achondroplastic dwarfism may be safe and appropriate. © 2016 John Wiley & Sons Ltd.

  6. Microcephalic osteodysplastic primordial dwarfism, with the fascinating history of "Mademoiselle Crachami".

    Science.gov (United States)

    Bozkaya, O Giray

    2013-01-01

    This review critically examines the findings which characterize the dysmorphic, radiologic and behavioral phenotype of Microcephalic Osteodysplastic Primordial Dwarfism (MOPD) and has an historical perspective on it. MOPD is a group of primordial dwarfism syndromes with prenatal onset growth retardation, a typical craniofacial appearance and behavioral phenotype. In 1959, Mann and Russell have described the first case in a detailed report, and named "microcephalic midget of extreme type". In their report; based on historical records and a small painting, they pointed "Mademoiselle Crachami" as the oldest known case.

  7. Mutations in the NHEJ component XRCC4 cause primordial dwarfism.

    Science.gov (United States)

    Murray, Jennie E; van der Burg, Mirjam; IJspeert, Hanna; Carroll, Paula; Wu, Qian; Ochi, Takashi; Leitch, Andrea; Miller, Edward S; Kysela, Boris; Jawad, Alireza; Bottani, Armand; Brancati, Francesco; Cappa, Marco; Cormier-Daire, Valerie; Deshpande, Charu; Faqeih, Eissa A; Graham, Gail E; Ranza, Emmanuelle; Blundell, Tom L; Jackson, Andrew P; Stewart, Grant S; Bicknell, Louise S

    2015-03-05

    Non-homologous end joining (NHEJ) is a key cellular process ensuring genome integrity. Mutations in several components of the NHEJ pathway have been identified, often associated with severe combined immunodeficiency (SCID), consistent with the requirement for NHEJ during V(D)J recombination to ensure diversity of the adaptive immune system. In contrast, we have recently found that biallelic mutations in LIG4 are a common cause of microcephalic primordial dwarfism (MPD), a phenotype characterized by prenatal-onset extreme global growth failure. Here we provide definitive molecular genetic evidence supported by biochemical, cellular, and immunological data for mutations in XRCC4, encoding the obligate binding partner of LIG4, causing MPD. We report the identification of biallelic mutations in XRCC4 in five families. Biochemical and cellular studies demonstrate that these alterations substantially decrease XRCC4 protein levels leading to reduced cellular ligase IV activity. Consequently, NHEJ-dependent repair of ionizing-radiation-induced DNA double-strand breaks is compromised in XRCC4 cells. Similarly, immunoglobulin junctional diversification is impaired in cells. However, immunoglobulin levels are normal, and individuals lack overt signs of immunodeficiency. Additionally, in contrast to individuals with LIG4 mutations, pancytopenia leading to bone marrow failure has not been observed. Hence, alterations that alter different NHEJ proteins give rise to a phenotypic spectrum, from SCID to extreme growth failure, with deficiencies in certain key components of this repair pathway predominantly exhibiting growth deficits, reflecting differential developmental requirements for NHEJ proteins to support growth and immune maturation. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  8. Hip pathology in Majewski osteodysplastic primordial dwarfism type II.

    Science.gov (United States)

    Karatas, Ali F; Bober, Michael B; Rogers, Kenneth; Duker, Angela L; Ditro, Colleen P; Mackenzie, William G

    2014-09-01

    Majewski osteodysplastic primordial dwarfism type II (MOPDII) is characterized by severe prenatal and postnatal growth failure with microcephaly, characteristic skeletal dysplasia, an increased risk for cerebrovascular disease, and insulin resistance. MOPDII is caused by mutations in the pericentrin (PCNT) gene and is inherited in an autosomal-recessive manner. This study aimed to determine the incidence of hip pathology in patients with molecularly confirmed MOPDII and to describe the functional outcomes of surgical treatment. Thirty-three enrolled patients had a clinical diagnosis of MOPDII. Biallelic PCNT mutations or absent pericentrin protein was confirmed in 25 of these patients. Twelve patients (7 female) had appropriate clinical and radiographic records at this institution and were included in this study. The data collected included age at presentation, age at surgery, sex, body weight and height, weight-bearing status at diagnosis, and the clinical examination. Four patients (31%) had coxa vara: 3 unilateral and 1 bilateral. Three unilateral patients had in situ pinning at a mean age 4 years. The patient with bilateral coxa vara had valgus osteotomy at the age of 5 years. Two children had bilateral hip dysplasia and subluxation with no surgery. One patient had bilateral developmental hip dislocations. The patient was treated by open reduction-spica cast and 2 years after surgery, coxa valga was noted. Another patient was diagnosed at an age of 12 years with bilateral avascular necrosis of the hips. Four patients did not have hip pathology. Hip pathology is common among children with MOPDII; coxa vara is the most frequent diagnosis. Routine clinical and radiographic hip evaluation is important. The capital femoral epiphysis appears to slip down along the shaft, giving the appearance of a proximal femoral epiphysiolysis. A hip diagnosed with slipped capital femoral epiphysis in early life may progress to severe coxa vara. Level IV.

  9. Psychosocial dwarfism: psychopathological aspects and putative neuroendocrine markers.

    Science.gov (United States)

    Muñoz-Hoyos, Antonio; Molina-Carballo, Antonio; Augustin-Morales, Maríadelcarmen; Contreras-Chova, Francisco; Naranjo-Gómez, Ana; Justicia-Martínez, Fuensanta; Uberos, José

    2011-06-30

    There exists an extensive terminology for defining the situation of children who, in varying circumstances, suffer from affective deprivation (AD), within an unsatisfactory family situation or in institutions. Nevertheless, the neuroendocrine mechanisms (if they exist) determining it have yet to be identified. Our objective was to determine if specific neuroendocrine markers, all of them previously implicated in affective disorders, could be modified, and in which sense, in affective deprivation syndrome of the child. For this purpose, we studied three separate groups of children: (1) control group (CG); (2) children suffering from AD; and (3) children with non-organic failure to thrive (NOFT). In every case, we studied the serum levels of melatonin, serotonin, β-endorphins and adrenocorticotropic hormone (ACTH); and kynurenine pathway tryptophan metabolites (both during the day and at night). Significantly, there was a conspicuous reduction in the levels of each of the neuroendocrine markers (melatonin, serotonin, β-endorphins and ACTH) in the group suffering from affective deficiency, a diminution which was even more noticeable in the group of patients presenting delayed growth. Furthermore, as also occurs in other affective disorders, there were corresponding modifications in the metabolisation of tryptophan. We report the existence of neuroendocrine mechanisms that are associated with the above-mentioned clinical manifestations in these patients, mechanisms that may underlie the close connection existing between AD syndrome and the cause of NOFT. These data suggest that the AD syndrome and NOFT comprise a single process, but one with a different evolutionary continuum of psychosocial dwarfism. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. A novel two-step method for screening shade tolerant mutant plants via dwarfism

    Science.gov (United States)

    When subjected to shade, plants undergo rapid shoot elongation, which often makes them more prone to disease and mechanical damage. It has been reported that, in turfgrass, induced dwarfism can enhance shade tolerance. Here, we describe a two-step procedure for isolating shade tolerant mutants of ...

  11. Novel Microcephalic Primordial Dwarfism Disorder Associated with Variants in the Centrosomal Protein Ninein

    DEFF Research Database (Denmark)

    Dauber, Andrew; LaFranchi, Stephen H.; Maliga, Zoltan

    2012-01-01

    Context: Microcephalic primordial dwarfism (MPD) is a rare, severe form of human growth failure in which growth restriction is evident in utero and continues into postnatal life. Single causative gene defects have been identified in a number of patients with MPD, and all involve genes fundamental...

  12. Meier-Gorlin syndrome: Growth and secondary sexual development of a microcephalic primordial dwarfism disorder

    NARCIS (Netherlands)

    Munnik, S.A. de; Otten, B.J.; Schoots, J.; Bicknell, L.S.; Aftimos, S.; Al-Aama, J.Y.; Bever, Y. van; Bober, M.B.; Borm, G.F.; Clayton-Smith, J.; Deal, C.L.; Edrees, A.Y.; Feingold, M.; Fryer, A.; Hagen, J.M. van; Hennekam, R.C.M.; Jansweijer, M.C.E.; Johnson, D.; Kant, S.G.; Opitz, J.M.; Ramadevi, A.R.; Reardon, W.; Ross, A.; Sarda, P.; Schrander-Stumpel, C.T.R.M.; Sluiter, A.E.; Temple, I.K.; Terhal, P.A.; Toutain, A.; Wise, C.A.; Wright, M.; Skidmore, D.L.; Samuels, M.E.; Hoefsloot, L.H.; Knoers, N.V.A.M.; Brunner, H.G.; Jackson, A.P.; Bongers, M.H.F.

    2012-01-01

    Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by primordial dwarfism, microtia, and patellar aplasia/hypoplasia. Recently, mutations in the ORC1, ORC4, ORC6, CDT1, and CDC6 genes, encoding components of the pre-replication complex, have been identified. This

  13. De Novo GMNN Mutations Cause Autosomal-Dominant Primordial Dwarfism Associated with Meier-Gorlin Syndrome

    NARCIS (Netherlands)

    Burrage, L.C.; Charng, W.L.; Eldomery, M.K.; Willer, J.R.; Davis, E.E.; Lugtenberg, D.; Zhu, W.; Leduc, M.S.; Akdemir, Z.C.; Azamian, M.; Zapata, G.; Hernandez, P.P.; Schoots, J.; Munnik, S.A. de; Roepman, R.; Pearring, J.N.; Jhangiani, S.; Katsanis, N.; Vissers, L.E.L.M.; Brunner, H.G.; Beaudet, A.L.; Rosenfeld, J.A.; Muzny, D.M.; Gibbs, R.A.; Eng, C.M.; Xia, F.; Lalani, S.R.; Lupski, J.R.; Bongers, E.M.H.F.; Yang, Y

    2015-01-01

    Meier-Gorlin syndrome (MGS) is a genetically heterogeneous primordial dwarfism syndrome known to be caused by biallelic loss-of-function mutations in one of five genes encoding pre-replication complex proteins: ORC1, ORC4, ORC6, CDT1, and CDC6. Mutations in these genes cause disruption of the origin

  14. Intrauterine dwarfism, peculiar facies and thin bones with multiple fractures - a new syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kozlowski, K.; Kan, A.

    1988-07-01

    Three newborns with thin ribs and thin long bones with multiple fractures are reported. Whereas one patient presents a syndromic association of bone dysplasia and intrauterine dwarfism two other patients cannot be appropriately evaluated due to lack of basic clinical and pathologic data.

  15. A truncated F-box protein confers the dwarfism in cucumber

    Science.gov (United States)

    Dwarfism is an important plant architecture trait for cucumber breeding. In the present study, we identified a dwarf mutant 406M in cucumber which showed a shorter internode length as compared with its wild type. In a BC1F2 population from the cross of 406M with its wild type parental line 406, the ...

  16. Morphometrics and behavior of a wild Asian elephant exhibiting disproportionate dwarfism.

    Science.gov (United States)

    de Silva, Shermin; Weerathunga, U Sameera; Pushpakumara, Tennekoon V

    2014-12-19

    Dwarfism is a condition characterized by shorter stature, at times accompanied by differential skeletal growth proportions relative to the species-typical physical conformation. Causes vary and are well-documented in humans as well as certain mammalian species in captive or laboratory conditions, but rarely observed in the wild. We report on a single case of apparent dwarfism in a free-ranging adult male Asian elephant in Sri Lanka, comparing physical dimensions to those of other males in the population as well as in previous literature. The subject M459 was found to have a shoulder height of approximately 195 cm, is shorter than the average height of typical mature males, with a body length of 218 cm. This ratio of body length to height deviates from what is typically observed, which is approximately 1:1, but was similar to the attributes of a dwarf elephant in captivity documented in 1955. We report on behavior including the surprising observation that M459 appears to have a competitive advantage in intrasexual contests. We discuss how this phenotype compares to cases of dwarfism in other non-human animals. M459 exemplifies a rare occurrence of disproportionate dwarfism in a free-ranging wild mammal that has survived to reproductive maturity and appears otherwise healthy.

  17. Deletion in the EVC2 Gene Causes Chondrodysplastic Dwarfism in Tyrolean Grey Cattle

    Science.gov (United States)

    Murgiano, Leonardo; Jagannathan, Vidhya; Benazzi, Cinzia; Bolcato, Marilena; Brunetti, Barbara; Muscatello, Luisa Vera; Dittmer, Keren; Piffer, Christian; Gentile, Arcangelo; Drögemüller, Cord

    2014-01-01

    During the summer of 2013 seven Italian Tyrolean Grey calves were born with abnormally short limbs. Detailed clinical and pathological examination revealed similarities to chondrodysplastic dwarfism. Pedigree analysis showed a common founder, assuming autosomal monogenic recessive transmission of the defective allele. A positional cloning approach combining genome wide association and homozygosity mapping identified a single 1.6 Mb genomic region on BTA 6 that was associated with the disease. Whole genome re-sequencing of an affected calf revealed a single candidate causal mutation in the Ellis van Creveld syndrome 2 (EVC2) gene. This gene is known to be associated with chondrodysplastic dwarfism in Japanese Brown cattle, and dwarfism, abnormal nails and teeth, and dysostosis in humans with Ellis-van Creveld syndrome. Sanger sequencing confirmed the presence of a 2 bp deletion in exon 19 (c.2993_2994ACdel) that led to a premature stop codon in the coding sequence of bovine EVC2, and was concordant with the recessive pattern of inheritance in affected and carrier animals. This loss of function mutation confirms the important role of EVC2 in bone development. Genetic testing can now be used to eliminate this form of chondrodysplastic dwarfism from Tyrolean Grey cattle. PMID:24733244

  18. Genome-wide SNP association-based localization of a dwarfism gene in Friesian dwarf horses

    NARCIS (Netherlands)

    Orr, J.L.; Back, W.; Gu, J.; Leegwater, P.H.; Govindarajan, P.; Conroy, J.; Ducro, B.J.; Arendonk, van J.A.M.

    2010-01-01

    The recent completion of the horse genome and commercial availability of an equine SNP genotyping array has facilitated the mapping of disease genes. We report putative localization of the gene responsible for dwarfism, a trait in Friesian horses that is thought to have a recessive mode of

  19. TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism.

    Science.gov (United States)

    Harley, Margaret E; Murina, Olga; Leitch, Andrea; Higgs, Martin R; Bicknell, Louise S; Yigit, Gökhan; Blackford, Andrew N; Zlatanou, Anastasia; Mackenzie, Karen J; Reddy, Kaalak; Halachev, Mihail; McGlasson, Sarah; Reijns, Martin A M; Fluteau, Adeline; Martin, Carol-Anne; Sabbioneda, Simone; Elcioglu, Nursel H; Altmüller, Janine; Thiele, Holger; Greenhalgh, Lynn; Chessa, Luciana; Maghnie, Mohamad; Salim, Mahmoud; Bober, Michael B; Nürnberg, Peter; Jackson, Stephen P; Hurles, Matthew E; Wollnik, Bernd; Stewart, Grant S; Jackson, Andrew P

    2016-01-01

    DNA lesions encountered by replicative polymerases threaten genome stability and cell cycle progression. Here we report the identification of mutations in TRAIP, encoding an E3 RING ubiquitin ligase, in patients with microcephalic primordial dwarfism. We establish that TRAIP relocalizes to sites of DNA damage, where it is required for optimal phosphorylation of H2AX and RPA2 during S-phase in response to ultraviolet (UV) irradiation, as well as fork progression through UV-induced DNA lesions. TRAIP is necessary for efficient cell cycle progression and mutations in TRAIP therefore limit cellular proliferation, providing a potential mechanism for microcephaly and dwarfism phenotypes. Human genetics thus identifies TRAIP as a component of the DNA damage response to replication-blocking DNA lesions.

  20. [Mutation analysis of FGFR3 gene in a family featuring hereditary dwarfism].

    Science.gov (United States)

    Zhang, Qiong; Jiang, Hai-ou; Quan, Qing-li; Li, Jun; He, Ting; Huang, Xue-shuang

    2011-12-01

    To investigate the clinical symptoms and potential mutation in FGFR3 gene for a family featuring hereditary dwarfism in order to attain diagnosis and provide prenatal diagnosis. Five patients and two unaffected relatives from the family, in addition with 100 healthy controls, were recruited. Genome DNA was extracted. Exons 10 and 13 of the FGFR3 gene were amplified using polymerase chain reaction (PCR). PCR products were sequenced in both directions. All patients had similar features including short stature, short limbs, lumbar hyperlordosis but normal craniofacial features. A heterozygous mutation G1620T (N540K) was identified in the cDNA from all patients but not in the unaffected relatives and 100 control subjects. A heterozygous G380R mutation was excluded. The hereditary dwarfism featured by this family has been caused by hypochondroplasia (HCH) due to a N540K mutation in the FGFR3 gene.

  1. Skeletal dysplasia with craniofacial deformity and disproportionate dwarfism in hair sheep of northeastern Brazil.

    Science.gov (United States)

    Dantas, F P M; Medeiros, G X; Figueiredo, A P M; Thompson, K; Riet-Correa, F

    2014-01-01

    This paper reports a newly described form of skeletal dysplasia affecting Brazilian hair sheep of the Cabugi breed. This breed is characterized by having a short head and in some cases the animals are smaller and more compact than sheep of similar breeds. Lambs born with craniofacial abnormalities and dwarfism that die at 2-6 months of age are frequent in this breed. In a flock of 68 ewes and three rams of the Cabugi breed, 134 lambs were born over a 4-year period. Of these, 14 (10.4%) had marked cranial abnormalities and dwarfism and died or were humanely destroyed, 43 (32%) had a normal face and 77 (57.5%) had the short face characteristic of the breed. Dwarf lambs were much smaller than normal, with short legs, a domed head with retruded muzzle and protruded mandible, sternal deformities and exophthalmic eyes situated more laterally in the face than normal. Microscopical examination of long bones of the limbs, bones of the base of the skull and vertebrae showed no lesions. Bones from four affected lambs and one control lamb were macerated for morphometric examination. Although the length of the spinal cord was similar, there was disproportionate shortening of the appendicular bones, particularly the distal segments. Thus the disease was defined as a skeletal dysplasia characterized by craniofacial deformity and disproportionate dwarfism. It is suggested that the disease is inherited as an incomplete dominant trait. The shortened face, which is a feature of the Cabugi breed, may represent the heterozygous state and the more severe, often lethal, dwarfism may occur in homozygotes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Pituitary dwarfism in Saarloos and Czechoslovakian wolfdogs is associated with a mutation in LHX3.

    Science.gov (United States)

    Voorbij, A M W Y; Leegwater, P A; Kooistra, H S

    2014-01-01

    Pituitary dwarfism in German Shepherd Dogs is associated with autosomal recessive inheritance and a mutation in LHX3, resulting in combined pituitary hormone deficiency. Congenital dwarfism also is encountered in breeds related to German Shepherd Dogs, such as Saarloos and Czechoslovakian wolfdogs. To investigate whether Saarloos and Czechoslovakian wolfdog dwarfs have the same LHX3 mutation as do Germans Shepherd Dog dwarfs. A specific aim was to determine the carrier frequency among Saarloos and Czechoslovakian wolfdogs used for breeding. Two client-owned Saarloos wolfdogs and 4 client-owned Czechoslovakian wolfdogs with pituitary dwarfism, 239 clinically healthy client-owned Saarloos wolfdogs, and 200 client-owned clinically healthy Czechoslovakian wolfdogs. Genomic DNA was amplified using polymerase chain reaction (PCR). In the Saarloos and Czechoslovakian wolfdog dwarfs, PCR products were analyzed by sequencing. DNA fragment length analysis was performed on the samples from the clinically healthy dogs. Saarloos and Czechoslovakian wolfdog dwarfs have the same 7 bp deletion in intron 5 of LHX3 as do German Shepherd Dog dwarfs. The frequency of carriers of this mutation among clinically healthy Saarloos and Czechoslovakian wolfdogs used for breeding was 31% and 21%, respectively. An LHX3 mutation is associated with pituitary dwarfism in Saarloos and Czechoslovakian wolfdogs. The rather high frequency of carriers of the mutated gene in the 2 breeds emphasizes the need for screening before breeding. If all breeding animals were genetically tested for the presence of the LHX3 mutation and a correct breeding policy would be implemented, this disease could be eradicated completely. Copyright © 2014 by the American College of Veterinary Internal Medicine.

  3. A frameshift mutation in GON4L is associated with proportionate dwarfism in Fleckvieh cattle.

    Science.gov (United States)

    Schwarzenbacher, Hermann; Wurmser, Christine; Flisikowski, Krzysztof; Misurova, Lubica; Jung, Simone; Langenmayer, Martin C; Schnieke, Angelika; Knubben-Schweizer, Gabriela; Fries, Ruedi; Pausch, Hubert

    2016-03-31

    Low birth weight and postnatal growth restriction are the most evident symptoms of dwarfism. Accompanying skeletal aberrations may compromise the general condition and locomotion of affected individuals. Several paternal half-sibs with a low birth weight and a small size were born in 2013 in the Fleckvieh cattle population. Affected calves were strikingly underweight at birth in spite of a normal gestation length and had craniofacial abnormalities such as elongated narrow heads and brachygnathia inferior. In spite of a normal general condition, their growth remained restricted during rearing. We genotyped 27 affected and 10,454 unaffected animals at 44,672 single nucleotide polymorphisms and performed association tests followed by homozygosity mapping, which allowed us to map the locus responsible for growth failure to a 1.85-Mb segment on bovine chromosome 3. Analysis of whole-genome re-sequencing data from one affected and 289 unaffected animals revealed a 1-bp deletion (g.15079217delC, rs723240647) in the coding region of the GON4L gene that segregated with the dwarfism-associated haplotype. We showed that the deletion induces intron retention and premature termination of translation, which can lead to a severely truncated protein that lacks domains that are likely essential to normal protein function. The widespread use of an undetected carrier bull for artificial insemination has resulted in a tenfold increase in the frequency of the deleterious allele in the female population. A frameshift mutation in GON4L is associated with autosomal recessive proportionate dwarfism in Fleckvieh cattle. The mutation has segregated in the population for more than 50 years without being recognized as a genetic disorder. However, the widespread use of an undetected carrier bull for artificial insemination caused a sudden accumulation of homozygous calves with dwarfism. Our findings provide the basis for genome-based mating strategies to avoid the inadvertent mating of carrier

  4. Total knee arthroplasty in a pseudoachondroplastic dwarfism patient with bilateral patellar dislocation.

    Science.gov (United States)

    Oh, Kwang-Jun; Yoon, Jung-Ro; Yang, Jae-Hyuk

    2013-01-01

    Late presentation of congenital patellar dislocation with advanced osteoarthritis is rare. This article presents a case of a 59-year-old man with underlying pseudoachondroplastic dwarfism. Advanced osteoarthritis due to bilateral neglected congenital patellar dislocation was treated with total knee arthroplasty without patella relocation surgery. Two years later, the patient had an improvement in Knee Society scores, painless function, and stability. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Hypomorphism in human NSMCE2 linked to primordial dwarfism and insulin resistance.

    Science.gov (United States)

    Payne, Felicity; Colnaghi, Rita; Rocha, Nuno; Seth, Asha; Harris, Julie; Carpenter, Gillian; Bottomley, William E; Wheeler, Eleanor; Wong, Stephen; Saudek, Vladimir; Savage, David; O'Rahilly, Stephen; Carel, Jean-Claude; Barroso, Inês; O'Driscoll, Mark; Semple, Robert

    2014-09-01

    Structural maintenance of chromosomes (SMC) complexes are essential for maintaining chromatin structure and regulating gene expression. Two the three known SMC complexes, cohesin and condensin, are important for sister chromatid cohesion and condensation, respectively; however, the function of the third complex, SMC5-6, which includes the E3 SUMO-ligase NSMCE2 (also widely known as MMS21) is less clear. Here, we characterized 2 patients with primordial dwarfism, extreme insulin resistance, and gonadal failure and identified compound heterozygous frameshift mutations in NSMCE2. Both mutations reduced NSMCE2 expression in patient cells. Primary cells from one patient showed increased micronucleus and nucleoplasmic bridge formation, delayed recovery of DNA synthesis, and reduced formation of foci containing Bloom syndrome helicase (BLM) after hydroxyurea-induced replication fork stalling. These nuclear abnormalities in patient dermal fibroblast were restored by expression of WT NSMCE2, but not a mutant form lacking SUMO-ligase activity. Furthermore, in zebrafish, knockdown of the NSMCE2 ortholog produced dwarfism, which was ameliorated by reexpression of WT, but not SUMO-ligase-deficient NSMCE. Collectively, these findings support a role for NSMCE2 in recovery from DNA damage and raise the possibility that loss of its function produces dwarfism through reduced tolerance of replicative stress.

  6. Genome-wide SNP association-based localization of a dwarfism gene in Friesian dwarf horses.

    Science.gov (United States)

    Orr, N; Back, W; Gu, J; Leegwater, P; Govindarajan, P; Conroy, J; Ducro, B; Van Arendonk, J A M; MacHugh, D E; Ennis, S; Hill, E W; Brama, P A J

    2010-12-01

    The recent completion of the horse genome and commercial availability of an equine SNP genotyping array has facilitated the mapping of disease genes. We report putative localization of the gene responsible for dwarfism, a trait in Friesian horses that is thought to have a recessive mode of inheritance, to a 2-MB region of chromosome 14 using just 10 affected animals and 10 controls. We successfully genotyped 34,429 SNPs that were tested for association with dwarfism using chi-square tests. The most significant SNP in our study, BIEC2-239376 (P(2df)=4.54 × 10(-5), P(rec)=7.74 × 10(-6)), is located close to a gene implicated in human dwarfism. Fine-mapping and resequencing analyses did not aid in further localization of the causative variant, and replication of our findings in independent sample sets will be necessary to confirm these results. © 2010 The Authors, Journal compilation © 2010 Stichting International Foundation for Animal Genetics.

  7. Lateral retroperitoneal transpsoas interbody fusion in a patient with achondroplastic dwarfism.

    Science.gov (United States)

    Staub, Blake N; Holman, Paul J

    2015-02-01

    The authors present the first reported use of the lateral retroperitoneal transpsoas approach for interbody arthrodesis in a patient with achondroplastic dwarfism. The inherent anatomical abnormalities of the spine present in achondroplastic dwarfism predispose these patients to an increased incidence of spinal deformity as well as neurogenic claudication and potential radicular symptoms. The risks associated with prolonged general anesthesia and intolerance of significant blood loss in these patients makes them ideal candidates for minimally invasive spinal surgery. The patient in this case was a 51-year-old man with achondroplastic dwarfism who had a history of progressive claudication and radicular pain despite previous extensive lumbar laminectomies. The lateral retroperitoneal transpsoas approach was used for placement of interbody cages at L1/2, L2/3, L3/4, and L4/5, followed by posterior decompression and pedicle screw instrumentation. The patient tolerated the procedure well with no complications. Postoperatively his claudicatory and radicular symptoms resolved and a CT scan revealed solid arthrodesis with no periimplant lucencies.

  8. Insular dwarfism in hippos and a model for brain size reduction in Homo floresiensis.

    Science.gov (United States)

    Weston, Eleanor M; Lister, Adrian M

    2009-05-07

    Body size reduction in mammals is usually associated with only moderate brain size reduction, because the brain and sensory organs complete their growth before the rest of the body during ontogeny. On this basis, 'phyletic dwarfs' are predicted to have a greater relative brain size than 'phyletic giants'. However, this trend has been questioned in the special case of dwarfism of mammals on islands. Here we show that the endocranial capacities of extinct dwarf species of hippopotamus from Madagascar are up to 30% smaller than those of a mainland African ancestor scaled to equivalent body mass. These results show that brain size reduction is much greater than predicted from an intraspecific 'late ontogenetic' model of dwarfism in which brain size scales to body size with an exponent of 0.35. The nature of the proportional change or grade shift observed here indicates that selective pressures on brain size are potentially independent of those on body size. This study demonstrates empirically that it is mechanistically possible for dwarf mammals on islands to evolve significantly smaller brains than would be predicted from a model of dwarfing based on the intraspecific scaling of the mainland ancestor. Our findings challenge current understanding of brain-body allometric relationships in mammals and suggest that the process of dwarfism could in principle explain small brain size, a factor relevant to the interpretation of the small-brained hominin found on the Island of Flores, Indonesia.

  9. Bulldog dwarfism in Dexter cattle is caused by mutations in ACAN.

    Science.gov (United States)

    Cavanagh, Julie A L; Tammen, Imke; Windsor, Peter A; Bateman, John F; Savarirayan, Ravi; Nicholas, Frank W; Raadsma, Herman W

    2007-11-01

    Bulldog dwarfism in Dexter cattle is one of the earliest single-locus disorders described in animals. Affected fetuses display extreme disproportionate dwarfism, reflecting abnormal cartilage development (chondrodysplasia). Typically, they die around the seventh month of gestation, precipitating a natural abortion. Heterozygotes show a milder form of dwarfism, most noticeably having shorter legs. Homozygosity mapping in candidate regions in a small Dexter pedigree suggested aggrecan (ACAN) as the most likely candidate gene. Mutation screening revealed a 4-bp insertion in exon 11 (2266_2267insGGCA) (called BD1 for diagnostic testing) and a second, rarer transition in exon 1 (-198C>T) (called BD2) that cosegregate with the disorder. In chondrocytes from cattle heterozygous for the insertion, mutant mRNA is subject to nonsense-mediated decay, showing only 8% of normal expression. Genotyping in Dexter families throughout the world shows a one-to-one correspondence between genotype and phenotype at this locus. The heterozygous and homozygous-affected Dexter cattle could prove invaluable as a model for human disorders caused by mutations in ACAN.

  10. Two novel POC1A mutations in the primordial dwarfism, SOFT syndrome: Clinical homogeneity but also unreported malformations.

    Science.gov (United States)

    Barraza-García, Jimena; Iván Rivera-Pedroza, Carlos; Salamanca, Luis; Belinchón, Alberta; López-González, Vanesa; Sentchordi-Montané, Lucía; del Pozo, Ángela; Santos-Simarro, Fernando; Campos-Barros, Ángel; Lapunzina, Pablo; Guillén-Navarro, Encarna; González-Casado, Isabel; García-Miñaur, Sixto; Heath, Karen E

    2016-01-01

    Primordial dwarfism encompasses rare conditions characterized by severe intrauterine growth retardation and growth deficiency throughout life. Recently, three POC1A mutations have been reported in six families with the primordial dwarfism, SOFT syndrome (Short stature, Onychodysplasia, Facial dysmorphism, and hypoTrichosis). Using a custom-designed Next-generation sequencing skeletal dysplasia panel, we have identified two novel homozygous POC1A mutations in two individuals with primordial dwarfism. The severe growth retardation and the facial profiles are strikingly similar between our patients and those described previously. However, one of our patients was diagnosed with severe foramen magnum stenosis and subglottic tracheal stenosis, malformations not previously associated with this syndrome. Our findings confirm that POC1A mutations cause SOFT syndrome and that mutations in this gene should be considered in patients with severe pre- and postnatal short stature, symmetric shortening of long bones, triangular facies, sparse hair and short, thickened distal phalanges. © 2015 Wiley Periodicals, Inc.

  11. A COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism.

    Directory of Open Access Journals (Sweden)

    Mirjam Frischknecht

    Full Text Available We describe a mild form of disproportionate dwarfism in Labrador Retrievers, which is not associated with any obvious health problems such as secondary arthrosis. We designate this phenotype as skeletal dysplasia 2 (SD2. It is inherited as a monogenic autosomal recessive trait with incomplete penetrance primarily in working lines of the Labrador Retriever breed. Using 23 cases and 37 controls we mapped the causative mutation by genome-wide association and homozygosity mapping to a 4.44 Mb interval on chromosome 12. We re-sequenced the genome of one affected dog at 30x coverage and detected 92 non-synonymous variants in the critical interval. Only two of these variants, located in the lymphotoxin A (LTA and collagen alpha-2(XI chain gene (COL11A2, respectively, were perfectly associated with the trait. Previously described COL11A2 variants in humans or mice lead to skeletal dysplasias and/or deafness. The dog variant associated with disproportionate dwarfism, COL11A2:c.143G>C or p.R48P, probably has only a minor effect on collagen XI function, which might explain the comparatively mild phenotype seen in our study. The identification of this candidate causative mutation thus widens the known phenotypic spectrum of COL11A2 mutations. We speculate that non-pathogenic COL11A2 variants might even contribute to the heritable variation in height.

  12. Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism.

    Science.gov (United States)

    Reynolds, John J; Bicknell, Louise S; Carroll, Paula; Higgs, Martin R; Shaheen, Ranad; Murray, Jennie E; Papadopoulos, Dimitrios K; Leitch, Andrea; Murina, Olga; Tarnauskaitė, Žygimantė; Wessel, Sarah R; Zlatanou, Anastasia; Vernet, Audrey; von Kriegsheim, Alex; Mottram, Rachel M A; Logan, Clare V; Bye, Hannah; Li, Yun; Brean, Alexander; Maddirevula, Sateesh; Challis, Rachel C; Skouloudaki, Kassiani; Almoisheer, Agaadir; Alsaif, Hessa S; Amar, Ariella; Prescott, Natalie J; Bober, Michael B; Duker, Angela; Faqeih, Eissa; Seidahmed, Mohammed Zain; Al Tala, Saeed; Alswaid, Abdulrahman; Ahmed, Saleem; Al-Aama, Jumana Yousuf; Altmüller, Janine; Al Balwi, Mohammed; Brady, Angela F; Chessa, Luciana; Cox, Helen; Fischetto, Rita; Heller, Raoul; Henderson, Bertram D; Hobson, Emma; Nürnberg, Peter; Percin, E Ferda; Peron, Angela; Spaccini, Luigina; Quigley, Alan J; Thakur, Seema; Wise, Carol A; Yoon, Grace; Alnemer, Maha; Tomancak, Pavel; Yigit, Gökhan; Taylor, A Malcolm R; Reijns, Martin A M; Simpson, Michael A; Cortez, David; Alkuraya, Fowzan S; Mathew, Christopher G; Jackson, Andrew P; Stewart, Grant S

    2017-04-01

    To ensure efficient genome duplication, cells have evolved numerous factors that promote unperturbed DNA replication and protect, repair and restart damaged forks. Here we identify downstream neighbor of SON (DONSON) as a novel fork protection factor and report biallelic DONSON mutations in 29 individuals with microcephalic dwarfism. We demonstrate that DONSON is a replisome component that stabilizes forks during genome replication. Loss of DONSON leads to severe replication-associated DNA damage arising from nucleolytic cleavage of stalled replication forks. Furthermore, ATM- and Rad3-related (ATR)-dependent signaling in response to replication stress is impaired in DONSON-deficient cells, resulting in decreased checkpoint activity and the potentiation of chromosomal instability. Hypomorphic mutations in DONSON substantially reduce DONSON protein levels and impair fork stability in cells from patients, consistent with defective DNA replication underlying the disease phenotype. In summary, we have identified mutations in DONSON as a common cause of microcephalic dwarfism and established DONSON as a critical replication fork protein required for mammalian DNA replication and genome stability.

  13. Laron Dwarfism and Non-Insulin-Dependent Diabetes Mellitus in the Hnf-1α Knockout Mouse

    Science.gov (United States)

    Lee, Ying-Hue; Sauer, Brian; Gonzalez, Frank J.

    1998-01-01

    Mice deficient in hepatocyte nuclear factor 1 alpha (HNF-1α) were produced by use of the Cre-loxP recombination system. HNF-1α-null mice are viable but sterile and exhibit a phenotype reminiscent of both Laron-type dwarfism and non-insulin-dependent diabetes mellitus (NIDDM). In contrast to an earlier HNF-1α-null mouse line that had been produced by use of standard gene disruption methodology (M. Pontoglio, J. Barra, M. Hadchouel, A. Doyen, C. Kress, J. P. Bach, C. Babinet, and M. Yaniv, Cell 84:575–585, 1996), these mice exhibited no increased mortality and only minimal renal dysfunction during the first 6 months of development. Both dwarfism and NIDDM are most likely due to the loss of expression of insulin-like growth factor I (IGF-I) and lower levels of insulin, resulting in stunted growth and elevated serum glucose levels, respectively. These results confirm the functional significance of the HNF-1α regulatory elements that had previously been shown to reside in the promoter regions of both the IGF-I and the insulin genes. PMID:9566924

  14. A COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism.

    Science.gov (United States)

    Frischknecht, Mirjam; Niehof-Oellers, Helena; Jagannathan, Vidhya; Owczarek-Lipska, Marta; Drögemüller, Cord; Dietschi, Elisabeth; Dolf, Gaudenz; Tellhelm, Bernd; Lang, Johann; Tiira, Katriina; Lohi, Hannes; Leeb, Tosso

    2013-01-01

    We describe a mild form of disproportionate dwarfism in Labrador Retrievers, which is not associated with any obvious health problems such as secondary arthrosis. We designate this phenotype as skeletal dysplasia 2 (SD2). It is inherited as a monogenic autosomal recessive trait with incomplete penetrance primarily in working lines of the Labrador Retriever breed. Using 23 cases and 37 controls we mapped the causative mutation by genome-wide association and homozygosity mapping to a 4.44 Mb interval on chromosome 12. We re-sequenced the genome of one affected dog at 30x coverage and detected 92 non-synonymous variants in the critical interval. Only two of these variants, located in the lymphotoxin A (LTA) and collagen alpha-2(XI) chain gene (COL11A2), respectively, were perfectly associated with the trait. Previously described COL11A2 variants in humans or mice lead to skeletal dysplasias and/or deafness. The dog variant associated with disproportionate dwarfism, COL11A2:c.143G>C or p.R48P, probably has only a minor effect on collagen XI function, which might explain the comparatively mild phenotype seen in our study. The identification of this candidate causative mutation thus widens the known phenotypic spectrum of COL11A2 mutations. We speculate that non-pathogenic COL11A2 variants might even contribute to the heritable variation in height.

  15. Phylogeographic and population genetic analyses reveal multiple species of Boa and independent origins of insular dwarfism.

    Science.gov (United States)

    Card, Daren C; Schield, Drew R; Adams, Richard H; Corbin, Andrew B; Perry, Blair W; Andrew, Audra L; Pasquesi, Giulia I M; Smith, Eric N; Jezkova, Tereza; Boback, Scott M; Booth, Warren; Castoe, Todd A

    2016-09-01

    Boa is a Neotropical genus of snakes historically recognized as monotypic despite its expansive distribution. The distinct morphological traits and color patterns exhibited by these snakes, together with the wide diversity of ecosystems they inhabit, collectively suggest that the genus may represent multiple species. Morphological variation within Boa also includes instances of dwarfism observed in multiple offshore island populations. Despite this substantial diversity, the systematics of the genus Boa has received little attention until very recently. In this study we examined the genetic structure and phylogenetic relationships of Boa populations using mitochondrial sequences and genome-wide SNP data obtained from RADseq. We analyzed these data at multiple geographic scales using a combination of phylogenetic inference (including coalescent-based species delimitation) and population genetic analyses. We identified extensive population structure across the range of the genus Boa and multiple lines of evidence for three widely-distributed clades roughly corresponding with the three primary land masses of the Western Hemisphere. We also find both mitochondrial and nuclear support for independent origins and parallel evolution of dwarfism on offshore island clusters in Belize and Cayos Cochinos Menor, Honduras. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Dwarfism and early death in mice lacking C-type natriuretic peptide

    Science.gov (United States)

    Chusho, Hideki; Tamura, Naohisa; Ogawa, Yoshihiro; Yasoda, Akihiro; Suda, Michio; Miyazawa, Takashi; Nakamura, Kenji; Nakao, Kazuki; Kurihara, Tatsuya; Komatsu, Yasato; Itoh, Hiroshi; Tanaka, Kiyoshi; Saito, Yoshihiko; Katsuki, Motoya; Nakao, Kazuwa

    2001-01-01

    Longitudinal bone growth is determined by endochondral ossification that occurs as chondrocytes in the cartilaginous growth plate undergo proliferation, hypertrophy, cell death, and osteoblastic replacement. The natriuretic peptide family consists of three structurally related endogenous ligands, atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP), and is thought to be involved in a variety of homeostatic processes. To investigate the physiological significance of CNP in vivo, we generated mice with targeted disruption of CNP (Nppc−/− mice). The Nppc−/− mice show severe dwarfism as a result of impaired endochondral ossification. They are all viable perinatally, but less than half can survive during postnatal development. The skeletal phenotypes are histologically similar to those seen in patients with achondroplasia, the most common genetic form of human dwarfism. Targeted expression of CNP in the growth plate chondrocytes can rescue the skeletal defect of Nppc−/− mice and allow their prolonged survival. This study demonstrates that CNP acts locally as a positive regulator of endochondral ossification in vivo and suggests its pathophysiological and therapeutic implication in some forms of skeletal dysplasia. PMID:11259675

  17. MAJEWSKI OSTEODYSPLASTIC PRIMORDIAL DWARFISM TYPE II: CLINICAL FINDINGS AND DENTAL MANAGEMENT OF A CHILD PATIENT

    Directory of Open Access Journals (Sweden)

    Arslan Terlemez

    2015-01-01

    Full Text Available Majewski osteodysplastic primordial dwarfism type II (MOPD II is an unusual autosomal recessive inherited form of primordial dwarfism, which is characterized by a small head diameter at birth, but which also progresses to severe microcephaly, progressive bony dysplasia, and characteristic facies and personality. This report presents a case of a five-year-old girl with MOPD II syndrome. The patient was referred to our clinic with the complaint of severe tooth pain at the left mandibular primary molar teeth. Clinical examination revealed that most of the primary teeth had been decayed and all primary teeth were hypoplastic. Patient’s history revealed delayed development in the primary dentition and radiographic examination showed rootless primary molar teeth and short-rooted incisors. The treatment was not possible due to the lack of root of the left mandibular primary molars; so the teeth were extracted. Thorough and timely dental evaluation is crucial for the prevention of dental problems and the maintenance of oral health in patients with MOPD II syndrome is of utmost importance.

  18. Dwarfism with joint laxity in Friesian horses is associated with a splice site mutation in B4GALT7

    NARCIS (Netherlands)

    Leegwater, Peter A.; Vos-Loohuis, Manon; Ducro, Bart J.; Boegheim, Iris J.; Bastiaansen, John W.M.; Dibbits, Bert W.; Schurink, Anouk

    2016-01-01

    Background: Inbreeding and population bottlenecks in the ancestry of Friesian horses has led to health issues such as dwarfism. The limbs of dwarfs are short and the ribs are protruding inwards at the costochondral junction, while the head and back appear normal. A striking feature of the

  19. Dwarfism with joint laxity in Friesian horses is associated with a splice site mutation in B4GALT7

    NARCIS (Netherlands)

    Leegwater, Peter A; Vos-Loohuis, Manon; Ducro, Bart J; Boegheim, Iris J; van Steenbeek, Frank G; Nijman, Isaac J; Monroe, Glen R; Bastiaansen, John W M; Dibbits, Bert W; van de Goor, Leanne H; Hellinga, Ids; Back, Willem; Schurink, Anouk

    2016-01-01

    BACKGROUND: Inbreeding and population bottlenecks in the ancestry of Friesian horses has led to health issues such as dwarfism. The limbs of dwarfs are short and the ribs are protruding inwards at the costochondral junction, while the head and back appear normal. A striking feature of the condition

  20. Influence of the social context on use of surgical-lengthening and group-empowering coping strategies among people with dwarfism.

    Science.gov (United States)

    Fernández, Saulo; Branscombe, Nyla R; Gómez, Angel; Morales, J Francisco

    2012-08-01

    To assess the role that social contextual factors exert on the way people with disproportionate short stature (dwarfism) cope with the negative consequences of discrimination. Using multigroup structural equation modeling, we compare the coping process of people with dwarfism from Spain (N = 63) and the USA (N = 145), two countries that differ in the role played by organizations offering support to people with dwarfism. In Spain, where organizational support is recent, a coping approach aimed at achieving integration with the majority group through limb-lengthening surgery prevails; in the USA, where the long-standing organization of people with dwarfism encourages pride in being a "little person" and positive intragroup contact, a coping strategy based on empowering the minority group dominates. Both strategies, each in its own context, are effective at protecting psychological well-being from the negative consequences of stigmatization; however, they exert their positive effects through different processes.

  1. Bone structure in two adult subjects with impaired minor spliceosome function resulting from RNU4ATAC mutations causing microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1)

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Frost, Morten; Larsen, Martin Jakob

    2016-01-01

    Microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1), or Taybi-Linder syndrome is characterized by distinctive skeletal dysplasia, severe intrauterine and postnatal growth retardation, microcephaly, dysmorphic features, and neurological malformations. It is an autosomal recessive...

  2. Radiological findings in the hand in Seckel syndrome (bird-headed dwarfism)

    Energy Technology Data Exchange (ETDEWEB)

    Poznanski, A.K.; Iannaccone, G.; Pasquino, A.M.; Boscherini, B.

    1983-02-01

    Two patients with severe intrauterine growth retardation and bird-headed appearance are described. These two children had most of the clinical features of the so-called Seckel dwarfism. The radiological findings included: (1) ivory epiphyses affecting all phalanges in one patient and many phalanges in another; (2) cone-shaped epiphyses in the proximal phalanges; (3) marked disharmonic bone maturation between carpals and phalanges, between individual carpals, and from side to side; (4) alteration in the length of the hand bones, with considerable similarity of the metacarpophalangeal pattern between the two children; (5) relatively small carpals, which have an angular configuration; and (6) relatively normal or increased cortical thickness of the metacarpals.

  3. Pregnancy Outcome in Cartilage-Hair Hypoplasia, a Rare Form of Dwarfism

    Science.gov (United States)

    Thavarajah, Harshithaa

    2017-01-01

    Background. This case report discusses the pregnancy outcome of a patient with cartilage-hair hypoplasia, a rare form of dwarfism, and multiple previous orthopedic surgeries. Literature on pregnancy outcomes in patients with cartilage-hair hypoplasia is limited. Case. A 32-year-old patient with cartilage-hair hypoplasia presented at 12 weeks' gestation to the high-risk obstetrics clinic for care. Preterm labor resulted in cesarean delivery at 34 weeks' gestation with general anesthetic. Breastfeeding was stopped at 6 weeks due to neonatal complications. Conclusion. Pregnancy and delivery were uncomplicated. A multidisciplinary approach allowed for effective management during pregnancy and postnatal care. This is the first known documented case of prenatal care, delivery, and breastfeeding in a woman with this rare disorder. PMID:28251002

  4. POC1A truncation mutation causes a ciliopathy in humans characterized by primordial dwarfism.

    Science.gov (United States)

    Shaheen, Ranad; Faqeih, Eissa; Shamseldin, Hanan E; Noche, Ramil R; Sunker, Asma; Alshammari, Muneera J; Al-Sheddi, Tarfa; Adly, Nouran; Al-Dosari, Mohammed S; Megason, Sean G; Al-Husain, Muneera; Al-Mohanna, Futwan; Alkuraya, Fowzan S

    2012-08-10

    Primordial dwarfism (PD) is a phenotype characterized by profound growth retardation that is prenatal in onset. Significant strides have been made in the last few years toward improved understanding of the molecular underpinning of the limited growth that characterizes the embryonic and postnatal development of PD individuals. These include impaired mitotic mechanics, abnormal IGF2 expression, perturbed DNA-damage response, defective spliceosomal machinery, and abnormal replication licensing. In three families affected by a distinct form of PD, we identified a founder truncating mutation in POC1A. This gene is one of two vertebrate paralogs of POC1, which encodes one of the most abundant proteins in the Chlamydomonas centriole proteome. Cells derived from the index individual have abnormal mitotic mechanics with multipolar spindles, in addition to clearly impaired ciliogenesis. siRNA knockdown of POC1A in fibroblast cells recapitulates this ciliogenesis defect. Our findings highlight a human ciliopathy syndrome caused by deficiency of a major centriolar protein.

  5. Paleopathological Study of Dwarfism-Related Skeletal Dysplasia in a Late Joseon Dynasty (South Korean) Population.

    Science.gov (United States)

    Woo, Eun Jin; Lee, Won-Joon; Hu, Kyung-Seok; Hwang, Jae Joon

    2015-01-01

    Skeletal dysplasias related to genetic etiologies have rarely been reported for past populations. This report presents the skeletal characteristics of an individual with dwarfism-related skeletal dysplasia from South Korea. To assess abnormal deformities, morphological features, metric data, and computed tomography scans are analyzed. Differential diagnoses include achondroplasia or hypochondroplasia, chondrodysplasia, multiple epiphyseal dysplasia, thalassemia-related hemolytic anemia, and lysosomal storage disease. The diffused deformities in the upper-limb bones and several coarsened features of the craniofacial bones indicate the most likely diagnosis to have been a certain type of lysosomal storage disease. The skeletal remains of EP-III-4-No.107 from the Eunpyeong site, although incomplete and fragmented, provide important clues to the paleopathological diagnosis of skeletal dysplasias.

  6. Pregnancy Outcome in Cartilage-Hair Hypoplasia, a Rare Form of Dwarfism

    Directory of Open Access Journals (Sweden)

    Harshithaa Thavarajah

    2017-01-01

    Full Text Available Background. This case report discusses the pregnancy outcome of a patient with cartilage-hair hypoplasia, a rare form of dwarfism, and multiple previous orthopedic surgeries. Literature on pregnancy outcomes in patients with cartilage-hair hypoplasia is limited. Case. A 32-year-old patient with cartilage-hair hypoplasia presented at 12 weeks’ gestation to the high-risk obstetrics clinic for care. Preterm labor resulted in cesarean delivery at 34 weeks’ gestation with general anesthetic. Breastfeeding was stopped at 6 weeks due to neonatal complications. Conclusion. Pregnancy and delivery were uncomplicated. A multidisciplinary approach allowed for effective management during pregnancy and postnatal care. This is the first known documented case of prenatal care, delivery, and breastfeeding in a woman with this rare disorder.

  7. Multiple intracranial aneurysms and moyamoya disease associated with microcephalic osteodysplastic primordial dwarfism type II: surgical considerations.

    Science.gov (United States)

    Waldron, James S; Hetts, Steven W; Armstrong-Wells, Jennifer; Dowd, Christopher F; Fullerton, Heather J; Gupta, Nalin; Lawton, Michael T

    2009-11-01

    Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a rare genetic syndrome characterized by extremely small stature and microcephaly, and is associated in 25% of patients with intracranial aneurysms and moyamoya disease. Although aneurysmal subarachnoid hemorrhage and stroke are leading causes of morbidity and death in these patients, MOPD II is rarely examined in the neurosurgical literature. The authors report their experience with 3 patients who presented with MOPD II, which includes a patient with 8 aneurysms (the most aneurysms reported in the literature), and the first report of a patient with both moyamoya disease and multiple aneurysms. The poor natural history of these lesions indicates aggressive microsurgical and/or endovascular therapy. Microsurgery, whether for aneurysm clip placement or extracranial-intracranial bypass, is challenging due to tight surgical corridors and diminutive arteries in these patients, but is technically feasible and strongly indicated when multiple aneurysms must be treated or cerebral revascularization is needed.

  8. Mandible shape and dwarfism in squirrels (Mammalia, Rodentia): interaction of allometry and adaptation

    Science.gov (United States)

    Hautier, Lionel; Fabre, Pierre-Henri; Michaux, Jacques

    2009-06-01

    Squirrels include several independent lineages of dwarf forms distributed into two ecological groups: the dwarf tree and flying squirrels. The mandible of dwarf tree squirrels share a highly reduced coronoid process and a condylar process drawn backwards. Dwarf flying squirrels on the other hand, have an elongated coronoid process and a well-differentiated condylar process. To interpret such a difference, Elliptic Fourier Transform was used to evaluate how mandible shape varies with dwarfism in sciurids. The results obtained show that this clear-cut difference cannot be explained by a simple allometric relationship in relation with size decrease. We concluded that the retention of anteriorly positioned eye sockets, in relation with distance estimation, allowed the conservation of a well-differentiated coronoid process in all flying species, despite the trend towards its reduction observed among sciurids as their size decreases.

  9. Microcephalic osteodysplastic primordial dwarfism type I with biallelic mutations in the RNU4ATAC gene.

    Science.gov (United States)

    Nagy, R; Wang, H; Albrecht, B; Wieczorek, D; Gillessen-Kaesbach, G; Haan, E; Meinecke, P; de la Chapelle, A; Westman, J A

    2012-08-01

    Microcephalic osteodysplastic primordial dwarfism type I (MOPD I) is a rare autosomal recessive developmental disorder characterized by extreme intrauterine growth retardation, severe microcephaly, central nervous system abnormalities, dysmorphic facial features, skin abnormalities, skeletal changes, limb deformations, and early death. Recently, mutations in the RNU4ATAC gene, which encodes U4atac, a small nuclear RNA that is a crucial component of the minor spliceosome, were found to cause MOPD I. MOPD I is the first disease known to be associated with a defect in small nuclear RNAs. We describe here the clinical and molecular data for 17 cases of MOPD I, including 15 previously unreported cases, all carrying biallelic mutations in the RNU4ATAC gene. © 2011 John Wiley & Sons A/S.

  10. Dwarfism and age-associated spinal degeneration of heterozygote cmd mice defective in aggrecan

    Science.gov (United States)

    Watanabe, Hideto; Nakata, Ken; Kimata, Koji; Nakanishi, Isao; Yamada, Yoshihiko

    1997-01-01

    Mouse cartilage matrix deficiency (cmd) is an autosomal recessive disorder caused by a genetic defect of aggrecan, a large chondroitin sulfate proteoglycan in cartilage. The homozygotes (−/−) are characterized by cleft palate and short limbs, tail, and snout. They die just after birth because of respiratory failure, and the heterozygotes (+/−) appear normal at birth. Here we report that the heterozygotes show dwarfism and develop spinal misalignment with age. Within 19 months of age, they exhibit spastic gait caused by misalignment of the cervical spine and die because of starvation. Histological examination revealed a high incidence of herniation and degeneration of vertebral discs. Electron microscopy showed a degeneration of disc chondrocytes in the heterozygotes. These findings may facilitate the identification of mutations in humans predisposed to spinal degeneration. PMID:9192671

  11. The collagen receptor DDR2 regulates proliferation and its elimination leads to dwarfism.

    Science.gov (United States)

    Labrador, J P; Azcoitia, V; Tuckermann, J; Lin, C; Olaso, E; Mañes, S; Brückner, K; Goergen, J L; Lemke, G; Yancopoulos, G; Angel, P; Martínez, C; Klein, R

    2001-05-01

    The discoidin domain receptor 2 (DDR2) is a member of a subfamily of receptor tyrosine kinases whose ligands are fibrillar collagens, and is widely expressed in postnatal tissues. We have generated DDR2-deficient mice to establish the in vivo functions of this receptor, which have remained obscure. These mice exhibit dwarfism and shortening of long bones. This phenotype appears to be caused by reduced chondrocyte proliferation, rather than aberrant differentiation or function. In a skin wound healing model, DDR2-/- mice exhibit a reduced proliferative response compared with wild-type littermates. In vitro, fibroblasts derived from DDR2-/- mutants proliferate more slowly than wild-type fibroblasts, a defect that is rescued by introduction of wild-type but not kinase-dead DDR2 receptor. Together our results suggest that DDR2 acts as an extracellular matrix sensor to modulate cell proliferation.

  12. Adaptive stress response in segmental progeria resembles long-lived dwarfism and calorie restriction in mice.

    Directory of Open Access Journals (Sweden)

    Marieke van de Ven

    2006-12-01

    Full Text Available How congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular senescence is a likely contributing mechanism. Contrary to expectations, neither accelerated senescence nor acute oxidative stress hypersensitivity was detected in primary fibroblast or erythroblast cultures from multiple progeroid mouse models for defects in the nucleotide excision DNA repair pathway, which share premature aging features including postnatal growth retardation, cerebellar ataxia, and death before weaning. Instead, we report a prominent phenotypic overlap with long-lived dwarfism and calorie restriction during postnatal development (2 wk of age, including reduced size, reduced body temperature, hypoglycemia, and perturbation of the growth hormone/insulin-like growth factor 1 neuroendocrine axis. These symptoms were also present at 2 wk of age in a novel progeroid nucleotide excision repair-deficient mouse model (XPD(G602D/R722W/XPA(-/- that survived weaning with high penetrance. However, despite persistent cachectic dwarfism, blood glucose and serum insulin-like growth factor 1 levels returned to normal by 10 wk, with hypoglycemia reappearing near premature death at 5 mo of age. These data strongly suggest changes in energy metabolism as part of an adaptive response during the stressful period of postnatal growth. Interestingly, a similar perturbation of the postnatal growth axis was not detected in another progeroid mouse model, the double-strand DNA break repair deficient Ku80(-/- mouse. Specific (but not all types of genome instability may thus engage a conserved response to stress that evolved to cope with environmental pressures such as food shortage.

  13. Adaptive stress response in segmental progeria resembles long-lived dwarfism and calorie restriction in mice.

    Science.gov (United States)

    van de Ven, Marieke; Andressoo, Jaan-Olle; Holcomb, Valerie B; von Lindern, Marieke; Jong, Willeke M C; De Zeeuw, Chris I; Suh, Yousin; Hasty, Paul; Hoeijmakers, Jan H J; van der Horst, Gijsbertus T J; Mitchell, James R

    2006-12-15

    How congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular senescence is a likely contributing mechanism. Contrary to expectations, neither accelerated senescence nor acute oxidative stress hypersensitivity was detected in primary fibroblast or erythroblast cultures from multiple progeroid mouse models for defects in the nucleotide excision DNA repair pathway, which share premature aging features including postnatal growth retardation, cerebellar ataxia, and death before weaning. Instead, we report a prominent phenotypic overlap with long-lived dwarfism and calorie restriction during postnatal development (2 wk of age), including reduced size, reduced body temperature, hypoglycemia, and perturbation of the growth hormone/insulin-like growth factor 1 neuroendocrine axis. These symptoms were also present at 2 wk of age in a novel progeroid nucleotide excision repair-deficient mouse model (XPD(G602D/R722W)/XPA(-/-)) that survived weaning with high penetrance. However, despite persistent cachectic dwarfism, blood glucose and serum insulin-like growth factor 1 levels returned to normal by 10 wk, with hypoglycemia reappearing near premature death at 5 mo of age. These data strongly suggest changes in energy metabolism as part of an adaptive response during the stressful period of postnatal growth. Interestingly, a similar perturbation of the postnatal growth axis was not detected in another progeroid mouse model, the double-strand DNA break repair deficient Ku80(-/-) mouse. Specific (but not all) types of genome instability may thus engage a conserved response to stress that evolved to cope with environmental pressures such as food shortage.

  14. A Novel Two-Step Method for Screening Shade Tolerant Mutant Plants via Dwarfism

    Science.gov (United States)

    Li, Wei; Katin-Grazzini, Lorenzo; Krishnan, Sanalkumar; Thammina, Chandra; El-Tanbouly, Rania; Yer, Huseyin; Merewitz, Emily; Guillard, Karl; Inguagiato, John; McAvoy, Richard J.; Liu, Zongrang; Li, Yi

    2016-01-01

    When subjected to shade, plants undergo rapid shoot elongation, which often makes them more prone to disease and mechanical damage. Shade-tolerant plants can be difficult to breed; however, they offer a substantial benefit over other varieties in low-light areas. Although perennial ryegrass (Lolium perenne L.) is a popular species of turf grasses because of their good appearance and fast establishment, the plant normally does not perform well under shade conditions. It has been reported that, in turfgrass, induced dwarfism can enhance shade tolerance. Here we describe a two-step procedure for isolating shade tolerant mutants of perennial ryegrass by first screening for dominant dwarf mutants, and then screening dwarf plants for shade tolerance. The two-step screening process to isolate shade tolerant mutants can be done efficiently with limited space at early seedling stages, which enables quick and efficient isolation of shade tolerant mutants, and thus facilitates development of shade tolerant new cultivars of turfgrasses. Using the method, we isolated 136 dwarf mutants from 300,000 mutagenized seeds, with 65 being shade tolerant (0.022%). When screened directly for shade tolerance, we recovered only four mutants from a population of 150,000 (0.003%) mutagenized seeds. One shade tolerant mutant, shadow-1, was characterized in detail. In addition to dwarfism, shadow-1 and its sexual progeny displayed high degrees of tolerance to both natural and artificial shade. We showed that endogenous gibberellin (GA) content in shadow-1 was higher than wild-type controls, and shadow-1 was also partially GA insensitive. Our novel, simple and effective two-step screening method should be applicable to breeding shade tolerant cultivars of turfgrasses, ground covers, and other economically important crop plants that can be used under canopies of existing vegetation to increase productivity per unit area of land. PMID:27752260

  15. A Novel Two-Step Method for Screening Shade Tolerant Mutant Plants via Dwarfism.

    Science.gov (United States)

    Li, Wei; Katin-Grazzini, Lorenzo; Krishnan, Sanalkumar; Thammina, Chandra; El-Tanbouly, Rania; Yer, Huseyin; Merewitz, Emily; Guillard, Karl; Inguagiato, John; McAvoy, Richard J; Liu, Zongrang; Li, Yi

    2016-01-01

    When subjected to shade, plants undergo rapid shoot elongation, which often makes them more prone to disease and mechanical damage. Shade-tolerant plants can be difficult to breed; however, they offer a substantial benefit over other varieties in low-light areas. Although perennial ryegrass (Lolium perenne L.) is a popular species of turf grasses because of their good appearance and fast establishment, the plant normally does not perform well under shade conditions. It has been reported that, in turfgrass, induced dwarfism can enhance shade tolerance. Here we describe a two-step procedure for isolating shade tolerant mutants of perennial ryegrass by first screening for dominant dwarf mutants, and then screening dwarf plants for shade tolerance. The two-step screening process to isolate shade tolerant mutants can be done efficiently with limited space at early seedling stages, which enables quick and efficient isolation of shade tolerant mutants, and thus facilitates development of shade tolerant new cultivars of turfgrasses. Using the method, we isolated 136 dwarf mutants from 300,000 mutagenized seeds, with 65 being shade tolerant (0.022%). When screened directly for shade tolerance, we recovered only four mutants from a population of 150,000 (0.003%) mutagenized seeds. One shade tolerant mutant, shadow-1, was characterized in detail. In addition to dwarfism, shadow-1 and its sexual progeny displayed high degrees of tolerance to both natural and artificial shade. We showed that endogenous gibberellin (GA) content in shadow-1 was higher than wild-type controls, and shadow-1 was also partially GA insensitive. Our novel, simple and effective two-step screening method should be applicable to breeding shade tolerant cultivars of turfgrasses, ground covers, and other economically important crop plants that can be used under canopies of existing vegetation to increase productivity per unit area of land.

  16. Growth in individuals with Majewski osteodysplastic primordial dwarfism type II caused by pericentrin mutations.

    Science.gov (United States)

    Bober, Michael B; Niiler, Tim; Duker, Angela L; Murray, Jennie E; Ketterer, Tara; Harley, Margaret E; Alvi, Sabah; Flora, Christina; Rustad, Cecilie; Bongers, Ernie M H F; Bicknell, Louise S; Wise, Carol; Jackson, Andrew P

    2012-11-01

    Microcephalic primordial dwarfism (MPD) is a class of disorders characterized by intrauterine growth restriction (IUGR), impaired postnatal growth and microcephaly. Majewski osteodysplastic primordial dwarfism type II (MOPD II) is one of the more common conditions within this group. MOPD II is caused by truncating mutations in pericentrin (PCNT) and is inherited in an autosomal recessive manner. Detailed growth curves for length, weight, and OFC are presented here and derived from retrospective data from 26 individuals with MOPD II confirmed by molecular or functional studies. Severe pre- and postnatal growth failure is evident in MOPD II patients. The length, weight, and OFC at term (when corrected for gestational age) were -7.0, -3.9, and -4.6 standard deviation (SD) below the population mean and equivalent to the 50th centile of a 28-29-, 31-32-, and 30-31-week neonate, respectively. While at skeletal maturity, the height, weight, and OFC were -10.3, -14.3, and -8.5 SD below the population mean and equivalent to the size of 3-year 10- to 11-month-old, a 5-year 2- to 3-month-old, and 5- to 6-month-old, respectively. During childhood, MOPD II patients grow with slowed, but fairly constant growth velocities and show no evidence of any pubertal growth spurt. Treatment with human growth hormone (n = 11) did not lead to any significant improvement in final stature. The growth charts presented here will be of assistance with diagnosis and management of MOPD II, and should have particular utility in nutritional management of MOPD II during infancy. Copyright © 2012 Wiley Periodicals, Inc.

  17. Mutations in CENPE define a novel kinetochore-centromeric mechanism for microcephalic primordial dwarfism.

    Science.gov (United States)

    Mirzaa, Ghayda M; Vitre, Benjamin; Carpenter, Gillian; Abramowicz, Iga; Gleeson, Joseph G; Paciorkowski, Alex R; Cleveland, Don W; Dobyns, William B; O'Driscoll, Mark

    2014-08-01

    Defects in centrosome, centrosomal-associated and spindle-associated proteins are the most frequent cause of primary microcephaly (PM) and microcephalic primordial dwarfism (MPD) syndromes in humans. Mitotic progression and segregation defects, microtubule spindle abnormalities and impaired DNA damage-induced G2-M cell cycle checkpoint proficiency have been documented in cell lines from these patients. This suggests that impaired mitotic entry, progression and exit strongly contribute to PM and MPD. Considering the vast protein networks involved in coordinating this cell cycle stage, the list of potential target genes that could underlie novel developmental disorders is large. One such complex network, with a direct microtubule-mediated physical connection to the centrosome, is the kinetochore. This centromeric-associated structure nucleates microtubule attachments onto mitotic chromosomes. Here, we described novel compound heterozygous variants in CENPE in two siblings who exhibit a profound MPD associated with developmental delay, simplified gyri and other isolated abnormalities. CENPE encodes centromere-associated protein E (CENP-E), a core kinetochore component functioning to mediate chromosome congression initially of misaligned chromosomes and in subsequent spindle microtubule capture during mitosis. Firstly, we present a comprehensive clinical description of these patients. Then, using patient cells we document abnormalities in spindle microtubule organization, mitotic progression and segregation, before modeling the cellular pathogenicity of these variants in an independent cell system. Our cellular analysis shows that a pathogenic defect in CENP-E, a kinetochore-core protein, largely phenocopies PCNT-mutated microcephalic osteodysplastic primordial dwarfism-type II patient cells. PCNT encodes a centrosome-associated protein. These results highlight a common underlying pathomechanism. Our findings provide the first evidence for a kinetochore-based route to

  18. Conditional Expression of Wnt4 during Chondrogenesis Leads to Dwarfism in Mice

    Science.gov (United States)

    Lee, Hu-Hui; Behringer, Richard R.

    2007-01-01

    Wnts are expressed in the forming long bones, suggesting roles in skeletogenesis. To examine the action of Wnts in skeleton formation, we developed a genetic system to conditionally express Wnt4 in chondrogenic tissues of the mouse. A mouse Wnt4 cDNA was introduced into the ubiquitously expressed Rosa26 (R26) locus by gene targeting in embryonic stem (ES) cells. The expression of Wnt4 from the R26 locus was blocked by a neomycin selection cassette flanked by loxP sites (floxneo) that was positioned between the Rosa26 promoter and the Wnt4 cDNA, creating the allele designated R26floxneoWnt4. Wnt4 expression was activated during chondrogenesis using Col2a1-Cre transgenic mice that express Cre recombinase in differentiating chondrocytes. R26floxneoWnt4; Col2a1-Cre double heterozygous mice exhibited a growth deficiency, beginning approximately 7 to 10 days after birth, that resulted in dwarfism. In addition, they also had craniofacial abnormalities, and delayed ossification of the lumbar vertebrae and pelvic bones. Histological analysis revealed a disruption in the organization of the growth plates and a delay in the onset of the primary and secondary ossification centers. Molecular studies showed that Wnt4 overexpression caused decreased proliferation and altered maturation of chondrocytes. In addition, R26floxneoWnt4; Col2a1-Cre mice had decreased expression of vascular endothelial growth factor (VEGF). These studies demonstrate that Wnt4 overexpression leads to dwarfism in mice. The data indicate that Wnt4 levels must be regulated in chondrocytes for normal growth plate development and skeletogenesis. Decreased VEGF expression suggests that defects in vascularization may contribute to the dwarf phenotype. PMID:17505543

  19. Adaptive Stress Response in Segmental Progeria Resembles Long-Lived Dwarfism and Calorie Restriction in Mice

    Science.gov (United States)

    Holcomb, Valerie B; von Lindern, Marieke; Jong, Willeke M. C; Zeeuw, Chris I. De; Suh, Yousin; Hasty, Paul; Hoeijmakers, Jan H. J; van der Horst, Gijsbertus T. J; Mitchell, James R

    2006-01-01

    How congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular senescence is a likely contributing mechanism. Contrary to expectations, neither accelerated senescence nor acute oxidative stress hypersensitivity was detected in primary fibroblast or erythroblast cultures from multiple progeroid mouse models for defects in the nucleotide excision DNA repair pathway, which share premature aging features including postnatal growth retardation, cerebellar ataxia, and death before weaning. Instead, we report a prominent phenotypic overlap with long-lived dwarfism and calorie restriction during postnatal development (2 wk of age), including reduced size, reduced body temperature, hypoglycemia, and perturbation of the growth hormone/insulin-like growth factor 1 neuroendocrine axis. These symptoms were also present at 2 wk of age in a novel progeroid nucleotide excision repair-deficient mouse model (XPDG602D/R722W/XPA−/−) that survived weaning with high penetrance. However, despite persistent cachectic dwarfism, blood glucose and serum insulin-like growth factor 1 levels returned to normal by 10 wk, with hypoglycemia reappearing near premature death at 5 mo of age. These data strongly suggest changes in energy metabolism as part of an adaptive response during the stressful period of postnatal growth. Interestingly, a similar perturbation of the postnatal growth axis was not detected in another progeroid mouse model, the double-strand DNA break repair deficient Ku80 −/− mouse. Specific (but not all) types of genome instability may thus engage a conserved response to stress that evolved to cope with environmental pressures such as food shortage. PMID:17173483

  20. Conditional expression of Wnt4 during chondrogenesis leads to dwarfism in mice.

    Directory of Open Access Journals (Sweden)

    Hu-Hui Lee

    Full Text Available Wnts are expressed in the forming long bones, suggesting roles in skeletogenesis. To examine the action of Wnts in skeleton formation, we developed a genetic system to conditionally express Wnt4 in chondrogenic tissues of the mouse. A mouse Wnt4 cDNA was introduced into the ubiquitously expressed Rosa26 (R26 locus by gene targeting in embryonic stem (ES cells. The expression of Wnt4 from the R26 locus was blocked by a neomycin selection cassette flanked by loxP sites (floxneo that was positioned between the Rosa26 promoter and the Wnt4 cDNA, creating the allele designated R26(floxneoWnt4. Wnt4 expression was activated during chondrogenesis using Col2a1-Cre transgenic mice that express Cre recombinase in differentiating chondrocytes. R26(floxneoWnt4; Col2a1-Cre double heterozygous mice exhibited a growth deficiency, beginning approximately 7 to 10 days after birth, that resulted in dwarfism. In addition, they also had craniofacial abnormalities, and delayed ossification of the lumbar vertebrae and pelvic bones. Histological analysis revealed a disruption in the organization of the growth plates and a delay in the onset of the primary and secondary ossification centers. Molecular studies showed that Wnt4 overexpression caused decreased proliferation and altered maturation of chondrocytes. In addition, R26(floxneoWnt4; Col2a1-Cre mice had decreased expression of vascular endothelial growth factor (VEGF. These studies demonstrate that Wnt4 overexpression leads to dwarfism in mice. The data indicate that Wnt4 levels must be regulated in chondrocytes for normal growth plate development and skeletogenesis. Decreased VEGF expression suggests that defects in vascularization may contribute to the dwarf phenotype.

  1. Dwarfism of blue mussels in the low saline Baltic Sea — growth to the lower salinity limit

    DEFF Research Database (Denmark)

    Riisgård, Hans Ulrik; Larsen, Poul Scheel; Turja, Raisa

    2014-01-01

    Mussels within the Baltic Mytilus edulis × M. trossulus hybrid zone have adapted to the low salinities in the Baltic Sea which, however, results in slow-growing dwarfed mussels. To get a better understanding of the nature of dwarfism, we studied the ability of M. trossulus to feed and grow at low...... to become negative below 4.5 psu. We suggest that reduced ability to produce shell material at extremely low salinity may explain dwarfism of mussels in the Baltic Sea. Reduced bio-calcification at low salinity, however, may impede shell growth, but not somatic growth, and this may at first result...... in an increased condition index, as seen in the benthic Baltic Sea mussels transferred to cages suspended in the water column....

  2. A nonsense mutation in cGMP-dependent type II protein kinase (PRKG2) causes dwarfism in American Angus cattle.

    Science.gov (United States)

    Koltes, James E; Mishra, Bishnu P; Kumar, Dinesh; Kataria, Ranjit S; Totir, Liviu R; Fernando, Rohan L; Cobbold, Rowland; Steffen, David; Coppieters, Wouter; Georges, Michel; Reecy, James M

    2009-11-17

    Historically, dwarfism was the major genetic defect in U.S. beef cattle. Aggressive culling and sire testing were used to minimize its prevalence; however, neither of these practices can eliminate a recessive genetic defect. We assembled a 4-generation pedigree to identify the mutation underlying dwarfism in American Angus cattle. An adaptation of the Elston-Steward algorithm was used to overcome small pedigree size and missing genotypes. The dwarfism locus was fine-mapped to BTA6 between markers AFR227 and BM4311. Four candidate genes were sequenced, revealing a nonsense mutation in exon 15 of cGMP-dependant type II protein kinase (PRKG2). This C/T transition introduced a stop codon (R678X) that truncated 85 C-terminal amino acids, including a large portion of the kinase domain. Of the 75 mutations discovered in this region, only this mutation was 100% concordant with the recessive pattern of inheritance in affected and carrier individuals (log of odds score = 6.63). Previous research has shown that PRKG2 regulates SRY (sex-determining region Y) box 9 (SOX9)-mediated transcription of collagen 2 (COL2). We evaluated the ability of wild-type (WT) or R678X PRKG2 to regulate COL2 expression in cell culture. Real-time PCR results confirmed that COL2 is overexpressed in cells that overexpressed R678X PRKG2 as compared with WT PRKG2. Furthermore, COL2 and COL10 mRNA expression was increased in dwarf cattle compared with unaffected cattle. These experiments indicate that the R678X mutation is functional, resulting in a loss of PRKG2 regulation of COL2 and COL10 mRNA expression. Therefore, we present PRKG2 R678X as a causative mutation for dwarfism cattle.

  3. Elevated Fibroblast Growth Factor Signaling Is Critical for the Pathogenesis of the Dwarfism in Evc2/Limbin Mutant Mice.

    Science.gov (United States)

    Zhang, Honghao; Kamiya, Nobuhiro; Tsuji, Takehito; Takeda, Haruko; Scott, Greg; Rajderkar, Sudha; Ray, Manas K; Mochida, Yoshiyuki; Allen, Benjamin; Lefebvre, Veronique; Hung, Irene H; Ornitz, David M; Kunieda, Tetsuo; Mishina, Yuji

    2016-12-01

    Ellis-van Creveld (EvC) syndrome is a skeletal dysplasia, characterized by short limbs, postaxial polydactyly, and dental abnormalities. EvC syndrome is also categorized as a ciliopathy because of ciliary localization of proteins encoded by the two causative genes, EVC and EVC2 (aka LIMBIN). While recent studies demonstrated important roles for EVC/EVC2 in Hedgehog signaling, there is still little known about the pathophysiological mechanisms underlying the skeletal dysplasia features of EvC patients, and in particular why limb development is affected, but not other aspects of organogenesis that also require Hedgehog signaling. In this report, we comprehensively analyze limb skeletogenesis in Evc2 mutant mice and in cell and tissue cultures derived from these mice. Both in vivo and in vitro data demonstrate elevated Fibroblast Growth Factor (FGF) signaling in Evc2 mutant growth plates, in addition to compromised but not abrogated Hedgehog-PTHrP feedback loop. Elevation of FGF signaling, mainly due to increased Fgf18 expression upon inactivation of Evc2 in the perichondrium, critically contributes to the pathogenesis of limb dwarfism. The limb dwarfism phenotype is partially rescued by inactivation of one allele of Fgf18 in the Evc2 mutant mice. Taken together, our data uncover a novel pathogenic mechanism to understand limb dwarfism in patients with Ellis-van Creveld syndrome.

  4. A novel mutation in the thyroglobulin gene that causes goiter and dwarfism in Wistar Hannover GALAS rats.

    Science.gov (United States)

    Sato, Akira; Abe, Kuniya; Yuzuriha, Misako; Fujii, Sakiko; Takahashi, Naofumi; Hojo, Hitoshi; Teramoto, Shoji; Aoyama, Hiroaki

    2014-04-01

    Outbred stocks of rats have been used extensively in biomedical, pharmaceutical and/or toxicological studies as a model of genetically heterogeneous human populations. One of such stocks is the Wistar Hannover GALAS rat. However, the colony of Wistar Hannover GALAS rat has been suspected of keeping a problematic mutation that manifests two distinct spontaneous abnormalities, goiter and dwarfism, which often confuses study results. We have successfully identified the responsible mutation, a guanine to thymine transversion at the acceptor site (3' end) of intron 6 in the thyroglobulin (Tg) gene (Tgc.749-1G>T), that induces a complete missing of exon 7 from the whole Tg transcript by mating experiments and subsequent molecular analyses. The following observations confirmed that Tgc.749-1G>T/Tgc.749-1G>T homozygotes manifested both dwarfism and goiter, while Tgc.749-1G>T/+ heterozygotes had only a goiter with normal appearance, suggesting that the mutant phenotypes inherit as an autosomal semi-dominant trait. The mutant phenotypes, goiter and dwarfism, mimicked those caused by typical endocrine disrupters attacking the thyroid. Hence a simple and reliable diagnostic methodology has been developed for genomic DNA-based genotyping of animals. The diagnostic methodology reported here would allow users of Wistar Hannover GALAS rats to evaluate their study results precisely by carefully interpreting the data obtained from Tgc.749-1G>T/+ heterozygotes having externally undetectable thyroidal lesions. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Medical management of moyamoya disease and recurrent stroke in an infant with Majewski osteodysplastic primordial dwarfism type II (MOPD II).

    Science.gov (United States)

    Kılıç, Esra; Utine, Eda; Unal, Sule; Haliloğlu, Göknur; Oğuz, Kader Karli; Cetin, Mualla; Boduroğlu, Koray; Alanay, Yasemin

    2012-10-01

    We report an infant diagnosed with Majewski osteodysplastic primordial dwarfism type II at age 8 months, who experienced cerebrovascular morbidities related to this entity. Molecular analysis identified c.2609+1 G>A, intron 14, homozygous splice site mutation in the pericentrin gene. At age 18 months, she developed recurrent strokes and hemiparesis. Brain magnetic resonance imaging and magnetic resonance angiography showed abnormal gyral pattern, cortical acute infarcts, bilateral stenosis of the internal carotid arteries and reduced flow on the cerebral arteries, consistent with moyamoya disease. In Majewski osteodysplastic primordial dwarfism type II, life expectancy is reduced because of high risk of stroke secondary to cerebral vascular anomalies (aneurysms, moyamoya disease). Periodic screening for vascular events is recommended in individuals with Majewski osteodysplastic primordial dwarfism type II every 12-18 months following diagnosis. Our patient was medically managed with low molecular weight heparin followed with aspirin prophylaxis, in addition to carbamazepine and physical rehabilitation. We report an infant with moyamoya disease and recurrent stroke presenting 10 months after diagnosis (at age 18 months), and discuss the outcome of nonsurgical medical management. The presented case is the second youngest case developing stroke and moyamoya disease.

  6. Elevated Fibroblast Growth Factor Signaling Is Critical for the Pathogenesis of the Dwarfism in Evc2/Limbin Mutant Mice.

    Directory of Open Access Journals (Sweden)

    Honghao Zhang

    2016-12-01

    Full Text Available Ellis-van Creveld (EvC syndrome is a skeletal dysplasia, characterized by short limbs, postaxial polydactyly, and dental abnormalities. EvC syndrome is also categorized as a ciliopathy because of ciliary localization of proteins encoded by the two causative genes, EVC and EVC2 (aka LIMBIN. While recent studies demonstrated important roles for EVC/EVC2 in Hedgehog signaling, there is still little known about the pathophysiological mechanisms underlying the skeletal dysplasia features of EvC patients, and in particular why limb development is affected, but not other aspects of organogenesis that also require Hedgehog signaling. In this report, we comprehensively analyze limb skeletogenesis in Evc2 mutant mice and in cell and tissue cultures derived from these mice. Both in vivo and in vitro data demonstrate elevated Fibroblast Growth Factor (FGF signaling in Evc2 mutant growth plates, in addition to compromised but not abrogated Hedgehog-PTHrP feedback loop. Elevation of FGF signaling, mainly due to increased Fgf18 expression upon inactivation of Evc2 in the perichondrium, critically contributes to the pathogenesis of limb dwarfism. The limb dwarfism phenotype is partially rescued by inactivation of one allele of Fgf18 in the Evc2 mutant mice. Taken together, our data uncover a novel pathogenic mechanism to understand limb dwarfism in patients with Ellis-van Creveld syndrome.

  7. Primordial Dwarfism Gene Maintains Lin28 Expression to Safeguard Embryonic Stem Cells from Premature Differentiation

    Directory of Open Access Journals (Sweden)

    Qian Dai

    2014-05-01

    Full Text Available Primordial dwarfism (PD is characterized by global growth failure, both during embryogenesis and postnatally. Loss-of-function germline mutations in La ribonucleoprotein domain family, member 7 (LAPR7 have recently been linked to PD. Paradoxically, LARP7 deficiency was previously assumed to be associated with increased cell growth and proliferation via activation of positive transcription elongation factor b (P-TEFb. Here, we show that Larp7 deficiency likely does not significantly increase P-TEFb activity. We further discover that Larp7 knockdown does not affect pluripotency but instead primes embryonic stem cells (ESCs for differentiation via downregulation of Lin28, a positive regulator of organismal growth. Mechanistically, we show that Larp7 interacts with a poly(A polymerase Star-PAP to maintain Lin28 mRNA stability. We propose that proper regulation of Lin28 and PTEFb is essential for embryonic cells to achieve a sufficient number of cell divisions prior to differentiation and ultimately to maintain proper organismal size.

  8. Morquio disease: the role of cartilage canals in the pathogenesis of chondrogenic dwarfism.

    Science.gov (United States)

    Zustin, Jozef

    2010-12-01

    Chondrogenic dwarfism in Morquio disease (mucopolysaccharidosis IV) has been suggested to be strongly linked to the abnormal lysosomal storage of cartilaginous extracellular matrix waste products within chondrocytes and fibroblasts. The specific genetic defects of enzymes of the keratan sulfate and chondroitin-6-sulfate metabolism have been detected at the molecular level and importantly contributed to the current knowledge on the phenotype of this rare metabolic disorder. However, the pathogenesis of this epiphyseal centered progressive skeletal disease does not seem to be fully explained by the dysfunction of the chondrocyte cytoplasm that presents with vacuolar changes in adult patients. I propose that the accumulation of extracellular matrix degradation product-laden macrophages within epiphyseal cartilage canals during the early postnatal period causes dysregulation in the synchronized process of the neoformation and resorption of the maturing radial growing epiphyses. Similarly, the resorption of pannus tissue following the microtraumatisation of weight-bearing joints and epiphysis-type bones becomes impacted. If the hypothesis is valid, the early pathogenesis in Morquio disease could be because of the inadequate regression of cartilage canals and impaired resorption and restitution of pannus tissue.

  9. Physical Basis behind Achondroplasia, the Most Common Form of Human Dwarfism*

    Science.gov (United States)

    He, Lijuan; Horton, William; Hristova, Kalina

    2010-01-01

    Fibroblast growth factor receptor 3 (FGFR3) is a receptor tyrosine kinase that plays an important role in long bone development. The G380R mutation in FGFR3 transmembrane domain is known as the genetic cause for achondroplasia, the most common form of human dwarfism. Despite many studies, there is no consensus about the exact mechanism underlying the pathology. To gain further understanding into the physical basis behind the disorder, here we measure the activation of wild-type and mutant FGFR3 in mammalian cells using Western blots, and we analyze the activation within the frame of a physical-chemical model describing dimerization, ligand binding, and phosphorylation probabilities within the dimers. The data analysis presented here suggests that the mutation does not increase FGFR3 dimerization, as proposed previously. Instead, FGFR3 activity in achondroplasia is increased due to increased probability for phosphorylation of the unliganded mutant dimers. This finding has implications for the design of targeted molecular treatments for achondroplasia. PMID:20624921

  10. Physical basis behind achondroplasia, the most common form of human dwarfism.

    Science.gov (United States)

    He, Lijuan; Horton, William; Hristova, Kalina

    2010-09-24

    Fibroblast growth factor receptor 3 (FGFR3) is a receptor tyrosine kinase that plays an important role in long bone development. The G380R mutation in FGFR3 transmembrane domain is known as the genetic cause for achondroplasia, the most common form of human dwarfism. Despite many studies, there is no consensus about the exact mechanism underlying the pathology. To gain further understanding into the physical basis behind the disorder, here we measure the activation of wild-type and mutant FGFR3 in mammalian cells using Western blots, and we analyze the activation within the frame of a physical-chemical model describing dimerization, ligand binding, and phosphorylation probabilities within the dimers. The data analysis presented here suggests that the mutation does not increase FGFR3 dimerization, as proposed previously. Instead, FGFR3 activity in achondroplasia is increased due to increased probability for phosphorylation of the unliganded mutant dimers. This finding has implications for the design of targeted molecular treatments for achondroplasia.

  11. Dwarfism and cytochrome P450-mediated C-6 oxidation of plant steroid hormones.

    Science.gov (United States)

    Bishop, G; Nomura, T; Yokota, T; Montoya, T; Castle, J; Harrison, K; Kushiro, T; Kamiya, Y; Yamaguchi, S; Bancos, S; Szatmári, A-M; Szekeres, M

    2006-12-01

    BRs (brassinosteroids) are plant steroid hormones that are essential for normal plant development. The dramatic dwarfism exhibited by mutants in the CYP (cytochrome P450) enzymes involved in BR biosynthesis indicates a role for these hormones in plant growth and development. Since the mid-1990s, collaborative research has been geared towards developing a better understanding of the CYP85 class of CYPs involved in BR biosynthesis in both Arabidopsis and tomato. Some of the most recent observations include the fact that certain CYP85 CYPs catalyse the synthesis of the most bioactive BR, BL (brassinolide). Current evidence suggests that evolution of this function may have occurred independently in different dicotyledonous species. Interestingly, BL accumulates in tomato fruits, highlighting a key role for this hormone in fruit development. At the same time as developing a better understanding of the enzymatic function of these CYPs, we have also carried out experiments towards characterizing where and when these genes are expressed and mechanisms of their regulation. As expected for a hormone involved in growth and development, biosynthetic gene promoter activity is associated with young rapidly growing cells and with fruit development.

  12. Selection of male-sterile and dwarfism genetically modified zoysia japonica through gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Tae Woong; Song, In Ja; Kang, Hong Gyu; Jeong, Ok Cheol; Sun, Hyeon Jin; Ko, Suk Min; Lim, Pyung Ok; Song, Pill Soon; Song, Sung Jun; Lee, Hyo Yeon [Jeju National University, Jeju (Korea, Republic of)

    2010-09-15

    The aim of this study is selection of the male-sterile plant for inhibiting transgene flow through gamma-irradiation ({sup 60}Co) at the pollination and fertilization cycle of herbicide-tolerant genetically modified (GM) zoysiagrass (Zoysia japonica Steud.). High frequencies of plant mutations were obtained about 18% from M{sub 1} generation at the doses (10 to 50 Gy). We also found that some M{sub 1} plants showed male-sterile plants using de-husked seeds and comparison of stainable pollen using KI-I{sub 2} solution. Besides the effects of irradiation on pollination and fertilization cycle, various other mutation like dwarf, cold tolerance, increasing grains and mass were observed. Four of dwarfism plants were selected through comparison of morphological characteristic between control and mutants during 4 years. These results demonstrated that the gamma-irradiation on pollination and fertilization cycle is very effective to induce the various mutations, and the male-sterile mutants are useful for controlling transgene flow and developing of high quality turfgasses.

  13. Small body size and extreme cortical bone remodeling indicate phyletic dwarfism in Magyarosaurus dacus (Sauropoda: Titanosauria).

    Science.gov (United States)

    Stein, Koen; Csiki, Zoltan; Rogers, Kristina Curry; Weishampel, David B; Redelstorff, Ragna; Carballido, Jose L; Sander, P Martin

    2010-05-18

    Sauropods were the largest terrestrial tetrapods (>10(5) kg) in Earth's history and grew at rates that rival those of extant mammals. Magyarosaurus dacus, a titanosaurian sauropod from the Upper Cretaceous (Maastrichtian) of Romania, is known exclusively from small individuals (dwarfism (phyletic nanism) in dinosaurs, but a recent study suggested that the small Romanian titanosaurs actually represent juveniles of a larger-bodied taxon. Here we present strong histological evidence that M. dacus was indeed a dwarf (phyletic nanoid). Bone histological analysis of an ontogenetic series of Magyarosaurus limb bones indicates that even the smallest Magyarosaurus specimens exhibit a bone microstructure identical to fully mature or old individuals of other sauropod taxa. Comparison of histologies with large-bodied sauropods suggests that Magyarosaurus had an extremely reduced growth rate, but had retained high basal metabolic rates typical for sauropods. The uniquely decreased growth rate and diminutive body size in Magyarosaurus were adaptations to life on a Cretaceous island and show that sauropod dinosaurs were not exempt from general ecological principles limiting body size.

  14. RB1CC1 Protein Suppresses Type II Collagen Synthesis in Chondrocytes and Causes Dwarfism*

    Science.gov (United States)

    Nishimura, Ichiro; Chano, Tokuhiro; Kita, Hiroko; Matsusue, Yoshitaka; Okabe, Hidetoshi

    2011-01-01

    RB1-inducible coiled-coil 1 (RB1CC1) functions in various processes, such as cell growth, differentiation, senescence, apoptosis, and autophagy. The conditional transgenic mice with cartilage-specific RB1CC1 excess that were used in the present study were made for the first time by the Cre-loxP system. Cartilage-specific RB1CC1 excess caused dwarfism in mice without causing obvious abnormalities in endochondral ossification and subsequent skeletal development from embryo to adult. In vitro and in vivo analysis revealed that the dwarf phenotype in cartilaginous RB1CC1 excess was induced by reductions in the total amount of cartilage and the number of cartilaginous cells, following suppressions of type II collagen synthesis and Erk1/2 signals. In addition, we have demonstrated that two kinds of SNPs (T-547C and C-468T) in the human RB1CC1 promoter have significant influence on the self-transcriptional level. Accordingly, human genotypic variants of RB1CC1 that either stimulate or inhibit RB1CC1 transcription in vivo may cause body size variations. PMID:22049074

  15. Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment.

    Science.gov (United States)

    Wang, Tina; Tsui, Brian; Kreisberg, Jason F; Robertson, Neil A; Gross, Andrew M; Yu, Michael Ku; Carter, Hannah; Brown-Borg, Holly M; Adams, Peter D; Ideker, Trey

    2017-03-28

    Global but predictable changes impact the DNA methylome as we age, acting as a type of molecular clock. This clock can be hastened by conditions that decrease lifespan, raising the question of whether it can also be slowed, for example, by conditions that increase lifespan. Mice are particularly appealing organisms for studies of mammalian aging; however, epigenetic clocks have thus far been formulated only in humans. We first examined whether mice and humans experience similar patterns of change in the methylome with age. We found moderate conservation of CpG sites for which methylation is altered with age, with both species showing an increase in methylome disorder during aging. Based on this analysis, we formulated an epigenetic-aging model in mice using the liver methylomes of 107 mice from 0.2 to 26.0 months old. To examine whether epigenetic aging signatures are slowed by longevity-promoting interventions, we analyzed 28 additional methylomes from mice subjected to lifespan-extending conditions, including Prop1(df/df) dwarfism, calorie restriction or dietary rapamycin. We found that mice treated with these lifespan-extending interventions were significantly younger in epigenetic age than their untreated, wild-type age-matched controls. This study shows that lifespan-extending conditions can slow molecular changes associated with an epigenetic clock in mice livers.

  16. Neuronal migration disorders in microcephalic osteodysplastic primordial dwarfism type I/III.

    Science.gov (United States)

    Juric-Sekhar, Gordana; Kapur, Raj P; Glass, Ian A; Murray, Mitzi L; Parnell, Shawn E; Hevner, Robert F

    2011-04-01

    Microcephalic osteodysplastic primordial dwarfism (MOPD) is a rare microlissencephaly syndrome, with at least two distinct phenotypic and genetic types. MOPD type II is caused by pericentrin mutations, while types I and III appear to represent a distinct entity (MOPD I/III) with variably penetrant phenotypes and unknown genetic basis. The neuropathology of MOPD I/III is little understood, especially in comparison to other forms of lissencephaly. Here, we report postmortem brain findings in an 11-month-old female infant with MOPD I/III. The cerebral cortex was diffusely pachygyric, with a right parietal porencephalic lesion. Histologically, the cortex was abnormally thick and disorganized. Distinct malformations were observed in different cerebral lobes, as characterized using layer-specific neuronal markers. Frontal cortex was severely disorganized and coated with extensive leptomeningeal glioneuronal heterotopia. Temporal cortex had a relatively normal 6-layered pattern, despite cortical thickening. Occipital cortex was variably affected. The corpus callosum was extremely hypoplastic. Brainstem and cerebellar malformations were also present, as well as old necrotic foci. Findings in this case suggest that the cortical malformation in MOPD I/III is distinct from other forms of pachygyria-lissencephaly.

  17. Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) with multiple vascular complications misdiagnosed as Dubowitz syndrome.

    Science.gov (United States)

    Dieks, Jana-Katharina; Baumer, Alessandra; Wilichowski, Ekkehard; Rauch, Anita; Sigler, Matthias

    2014-09-01

    To date, the genetic basis of Dubowitz syndrome (short stature, microcephaly, facial abnormalities, eczema) is unknown and vascular complications are not known to be associated with this syndrome. In microcephalic osteodysplastic primordial dwarfism type II (MOPD II; disproportionate short statue, microcephaly, facial abnormalities), however, cerebral aneurysms and other vascular abnormalities are frequent complications. MOPD II is a genetic disorder caused by mutations in the pericentrin (PCNT) gene (21q22). We report on a patient who came to our attention as a 22-year-old with subarachnoid bleeding due to a ruptured cranial aneurysm. Until then, the patient was thought and published to have Dubowitz syndrome; previously, he was treated with coronary bypass surgery for extensive coronary angiopathy. Consecutive genetic testing revealed MOPD II. After clinical stabilization, the patient was discharged to a specialized rehabilitation center where he died due to re-rupture of a cranial aneurysm. In patients with short stature-especially when clinical features are accompanied by vascular complications-MOPD II should be considered as a differential diagnosis leading to consecutive genetic testing. After detection of mutations in the PCNT gene, a full vascular status including cerebral imaging and cardiac evaluation needs to be determined in order to analyze vascular abnormalities and initiate prophylactic treatment.

  18. Profound microcephaly, primordial dwarfism with developmental brain malformations: a new syndrome.

    Science.gov (United States)

    Abdel-Salam, Ghada M H; Abdel-Hamid, Mohamed S; Saleem, Sahar N; Ahmed, Mahmoud K H; Issa, Mahmoud; Effat, Laila K; Kayed, Hisham F; Zaki, Maha S; Gaber, Khaled R

    2012-08-01

    We describe two sibs with a lethal form of profound congenital microcephaly, intrauterine and postnatal growth retardation, subtle skeletal changes, and poorly developed brain. The sibs had striking absent cranial vault with sloping of the forehead, large beaked nose, relatively large ears, and mandibular micro-retrognathia. Brain magnetic resonance imaging (MRI) revealed extremely simplified gyral pattern, large interhemispheric cyst and agenesis of corpus callosum, abnormally shaped hippocampus, and proportionately affected cerebellum and brainstem. In addition, fundus examination showed foveal hypoplasia with optic nerve atrophy. No abnormalities of the internal organs were found. This profound form of microcephaly was identified at 17 weeks gestation by ultrasound and fetal brain MRI helped in characterizing the developmental brain malformations in the second sib. Molecular analysis excluded mutations in potentially related genes such as RNU4ATAC, SLC25A19, and ASPM. These clinical and imaging findings are unlike that of any recognized severe forms of microcephaly which is believed to be a new microcephalic primordial dwarfism (MPD) with developmental brain malformations with most probably autosomal recessive inheritance based on consanguinity and similarly affected male and female sibs. Copyright © 2012 Wiley Periodicals, Inc.

  19. Smad6/Smurf1 overexpression in cartilage delays chondrocyte hypertrophy and causes dwarfism with osteopenia

    Science.gov (United States)

    Horiki, Mitsuru; Imamura, Takeshi; Okamoto, Mina; Hayashi, Makoto; Murai, Junko; Myoui, Akira; Ochi, Takahiro; Miyazono, Kohei; Yoshikawa, Hideki; Tsumaki, Noriyuki

    2004-01-01

    Biochemical experiments have shown that Smad6 and Smad ubiquitin regulatory factor 1 (Smurf1) block the signal transduction of bone morphogenetic proteins (BMPs). However, their in vivo functions are largely unknown. Here, we generated transgenic mice overexpressing Smad6 in chondrocytes. Smad6 transgenic mice showed postnatal dwarfism with osteopenia and inhibition of Smad1/5/8 phosphorylation in chondrocytes. Endochondral ossification during development in these mice was associated with almost normal chondrocyte proliferation, significantly delayed chondrocyte hypertrophy, and thin trabecular bone. The reduced population of hypertrophic chondrocytes after birth seemed to be related to impaired bone growth and formation. Organ culture of cartilage rudiments showed that chondrocyte hypertrophy induced by BMP2 was inhibited in cartilage prepared from Smad6 transgenic mice. We then generated transgenic mice overexpressing Smurf1 in chondrocytes. Abnormalities were undetectable in Smurf1 transgenic mice. Mating Smad6 and Smurf1 transgenic mice produced double-transgenic pups with more delayed endochondral ossification than Smad6 transgenic mice. These results provided evidence that Smurf1 supports Smad6 function in vivo. PMID:15123739

  20. Primordial dwarfism gene maintains Lin28 expression to safeguard embryonic stem cells from premature differentiation.

    Science.gov (United States)

    Dai, Qian; Luan, Guangxin; Deng, Li; Lei, Tingjun; Kang, Han; Song, Xu; Zhang, Yujun; Xiao, Zhi-Xiong; Li, Qintong

    2014-05-08

    Primordial dwarfism (PD) is characterized by global growth failure, both during embryogenesis and postnatally. Loss-of-function germline mutations in La ribonucleoprotein domain family, member 7 (LAPR7) have recently been linked to PD. Paradoxically, LARP7 deficiency was previously assumed to be associated with increased cell growth and proliferation via activation of positive transcription elongation factor b (P-TEFb). Here, we show that Larp7 deficiency likely does not significantly increase P-TEFb activity. We further discover that Larp7 knockdown does not affect pluripotency but instead primes embryonic stem cells (ESCs) for differentiation via downregulation of Lin28, a positive regulator of organismal growth. Mechanistically, we show that Larp7 interacts with a poly(A) polymerase Star-PAP to maintain Lin28 mRNA stability. We propose that proper regulation of Lin28 and PTEFb is essential for embryonic cells to achieve a sufficient number of cell divisions prior to differentiation and ultimately to maintain proper organismal size. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Dwarfism and feeding behaviours in Oligo–Miocene crocodiles from Riversleigh, northwestern Queensland, Australia

    Directory of Open Access Journals (Sweden)

    Michael Stein

    2016-02-01

    Full Text Available Instances of dwarfism in the fossil record are of interest to palaeontologists because they often provide insight into aspects of palaeoecology. Fossil species of Australian-Pacific mekosuchine genus Mekosuchus have been described as dwarf, primarily terrestrial crocodiles, in contrast with the nearly ubiquitous semi-aquatic habitus of extant crocodilians (Willis 1997. This hypothesis has been difficult to test because of limited knowledge of the cranial and postcranial skeleton of extinct taxa and the continuous nature of crocodilian growth. New crocodilian vertebral material from Riversleigh, northwestern Queensland, tentatively referred to Mekosuchus whitehunterensis Willis, 1997, displays morphological maturity indicative of adult snout-vent length little over a half-meter, proportionally smaller than extant dwarf taxa. Further, this material displays morphology that indicates a relatively large epaxial neck musculature for its body-size. These attributes suggest this dwarf mekosuchine employed unusual feeding behaviours. The ability to perform normal death-roll, de-fleshing behaviours would be limited in a mekosuchine of such small size. Given the powerful neck muscles and other anatomical features, it is more likely that this mekosuchine killed and/or dismembered its prey using a relatively forceful lifting and shaking of the head.

  2. Atlanto-axial malformation and instability in dogs with pituitary dwarfism due to an LHX3 mutation.

    Science.gov (United States)

    Voorbij, A M W Y; Meij, B P; van Bruggen, L W L; Grinwis, G C M; Stassen, Q E M; Kooistra, H S

    2015-01-01

    Canine pituitary dwarfism or combined pituitary hormone deficiency (CPHD) in shepherd dogs is associated with an LHX3 mutation and can lead to a wide range of clinical manifestations. Some dogs with CPHD have neurological signs that are localized to the cervical spine. In human CPHD, caused by an LHX3 mutation, anatomical abnormalities in the atlanto-axial (C1-C2) joint have been described. To evaluate the presence of atlanto-axial malformations in dogs with pituitary dwarfism associated with an LHX3 mutation and to investigate the degree of similarity between the atlanto-axial anomalies found in canine and human CPHD patients with an LHX3 mutation. Three client-owned Czechoslovakian wolfdogs and 1 client-owned German shepherd dog, previously diagnosed with pituitary dwarfism caused by an LHX3 mutation, with neurological signs indicating a cervical spinal disorder. Radiography, computed tomography, and magnetic resonance imaging of the cranial neck and skull, necropsy, and histology. Diagnostic imaging identified abnormal positioning of the dens axis and incomplete ossification of the suture lines between the ossification centers of the atlas with concurrent atlanto-axial instability and dynamic compression of the spinal cord by the dens axis. The malformations and aberrant motion at C1-C2 were confirmed at necropsy and histology. The atlanto-axial abnormalities of the dwarf dogs resemble those encountered in human CPHD patients with an LHX3 mutation. These findings suggest an association between the LHX3 mutation in dogs with CPHD and atlanto-axial malformations. Consequently, pituitary dwarfs should be monitored closely for neurological signs. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

  3. De Novo GMNN Mutations Cause Autosomal-Dominant Primordial Dwarfism Associated with Meier-Gorlin Syndrome.

    Science.gov (United States)

    Burrage, Lindsay C; Charng, Wu-Lin; Eldomery, Mohammad K; Willer, Jason R; Davis, Erica E; Lugtenberg, Dorien; Zhu, Wenmiao; Leduc, Magalie S; Akdemir, Zeynep C; Azamian, Mahshid; Zapata, Gladys; Hernandez, Patricia P; Schoots, Jeroen; de Munnik, Sonja A; Roepman, Ronald; Pearring, Jillian N; Jhangiani, Shalini; Katsanis, Nicholas; Vissers, Lisenka E L M; Brunner, Han G; Beaudet, Arthur L; Rosenfeld, Jill A; Muzny, Donna M; Gibbs, Richard A; Eng, Christine M; Xia, Fan; Lalani, Seema R; Lupski, James R; Bongers, Ernie M H F; Yang, Yaping

    2015-12-03

    Meier-Gorlin syndrome (MGS) is a genetically heterogeneous primordial dwarfism syndrome known to be caused by biallelic loss-of-function mutations in one of five genes encoding pre-replication complex proteins: ORC1, ORC4, ORC6, CDT1, and CDC6. Mutations in these genes cause disruption of the origin of DNA replication initiation. To date, only an autosomal-recessive inheritance pattern has been described in individuals with this disorder, with a molecular etiology established in about three-fourths of cases. Here, we report three subjects with MGS and de novo heterozygous mutations in the 5' end of GMNN, encoding the DNA replication inhibitor geminin. We identified two truncating mutations in exon 2 (the 1(st) coding exon), c.16A>T (p.Lys6(∗)) and c.35_38delTCAA (p.Ile12Lysfs(∗)4), and one missense mutation, c.50A>G (p.Lys17Arg), affecting the second-to-last nucleotide of exon 2 and possibly RNA splicing. Geminin is present during the S, G2, and M phases of the cell cycle and is degraded during the metaphase-anaphase transition by the anaphase-promoting complex (APC), which recognizes the destruction box sequence near the 5' end of the geminin protein. All three GMNN mutations identified alter sites 5' to residue Met28 of the protein, which is located within the destruction box. We present data supporting a gain-of-function mechanism, in which the GMNN mutations result in proteins lacking the destruction box and hence increased protein stability and prolonged inhibition of replication leading to autosomal-dominant MGS.

  4. Novel microcephalic primordial dwarfism disorder associated with variants in the centrosomal protein ninein.

    Science.gov (United States)

    Dauber, Andrew; Lafranchi, Stephen H; Maliga, Zoltan; Lui, Julian C; Moon, Jennifer E; McDeed, Cailin; Henke, Katrin; Zonana, Jonathan; Kingman, Garrett A; Pers, Tune H; Baron, Jeffrey; Rosenfeld, Ron G; Hirschhorn, Joel N; Harris, Matthew P; Hwa, Vivian

    2012-11-01

    Microcephalic primordial dwarfism (MPD) is a rare, severe form of human growth failure in which growth restriction is evident in utero and continues into postnatal life. Single causative gene defects have been identified in a number of patients with MPD, and all involve genes fundamental to cellular processes including centrosome functions. The objective of the study was to find the genetic etiology of a novel presentation of MPD. The design of the study was whole-exome sequencing performed on two affected sisters in a single family. Molecular and functional studies of a candidate gene were performed using patient-derived primary fibroblasts and a zebrafish morpholino oligonucleotides knockdown model. Two sisters presented with a novel subtype of MPD, including severe intellectual disabilities. NIN, encoding Ninein, a centrosomal protein critically involved in asymmetric cell division, was identified as a candidate gene, and functional impacts in fibroblasts and zebrafish were studied. From 34,606 genomic variants, two very rare missense variants in NIN were identified. Both probands were compound heterozygotes. In the zebrafish, ninein knockdown led to specific and novel defects in the specification and morphogenesis of the anterior neuroectoderm, resulting in a deformity of the developing cranium with a small, squared skull highly reminiscent of the human phenotype. We identified a novel clinical subtype of MPD in two sisters who have rare variants in NIN. We show, for the first time, that reduction of ninein function in the developing zebrafish leads to specific deficiencies of brain and skull development, offering a developmental basis for the myriad phenotypes in our patients.

  5. Majewski osteodysplastic primordial dwarfism type II (MOPD II): expanding the vascular phenotype.

    Science.gov (United States)

    Bober, Michael B; Khan, Nadia; Kaplan, Jennifer; Lewis, Kristi; Feinstein, Jeffrey A; Scott, Charles I; Steinberg, Gary K

    2010-04-01

    Majewski Osteodysplastic Primordial Dwarfism, Type II (MOPD II) is a rare, autosomal recessive disorder. Features include severe intrauterine growth retardation (IUGR), poor postnatal growth (adult stature approximately 100 cm), severe microcephaly, skeletal dysplasia, characteristic facial features, and normal or near normal intelligence. An Institutional Review Board (IRB) approved registry was created and currently follows 25 patients with a diagnosis of MOPD II. Based on previous studies, a neurovascular screening program was implemented and 13 (52%) of these patients have been found to have cerebral neurovascular abnormalities including moyamoya angiopathy and/or intracranial aneurysms. The typical moyamoya pathogenesis begins with vessel narrowing in the supraclinoid internal carotid artery, anterior cerebral (A1) or middle cerebral (M1) artery segments. The narrowing may predominate initially on one side, progresses to bilateral stenosis, with subsequent occlusion of the vessels and collateral formation. We present four patients who, on neurovascular screening, were found to have cerebrovascular changes. Two were asymptomatic, one presented with a severe headache and projectile vomiting related to a ruptured aneurysm, and one presented after an apparent decline in cognitive functioning. Analysis of the registry suggests screening for moyamoya disease be performed at the time of MOPD II diagnosis and at least every 12-18 months using MRA or computerized tomographic angiography (CTA). We believe this is imperative. If diagnosed early enough, re-vascularization and aneurysm treatment in skilled hands can be performed safely and prevent or minimize long-term sequelae in this population. Emergent evaluation is also needed when other neurologic or cardiac symptoms are present. (c) 2010 Wiley-Liss, Inc.

  6. Novel POC1A mutation in primordial dwarfism reveals new insights for centriole biogenesis.

    Science.gov (United States)

    Koparir, Asuman; Karatas, Omer F; Yuceturk, Betul; Yuksel, Bayram; Bayrak, Ali O; Gerdan, Omer F; Sagiroglu, Mahmut S; Gezdirici, Alper; Kirimtay, Koray; Selcuk, Ece; Karabay, Arzu; Creighton, Chad J; Yuksel, Adnan; Ozen, Mustafa

    2015-10-01

    POC1A encodes a WD repeat protein localizing to centrioles and spindle poles and is associated with short stature, onychodysplasia, facial dysmorphism and hypotrichosis (SOFT) syndrome. These main features are related to the defect in cell proliferation of chondrocytes in growth plate. In the current study, we aimed at identifying the molecular basis of two patients with primordial dwarfism (PD) in a single family through utilization of whole-exome sequencing. A novel homozygous p.T120A missense mutation was detected in POC1A in both patients, a known causative gene of SOFT syndrome, and confirmed using Sanger sequencing. To test the pathogenicity of the detected mutation, primary fibroblast cultures obtained from the patients and a control individual were used. For evaluating the global gene expression profile of cells carrying p.T120A mutation in POC1A, we performed the gene expression array and compared their expression profiles to those of control fibroblast cells. The gene expression array analysis showed that 4800 transcript probes were significantly deregulated in cells with p.T120A mutation in comparison to the control. GO term association results showed that deregulated genes are mostly involved in the extracellular matrix and cytoskeleton. Furthermore, the p.T120A missense mutation in POC1A caused the formation of abnormal mitotic spindle structure, including supernumerary centrosomes, and changes in POC1A were accompanied by alterations in another centrosome-associated WD repeat protein p80-katanin. As a result, we identified a novel mutation in POC1A of patients with PD and showed that this mutation causes the formation of multiple numbers of centrioles and multipolar spindles with abnormal chromosome arrangement. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Common mutations in the fibroblast growth factor receptor 3 (FGFR 3) gene account for achondroplasia, hypochondroplasia, and thanatophoric dwarfism

    Energy Technology Data Exchange (ETDEWEB)

    Bonaventure, J.; Rousseau, F.; Legeai-Mallet, L.; LeMerrer, M.; Munnich, A.; Maroteaux, P. [INSERM, Paris (France)

    1996-05-03

    The mapping of the achondroplasia locus to the short arm of chromosome 4 and the subsequent identification of a recurrent missense mutation (G380R) in the fibroblast growth factor receptor 3 (FGFR-3) gene has been followed by the detection of common FGFR-3 mutations in two clinically related disorders: thanatophoric dwarfism (types I and II) and hypochondroplasia. The relative clinical homogeneity of achondroplasia was substantiated by demonstration of its genetic homogeneity as more than 98% of all patients hitherto reported exhibit mutations in the transmembrane receptor domain. Although most hypochondroplasia cases were accounted for by a recurrent missense substitution (N540K) in the first tyrosine kinase (TK 1) domain of the receptor, a significant proportion (40%) of our patients did not harbor the N540K mutation and three hypochondroplasia families were not linked to the FGFR-3 locus, thus supporting clinical heterogeneity of this condition. In thanatophoric dwarfism (TD), a recurrent FGFR-3 mutation located in the second tyrosine kinase (TK 2) domain of the receptor was originally detected in 100% of TD II cases; in our series, seven distinct mutations in three different protein domains were identified in 25 of 26 TD I patients, suggesting that TD, like achondroplasia, is a genetically homogenous skeletal disorder. 31 refs., 4 figs., 2 tabs.

  8. Disruption of sonic hedgehog signaling in Ellis-van Creveld dwarfism confers protection against bipolar affective disorder.

    Science.gov (United States)

    Ginns, E I; Galdzicka, M; Elston, R C; Song, Y E; Paul, S M; Egeland, J A

    2015-10-01

    Ellis-van Creveld syndrome, an autosomal recessively inherited chondrodysplastic dwarfism, is frequent among Old Order Amish of Pennsylvania. Decades of longitudinal research on bipolar affective disorder (BPAD) revealed cosegregation of high numbers of EvC and Bipolar I (BPI) cases in several large Amish families descending from the same pioneer. Despite the high prevalence of both disorders in these families, no EvC individual has ever been reported with BPI. The proximity of the EVC gene to our previously reported chromosome 4p16 BPAD locus with protective alleles, coupled with detailed clinical observations that EvC and BPI do not occur in the same individuals, led us to hypothesize that the genetic defect causing EvC in the Amish confers protection from BPI. This hypothesis is supported by a significant negative association of these two disorders when contrasted with absence of disease (P=0.029, Fisher's exact test, two-sided, verified by permutation to estimate the null distribution of the test statistic). As homozygous Amish EVC mutations causing EvC dwarfism do so by disrupting sonic hedgehog (Shh) signaling, our data implicate Shh signaling in the underlying pathophysiology of BPAD. Understanding how disrupted Shh signaling protects against BPI could uncover variants in the Shh pathway that cause or increase risk for this and related mood disorders.

  9. Novel splice site mutation in the growth hormone receptor gene in Turkish patients with Laron-type dwarfism.

    Science.gov (United States)

    Arman, Ahmet; Ozon, Alev; Isguven, Pinar S; Coker, Ajda; Peker, Ismail; Yordam, Nursen

    2008-01-01

    Growth hormone (GH) is involved in growth, and fat and carbohydrate metabolism. Interaction of GH with the GH receptor (GHR) is necessary for systemic and local production of insulin-like growth factor-I (IGF-I) which mediates GH actions. Mutations in the GHR cause severe postnatal growth failure; the disorder is an autosomal recessive genetic disease resulting in GH insensitivity, called Laron syndrome. It is characterized by dwarfism with elevated serum GH and low levels of IGF-I. We analyzed the GHR gene for mutations and polymorphisms in eight patients with Laron-type dwarfism from six families. We found three missense mutations (S40L, V125A, I526L), one nonsense mutation (W157X), and one splice site mutation in the extracellular domain of GHR. Furthermore, G168G and exon 3 deletion polymorphisms were detected in patients with Laron syndrome. The splice site mutation, which is a novel mutation, was located at the donor splice site of exon 2/ intron 2 within GHR. Although this mutation changed the highly conserved donor splice site consensus sequence GT to GGT by insertion of a G residue, the intron splicing between exon 2 and exon 3 was detected in the patient. These results imply that the splicing occurs arthe GT site in intron 2, leaving the extra inserted G residue at the end of exon 2, thus changing the open reading frame of GHR resulting in a premature termination codon in exon 3.

  10. Catalytically Active Guanylyl Cyclase B Requires Endoplasmic Reticulum-mediated Glycosylation, and Mutations That Inhibit This Process Cause Dwarfism.

    Science.gov (United States)

    Dickey, Deborah M; Edmund, Aaron B; Otto, Neil M; Chaffee, Thomas S; Robinson, Jerid W; Potter, Lincoln R

    2016-05-20

    C-type natriuretic peptide activation of guanylyl cyclase B (GC-B), also known as natriuretic peptide receptor B or NPR2, stimulates long bone growth, and missense mutations in GC-B cause dwarfism. Four such mutants (L658F, Y708C, R776W, and G959A) bound (125)I-C-type natriuretic peptide on the surface of cells but failed to synthesize cGMP in membrane GC assays. Immunofluorescence microscopy also indicated that the mutant receptors were on the cell surface. All mutant proteins were dephosphorylated and incompletely glycosylated, but dephosphorylation did not explain the inactivation because the mutations inactivated a "constitutively phosphorylated" enzyme. Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. We conclude that endoplasmic reticulum-mediated glycosylation is required for the formation of an active catalytic, but not ligand-binding domain, and that mutations that inhibit this process cause dwarfism.

  11. MORPHO‐FUNCTIONAL RE‐ESTABLISHMENT OF CRANIO‐FACIAL GROWTH DISORDERS IN PITUITARY DWARFISM BY RHGH THERAPY

    Directory of Open Access Journals (Sweden)

    Adriana BĂLAN

    2013-06-01

    Full Text Available The present study evaluates the cranio‐facial growth disorders in a series of patients suffering from pituitary dwarfism, as a result of the therapy with recombinant human growth hormone (rhGH. Included in the study were 15 children diagnosed with pituitary dwarfism in the Endocrinology Clinics of the ”Sf. Spiridon” Hospital of Iasi, subjected to a treatment with rhGH for 2 years. After the application of the therapy, the parameters of general physical development were followed and the dental ortho‐ pantomography and profile cephalometry were analyzed. The results obtained confirm a general physical growth of about 1.3 cm/month in the first year of treatment, followed by values around 1.1 cm/month in the second year. Cranio‐facial development was improved by the increase of both mandibular vertical branch and facial height. At the level of the dental arches, one could observe improved sagital and transversal relations at molar level, as well as a regulating tendency of dental eruption. The therapy with rhGH is thus influent at cranio‐facial level, favourizing the development of maxillaries, regulation of dental eruption and the aesthetic aspects.

  12. Screening for cerebrovascular disease in microcephalic osteodysplastic primordial dwarfism type II (MOPD II): an evidence-based proposal.

    Science.gov (United States)

    Perry, Luke D; Robertson, Fergus; Ganesan, Vijeya

    2013-04-01

    Microcephalic osteodysplastic primordial dwarfism type II (OMIM 210720) is a rare autosomal recessive condition frequently associated with early-onset cerebrovascular disease. Presymptomatic detection and intervention could prevent the adverse consequences associated with this. We reviewed published cases of microcephalic osteodysplastic primordial dwarfism type II to ascertain prevalence and characteristics of cerebrovascular disease and use these data to propose an evidence-based approach to cerebrovascular screening. Of 147 cases identified, 47 had cerebrovascular disease (32%), including occlusive arteriopathy (including moyamoya) and cerebral aneurysmal disease. Occlusive disease occurred in younger individuals, and progression can be both rapid and clinically silent. A reasonable screening approach would be magnetic resonance imaging and angiography of the cervical and intracranial circulation at diagnosis, repeated at yearly intervals until 10 years, and every 2 years thereafter, unless clinical concerns occur earlier. At present it would appear that this needs to be life-long. Families and professionals should be alerted to the potential significance of neurologic symptoms and measures should be taken to maintain good vascular health in affected individuals. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Phenotypic characterization of the Komeda miniature rat Ishikawa, an animal model of dwarfism caused by a mutation in Prkg2.

    Science.gov (United States)

    Tsuchida, Atsuko; Yokoi, Norihide; Namae, Misako; Fuse, Masanori; Masuyama, Taku; Sasaki, Masashi; Kawazu, Shoji; Komeda, Kajuro

    2008-12-01

    The Komeda miniature rat Ishikawa (KMI) is a spontaneous animal model of dwarfism caused by a mutation in Prkg2, which encodes cGMP-dependent protein kinase type II (cGKII). This strain has been maintained as a segregating inbred strain for the mutated allele mri. In this study, we characterized the phenotype of the KMI strain, particularly growth traits, craniofacial measurements, and organ weights. The homozygous mutant (mri/mri) animals were approximately 70% to 80% of the size of normal, heterozygous (mri/+) animals in regard to body length, weight, and naso-occipital length of the calvarium, and the retroperitoneal fat of mri/mri rats was reduced greatly. In addition, among progeny of the (BNxKMI-mri/mri)F1xKMI-mri/mri backcross, animals with the KMI phenotype (mri/mri) were easily distinguished from those showing the wild-type phenotype (mri/+) by using growth traits such as body length and weight. Genetic analysis revealed that all of the backcrossed progeny exhibiting the KMI phenotype were homozygous for the KMI allele in the 1.2-cM region between D14Rat5 and D14Rat80 on chromosome 14, suggesting strongly that mri acts in a completely recessive manner. The KMI strain is the first and only rat model with a confirmed mutation in Prkg2 and is a valuable model for studying dwarfism and longitudinal growth traits in humans and for functional studies of cGKII.

  14. Dwarfism in Mice Lacking Collagen-binding Integrins α2β1 and α11β1 Is Caused by Severely Diminished IGF-1 Levels*

    Science.gov (United States)

    Blumbach, Katrin; Niehoff, Anja; Belgardt, Bengt F.; Ehlen, Harald W. A.; Schmitz, Markus; Hallinger, Ralf; Schulz, Jan-Niklas; Brüning, Jens C.; Krieg, Thomas; Schubert, Markus; Gullberg, Donald; Eckes, Beate

    2012-01-01

    Mice with a combined deficiency in the α2β1 and α11β1 integrins lack the major receptors for collagen I. These mutants are born with inconspicuous differences in size but develop dwarfism within the first 4 weeks of life. Dwarfism correlates with shorter, less mineralized and functionally weaker bones that do not result from growth plate abnormalities or osteoblast dysfunction. Besides skeletal dwarfism, internal organs are correspondingly smaller, indicating proportional dwarfism and suggesting a systemic cause for the overall size reduction. In accordance with a critical role of insulin-like growth factor (IGF)-1 in growth control and bone mineralization, circulating IGF-1 levels in the sera of mice lacking either α2β1 or α11β1 or both integrins were sharply reduced by 39%, 64%, or 81% of normal levels, respectively. Low hepatic IGF-1 production resulted from diminished growth hormone-releasing hormone expression in the hypothalamus and, subsequently, reduced growth hormone expression in the pituitary glands of these mice. These findings point out a novel role of collagen-binding integrin receptors in the control of growth hormone/IGF-1-dependent biological activities. Thus, coupling hormone secretion to extracellular matrix signaling via integrins represents a novel concept in the control of endocrine homeostasis. PMID:22210772

  15. The Agrobacterium rhizogenes oncogenes rolB and ORF13 increase formation of generative shoots and induce dwarfism in Arabidopsis thaliana (L.) Heynh

    DEFF Research Database (Denmark)

    Kodahl, Nete; Müller, Renate; Lütken, Henrik Vlk

    2016-01-01

    B oncogene yield plants with increased formation of generative shoots, but also result in some degree of premature senescence of vegetative organs. The extreme dwarfism seen in ORF13-lines indicate that this oncogene may be more important in the dwarfing response of plants transformed with the wild type Ri...

  16. Mutation in WDR4 impairs tRNA m(7)G46 methylation and causes a distinct form of microcephalic primordial dwarfism.

    Science.gov (United States)

    Shaheen, Ranad; Abdel-Salam, Ghada M H; Guy, Michael P; Alomar, Rana; Abdel-Hamid, Mohamed S; Afifi, Hanan H; Ismail, Samira I; Emam, Bayoumi A; Phizicky, Eric M; Alkuraya, Fowzan S

    2015-09-28

    Primordial dwarfism is a state of extreme prenatal and postnatal growth deficiency, and is characterized by marked clinical and genetic heterogeneity. Two presumably unrelated consanguineous families presented with an apparently novel form of primordial dwarfism in which severe growth deficiency is accompanied by distinct facial dysmorphism, brain malformation (microcephaly, agenesis of corpus callosum, and simplified gyration), and severe encephalopathy with seizures. Combined autozygome/exome analysis revealed a novel missense mutation in WDR4 as the likely causal variant. WDR4 is the human ortholog of the yeast Trm82, an essential component of the Trm8/Trm82 holoenzyme that effects a highly conserved and specific (m(7)G46) methylation of tRNA. The human mutation and the corresponding yeast mutation result in a significant reduction of m(7)G46 methylation of specific tRNA species, which provides a potential mechanism for primordial dwarfism associated with this lesion, since reduced m(7)G46 modification causes a growth deficiency phenotype in yeast. Our study expands the number of biological pathways underlying primordial dwarfism and adds to a growing list of human diseases linked to abnormal tRNA modification.

  17. Dwarfism in mice lacking collagen-binding integrins α2β1 and α11β1 is caused by severely diminished IGF-1 levels.

    Science.gov (United States)

    Blumbach, Katrin; Niehoff, Anja; Belgardt, Bengt F; Ehlen, Harald W A; Schmitz, Markus; Hallinger, Ralf; Schulz, Jan-Niklas; Brüning, Jens C; Krieg, Thomas; Schubert, Markus; Gullberg, Donald; Eckes, Beate

    2012-02-24

    Mice with a combined deficiency in the α2β1 and α11β1 integrins lack the major receptors for collagen I. These mutants are born with inconspicuous differences in size but develop dwarfism within the first 4 weeks of life. Dwarfism correlates with shorter, less mineralized and functionally weaker bones that do not result from growth plate abnormalities or osteoblast dysfunction. Besides skeletal dwarfism, internal organs are correspondingly smaller, indicating proportional dwarfism and suggesting a systemic cause for the overall size reduction. In accordance with a critical role of insulin-like growth factor (IGF)-1 in growth control and bone mineralization, circulating IGF-1 levels in the sera of mice lacking either α2β1 or α11β1 or both integrins were sharply reduced by 39%, 64%, or 81% of normal levels, respectively. Low hepatic IGF-1 production resulted from diminished growth hormone-releasing hormone expression in the hypothalamus and, subsequently, reduced growth hormone expression in the pituitary glands of these mice. These findings point out a novel role of collagen-binding integrin receptors in the control of growth hormone/IGF-1-dependent biological activities. Thus, coupling hormone secretion to extracellular matrix signaling via integrins represents a novel concept in the control of endocrine homeostasis.

  18. Biochemical and hormonal changes induced by one week of administration of rIGF-I to patients with Laron type dwarfism

    DEFF Research Database (Denmark)

    Laron, Z; Klinger, B; Jensen, L T

    1991-01-01

    OBJECTIVE: The purpose of this investigation was to evaluate the effectiveness of short-term administration of recombinant biosynthetic IGF-I on patients with an hereditary inability to generate this hormone. DESIGN AND PATIENTS: Ten patients with Laron type dwarfism (LTD) (4 males, six females) ...

  19. Surgical outcomes of Majewski osteodysplastic primordial dwarfism Type II with intracranial vascular anomalies.

    Science.gov (United States)

    Teo, Mario; Johnson, Jeremiah N; Bell-Stephens, Teresa E; Marks, Michael P; Do, Huy M; Dodd, Robert L; Bober, Michael B; Steinberg, Gary K

    2016-12-01

    OBJECTIVE Majewski osteodysplastic primordial dwarfism Type II (MOPD II) is a rare genetic disorder. Features of it include extremely small stature, severe microcephaly, and normal or near-normal intelligence. Previous studies have found that more than 50% of patients with MOPD II have intracranial vascular anomalies, but few successful surgical revascularization or aneurysm-clipping cases have been reported because of the diminutive arteries and narrow surgical corridors in these patients. Here, the authors report on a large series of patients with MOPD II who underwent surgery for an intracranial vascular anomaly. METHODS In conjunction with an approved prospective registry of patients with MOPD II, a prospectively collected institutional surgical database of children with MOPD II and intracranial vascular anomalies who underwent surgery was analyzed retrospectively to establish long-term outcomes. RESULTS Ten patients with MOPD II underwent surgery between 2005 and 2012; 5 patients had moyamoya disease (MMD), 2 had intracranial aneurysms, and 3 had both MMD and aneurysms. Patients presented with transient ischemic attack (TIA) (n = 2), ischemic stroke (n = 2), intraparenchymal hemorrhage from MMD (n = 1), and aneurysmal subarachnoid hemorrhage (n = 1), and 4 were diagnosed on screening. The mean age of the 8 patients with MMD, all of whom underwent extracranial-intracranial revascularization (14 indirect, 1 direct) was 9 years (range 1-17 years). The mean age of the 5 patients with aneurysms was 15.5 years (range 9-18 years). Two patients experienced postoperative complications (1 transient weakness after clipping, 1 femoral thrombosis that required surgical repair). During a mean follow-up of 5.9 years (range 3-10 years), 3 patients died (1 of subarachnoid hemorrhage, 1 of myocardial infarct, and 1 of respiratory failure), and 1 patient had continued TIAs. All of the surviving patients recovered to their neurological baseline. CONCLUSIONS Patients with MMD

  20. The heterozygous disproportionate micromelia (dmm) mouse: morphological changes in fetal cartilage precede postnatal dwarfism and compared with lethal homozygotes can explain the mild phenotype.

    Science.gov (United States)

    Seegmiller, Robert E; Bomsta, Brandon D; Bridgewater, Laura C; Niederhauser, Cindy M; Montaño, Carolina; Sudweeks, Sterling; Eyre, David R; Fernandes, Russell J

    2008-11-01

    The disproportionate micromelia (Dmm) mouse has a mutation in the C-propeptide coding region of the Col2a1 gene that causes lethal dwarfism when homozygous (Dmm/Dmm) but causes only mild dwarfism observable approximately 1-week postpartum when heterozygous (Dmm/+). The purpose of this study was 2-fold: first, to analyze and quantify morphological changes that precede the expression of mild dwarfism in Dmm/+ animals, and second, to compare morphological alterations between Dmm/+ and Dmm/Dmm fetal cartilage that may correlate with the marked skeletal differences between mild and lethal dwarfism. Light and electron transmission microscopy were used to visualize structure of chondrocytes and extracellular matrix (ECM) of fetal rib cartilage. Both Dmm/+ and Dmm/Dmm fetal rib cartilage had significantly larger chondrocytes, greater cell density, and less ECM per unit area than +/+ littermates. Quantitative RT-PCR showed a decrease in aggrecan mRNA in Dmm/+ vs +/+ cartilage. Furthermore, the cytoplasm of chondrocytes in Dmm/+ and Dmm/Dmm cartilage was occupied by significantly more distended rough endoplasmic reticulum (RER) compared with wild-type chondrocytes. Fibril diameters and packing densities of +/+ and Dmm/+ cartilage were similar, but Dmm/Dmm cartilage showed thinner, sparsely distributed fibrils. These findings support the prevailing hypothesis that a C-propeptide mutation could interrupt the normal assembly and secretion of Type II procollagen trimers, resulting in a buildup of proalpha1(II) chains in the RER and a reduced rate of matrix synthesis. Thus, intracellular entrapment of proalpha1(II) seems to be primarily responsible for the dominant-negative effect of the Dmm mutation in the expression of dwarfism.

  1. Dwarfism with joint laxity in Friesian horses is associated with a splice site mutation in B4GALT7.

    Science.gov (United States)

    Leegwater, Peter A; Vos-Loohuis, Manon; Ducro, Bart J; Boegheim, Iris J; van Steenbeek, Frank G; Nijman, Isaac J; Monroe, Glen R; Bastiaansen, John W M; Dibbits, Bert W; van de Goor, Leanne H; Hellinga, Ids; Back, Willem; Schurink, Anouk

    2016-10-28

    Inbreeding and population bottlenecks in the ancestry of Friesian horses has led to health issues such as dwarfism. The limbs of dwarfs are short and the ribs are protruding inwards at the costochondral junction, while the head and back appear normal. A striking feature of the condition is the flexor tendon laxity that leads to hyperextension of the fetlock joints. The growth plates of dwarfs display disorganized and thickened chondrocyte columns. The aim of this study was to identify the gene defect that causes the recessively inherited trait in Friesian horses to understand the disease process at the molecular level. We have localized the genetic cause of the dwarfism phenotype by a genome wide approach to a 3 Mb region on the p-arm of equine chromosome 14. The DNA of two dwarfs and one control Friesian horse was sequenced completely and we identified the missense mutation ECA14:g.4535550C > T that cosegregated with the phenotype in all Friesians analyzed. The mutation leads to the amino acid substitution p.(Arg17Lys) of xylosylprotein beta 1,4-galactosyltransferase 7 encoded by B4GALT7. The protein is one of the enzymes that synthesize the tetrasaccharide linker between protein and glycosaminoglycan moieties of proteoglycans of the extracellular matrix. The mutation not only affects a conserved arginine codon but also the last nucleotide of the first exon of the gene and we show that it impedes splicing of the primary transcript in cultured fibroblasts from a heterozygous horse. As a result, the level of B4GALT7 mRNA in fibroblasts from a dwarf is only 2 % compared to normal levels. Mutations in B4GALT7 in humans are associated with Ehlers-Danlos syndrome progeroid type 1 and Larsen of Reunion Island syndrome. Growth retardation and ligamentous laxity are common manifestations of these syndromes. We suggest that the identified mutation of equine B4GALT7 leads to the typical dwarfism phenotype in Friesian horses due to deficient splicing of transcripts of

  2. Majewski osteodysplastic primordial dwarfism type II (MOPD II) syndrome previously diagnosed as Seckel syndrome: report of a novel mutation of the PCNT gene.

    Science.gov (United States)

    Piane, Maria; Della Monica, Matteo; Piatelli, Gianluca; Lulli, Patrizia; Lonardo, Fortunato; Chessa, Luciana; Scarano, Gioacchino

    2009-11-01

    We report on a 3-year-old boy with prenatal onset of proportionate dwarfism, postnatal severe microcephaly, high forehead with receded hairline, sparse scalp hair, beaked nose, mild retrognathia and hypotonia diagnosed at birth as Seckel syndrome. At age 3 years, he became paralyzed due to a cerebrovascular malformation. Based on the clinical and radiological features showing evidence of skeletal dysplasia, the diagnosis was revised to Majewski osteodysplastic primordial dwarfism type II (MOPD II) syndrome. Western blot analysis of the patient's lymphoblastoid cell line lysate showed the absence of the protein pericentrin. Subsequent molecular analysis identified a novel homozygous single base insertion (c.1527_1528insA) in exon 10 of the PCNT gene, which leads to a frameshift (Treo510fs) and to premature protein truncation. PCNT mutations must be considered diagnostic of MOPD II syndrome. A possible role of pericentrin in the development of cerebral vessels is suggested. Copyright 2009 Wiley-Liss, Inc.

  3. A new mutation of the PCNT gene in a Colombian patient with microcephalic osteodysplastic primordial dwarfism type II: a case report.

    Science.gov (United States)

    Pachajoa, Harry; Ruiz-Botero, Felipe; Isaza, Carolina

    2014-06-13

    Microcephalic osteodysplastic primordial dwarfism is a syndrome characterized by the presence of intrauterine growth restriction, post-natal growth deficiency and microcephaly. Microcephalic osteodysplastic primordial dwarfism type II is the most distinctive syndrome in this group of entities. Individuals affected by this disease present at an adult height of less than 100 cm, a post-pubertal head circumference of 40 cm or less, mild mental retardation, an outgoing personality and bone dysplasia. We report the first case of a five-year-old Colombian boy of mixed race ancestry (mestizo), with clinical features of microcephaly, prominent and narrow nose, arched palate, amelogenesis imperfecta, short stature, tall and narrow pelvis, disproportionate shortening of fore-arms and legs, and mild coxa vara. Analysis of the PCNT gene by sequencing showed the presence of a nucleotide change in exon 10, c. 1468C>T, evidencing a new mutation not reported in the literature for microcephalic osteodysplastic primordial dwarfism. The new mutation identified in this case could be associated with the severity of the phenotypic expression of the disease, resulting in the extreme short stature of the patient. Further studies are required to reach an explanation that can justify such findings, and it is vital to emphasize the importance of detection and follow-up by the epidemiological surveillance groups in birth defects and rare diseases.

  4. Mutations in ORC1, encoding the largest subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome.

    Science.gov (United States)

    Bicknell, Louise S; Walker, Sarah; Klingseisen, Anna; Stiff, Tom; Leitch, Andrea; Kerzendorfer, Claudia; Martin, Carol-Anne; Yeyati, Patricia; Al Sanna, Nouriya; Bober, Michael; Johnson, Diana; Wise, Carol; Jackson, Andrew P; O'Driscoll, Mark; Jeggo, Penny A

    2011-02-27

    Studies into disorders of extreme growth failure (for example, Seckel syndrome and Majewski osteodysplastic primordial dwarfism type II) have implicated fundamental cellular processes of DNA damage response signaling and centrosome function in the regulation of human growth. Here we report that mutations in ORC1, encoding a subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome. We establish that these mutations disrupt known ORC1 functions including pre-replicative complex formation and origin activation. ORC1 deficiency perturbs S-phase entry and S-phase progression. Additionally, we show that Orc1 depletion in zebrafish is sufficient to markedly reduce body size during rapid embryonic growth. Our data suggest a model in which ORC1 mutations impair replication licensing, slowing cell cycle progression and consequently impeding growth during development, particularly at times of rapid proliferation. These findings establish a novel mechanism for the pathogenesis of microcephalic dwarfism and show a surprising but important developmental impact of impaired origin licensing.

  5. Genomic and pathogenic analysis of a Muscovy duck parvovirus strain causing short beak and dwarfism syndrome without tongue protrusion.

    Science.gov (United States)

    Fu, Qiuling; Huang, Yu; Wan, Chunhe; Fu, Guanghua; Qi, Baomin; Cheng, Longfei; Shi, Shaohua; Chen, Hongmei; Liu, Rongchang; Chen, Zhenhai

    2017-07-12

    In 2008, clinical cases of short beak and dwarfism syndrome (SBDS) caused by Muscovy duck parvovirus (MDPV) infection were found in mule duck and Taiwan white duck farms in Fujian, China. A MDPV LH strain causing duck SBDS without tongue protrusion was isolated in this study. Phylogenetic analysis show that the MDPV LH strain was clustered together with other MDPV strains, but divergent from GPV isolates. Two major fragment deletions were found in the inverted terminal repeats (ITR) of MDPV LH similar to the ones in the ITR of MDPV GX5, YY and SAAS-SHNH strains. To investigate the pathogenicity of the MDPV LH strain, virus infection of young mule ducks was performed. The infected ducks showed SBDS symptoms including retard growth and shorten beaks without tongue protrusion. Atrophy of thymus, spleen and bursa of Fabricius was identified in the infected ducks. The results show that MDPV LH strain is moderately pathogenic to mule duck, leading to occurrence of SBDS. As far as we know, it is the first study showing that SBDS without tongue protrusion, and atrophy of thymus, spleen and bursa of Fabricius possibly associated with immunosuppression were found in the MDPV-infected ducks. The established duck-MDPV-SBDS system will help us to further work on the virus pathogenesis and develop efficacious vaccine against MDPV infection. Copyright © 2017. Published by Elsevier Ltd.

  6. Mutation in PLK4, encoding a master regulator of centriole formation, defines a novel locus for primordial dwarfism.

    Science.gov (United States)

    Shaheen, Ranad; Al Tala, Saeed; Almoisheer, Agaadir; Alkuraya, Fowzan S

    2014-12-01

    Primordial dwarfism (PD) is a heterogeneous clinical entity characterised by severe prenatal and postnatal growth deficiency. Despite the recent wave of disease gene discovery, the causal mutations in many PD patients remain unknown. To describe a PD family that maps to a novel locus. Clinical, imaging and laboratory phenotyping of a new family with PD followed by autozygosity mapping, linkage analysis and candidate gene sequencing. We describe a multiplex consanguineous Saudi family in which two full siblings and one half-sibling presented with classical features of Seckel syndrome in addition to optic nerve hypoplasia. We were able to map the phenotype to a single novel locus on 4q25-q28.2, in which we identified a five base-pair deletion in PLK4, which encodes a master regulator of centriole duplication. Our discovery further confirms the role of genes involved in centriole biology in the pathogenesis of PD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  7. Further delineation of the clinical spectrum in RNU4ATAC related microcephalic osteodysplastic primordial dwarfism type I.

    Science.gov (United States)

    Abdel-Salam, Ghada M H; Abdel-Hamid, Mohamed S; Hassan, Nihal A; Issa, Mahmoud Y; Effat, Laila; Ismail, Samira; Aglan, Mona S; Zaki, Maha S

    2013-08-01

    We describe five patients from three different families with microcephalic osteodysplastic primordial dwarfism type I (MOPD I), which was molecularly confirmed by homozygosity for the g.51G >A and g.55G >A mutations in RNU4ATAC, respectively. The patients showed the classical phenotype and demonstrated in addition variable degrees of gyration abnormalities and malformations of the callosal body with an interhemispheric cyst. One patient also showed underdevelopment of the cerebellar vermis. This confirms that cortical malformations should be considered cardinal manifestations of MOPD I. Oculocutaneous albinism, brain hemorrhage and chilblains have been found to be associated with MOPD I. The present study showed lack of retinal pigmentation in three patients of whom two had an unusually fair complexion of hair and skin. One patient was found to have a hematoma in the left thalamus. This may indicate that both pigmentary abnormalities and vascular anomalies may be part of the phenotype of MOPD I as well. Copyright © 2013 Wiley Periodicals, Inc.

  8. Mice Deficient in NF-κB p50 and p52 or RANK Have Defective Growth Plate Formation and Post-natal Dwarfism

    Institute of Scientific and Technical Information of China (English)

    Lianping Xing; Di Chen; Brendan F.Boyce

    2013-01-01

    NF-κBp50/p52 double knockout (dKO) and RANK KO mice have no osteoclasts and develop severe osteopetrosis associated with dwarfism. In contrast, Op/Op mice, which form few osteoclasts, and Src KO mice, which have osteoclasts with defective resorptive function, are osteopetrotic, but they are not dwarfed. Here, we compared the morphologic features of long bones from p50/p52 dKO, RANK KO, Op/Op and Src KO mice to attempt to explain the differences in their long bone lengths. We found that growth plates in p50/p52 dKO and RANK KO mice are significantly thicker than those in WT mice due to a 2-3-fold increase in the hypertrophic chondrocyte zone associated with normal a proliferative chondrocyte zone. This growth plate abnormality disappears when animals become older, but their dwarfism persists. Op/Op or Src KO mice have relatively normal growth plate morphology. In-situ hybridization study of long bones from p50/p52 dKO mice showed marked thickening of the growth plate region containing type 10 collagen-expressing chondrocytes. Treatment of micro-mass chondrocyte cultures with RANKL did not affect expression levels of type 2 collagen and Sox9, markers for proliferative chondrocytes, but RANKL reduced the number of type 10 collagen-expressing hypertrophic chondrocytes. Thus, RANK/NF-κB signaling plays a regulatory role in post-natal endochondral ossification that maintains hypertrophic conversion and prevents dwarfism in normal mice.

  9. Short beak and dwarfism syndrome of mule duck is caused by a distinct lineage of goose parvovirus.

    Science.gov (United States)

    Palya, Vilmos; Zolnai, Anna; Benyeda, Zsófia; Kovács, Edit; Kardi, Veronika; Mató, Tamás

    2009-04-01

    From the early 1970s to the present, numerous cases of short beak and dwarfism syndrome (SBDS) have been reported in mule ducks from France. The animals showed strong growth retardation with smaller beak and tarsus. It was suggested that the syndrome was caused by goose parvovirus on the basis of serological investigation, but the causative agent has not been isolated and the disease has not so far been reproduced by experimental infection. The aim of the present study was to characterize the virus strains isolated from field cases of SBDS, and to reproduce the disease experimentally. Phylogenetic analysis proved that the parvovirus isolates obtained from SBDS of mule duck belonged to a distinct lineage of goose parvovirus-related group of waterfowl parvoviruses. The authors carried out experimental infections of 1-day-old, 2-week-old and 3-week-old mule ducks by the oral route with three different parvovirus strains: strain D17/99 of goose parvovirus from Derzsy's disease, strain FM of Muscovy duck parvovirus from the parvovirus disease of Muscovy ducks, and strain D176/02 isolated from SBDS of mule duck. The symptoms of SBDS of the mule duck could only be reproduced with the mule duck isolate (strain D176/02) following 1-day-old inoculation. Infection with a genetically different strain of goose parvovirus isolated from classical Derzsy's disease (D17/99) or with the Muscovy duck parvovirus strain (FM) did not cause any clinical symptoms or pathological lesions in mule ducks.

  10. Embryonic death, dwarfism and fetal malformations after irradiation of embryos at the zygote stage. Studies on two mouse strains

    Energy Technology Data Exchange (ETDEWEB)

    Jacquet, P.; Saint-Georges, L. de; Baugnet-Mahieu, L. [Laboratory of Radiobiology, Department of Radioprotection, CEN/SCK, Mol (Belgium); Vankerkom, J. [Division of Environmental Research, VITO, Mol (Belgium)

    1995-11-01

    Female mice of the BALB/c and CF1 strains were mated and irradiated with various doses of X-rays 7 h after presumed fertilization. 18 days later, females were killed and their uteri examined for prenatal mortality at the different stages of development. Living fetuses were weighed and examined for the presence of external malformations. A number of them were also examined for skeletal anomalies. Radiation induced mainly a dose-dependent increase of the preimplantation loss in the BALB/c strain and of the early postimplantation loss in the CF1 strain. Embryos of the BALB/c strain were refractory to the induction of teratogenic effects after such preimplantation irradiation. In CF1 mice, the frequency of malformed fetuses increased regularly after irradiation, the difference with controls being significant for the doses of 10, 50 and 100 cGy. Dwarfism occurrence also appeared to be increased by irradiation in this strain, although the importance of this effect varied depending on the criterion chosen for the assessment of dwarfs. With the definition proposed in the present paper, the increase in the frequency of dwarfs paralleled that of malformed fetuses, being significant after doses of 50 and 100 cGy. Irradiation did not increase the frequency of skeletal anomalies. A careful examination of the various data obtained to date led us to conclude that radiation may possibly be teratogenic in several mouse strains, when administered as early as during the one-cell stage and, to a lesser extent, during the following preimplantation stages. However, early prenatal mortality will remain by far the greatest risk associated with an exposure to radiation during this period. Moreover, the relativity of the risk of abnormality due to such irradiation should be considered in the context of the high prevalence of developmental defects spontaneously occurring during human pregnancy.

  11. Identification of Goose-Origin Parvovirus as a Cause of Newly Emerging Beak Atrophy and Dwarfism Syndrome in Ducklings.

    Science.gov (United States)

    Yu, Kexiang; Ma, Xiuli; Sheng, Zizhang; Qi, Lihong; Liu, Cunxia; Wang, Dan; Huang, Bing; Li, Feng; Song, Minxun

    2016-08-01

    A recent epizootic outbreak, in China, of duck beak atrophy and dwarfism syndrome (BADS) was investigated using electron microscopic, genetic, and virological studies, which identified a parvovirus with a greater similarity to goose parvovirus (GPV) (97% protein homology) than to Muscovy duck parvovirus (MDPV) (90% protein homology). The new virus, provisionally designated GPV-QH15, was found to be antigenically more closely related to GPV than to MDPV in a virus neutralization assay. These findings were further supported by phylogenetic analysis showing that GPV-QH15 evolved from goose lineage parvoviruses, rather than from Muscovy duck- or other duck species-related parvoviruses. In all, two genetic lineages (GPV I and GPV II) were identified from the GPV samples analyzed, and GPV-QH15 was found to be closely clustered with two known goose-origin parvoviruses (GPVa2006 and GPV1995), together forming a distinctive GPV IIa sublineage. Finally, structural modeling revealed that GPV-QH15 and the closely related viruses GPVa2006 and GPV1995 possessed identical clusters of receptor-interacting amino acid residues in the VP2 protein, a major determinant of viral receptor binding and host specificity. Significantly, these three viruses differed from MDPVs and other GPVs at these positions. Taken together, these results suggest that GPV-QH15 represents a new variant of goose-origin parvovirus that currently circulates in ducklings and causes BADS, a syndrome reported previously in Europe. This new finding highlights the need for future surveillance of GPV-QH15 in poultry in order to gain a better understanding of both the evolution and the biology of this emerging parvovirus. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  12. A contracted DNA repeat in LHX3 intron 5 is associated with aberrant splicing and pituitary dwarfism in German shepherd dogs.

    Directory of Open Access Journals (Sweden)

    Annemarie M W Y Voorbij

    Full Text Available Dwarfism in German shepherd dogs is due to combined pituitary hormone deficiency of unknown genetic cause. We localized the recessively inherited defect by a genome wide approach to a region on chromosome 9 with a lod score of 9.8. The region contains LHX3, which codes for a transcription factor essential for pituitary development. Dwarfs have a deletion of one of six 7 bp repeats in intron 5 of LHX3, reducing the intron size to 68 bp. One dwarf was compound heterozygous for the deletion and an insertion of an asparagine residue in the DNA-binding homeodomain of LHX3, suggesting involvement of the gene in the disorder. An exon trapping assay indicated that the shortened intron is not spliced efficiently, probably because it is too small. We applied bisulfite conversion of cytosine to uracil in RNA followed by RT-PCR to analyze the splicing products. The aberrantly spliced RNA molecules resulted from either skipping of exon 5 or retention of intron 5. The same splicing defects were observed in cDNA derived from the pituitary of dwarfs. A survey of similarly mutated introns suggests that there is a minimal distance requirement between the splice donor and branch site of 50 nucleotides. In conclusion, a contraction of a DNA repeat in intron 5 of canine LHX3 leads to deficient splicing and is associated with pituitary dwarfism.

  13. Neutral Sphingomyelinase (SMPD3) Deficiency Causes a Novel Form of Chondrodysplasia and Dwarfism That Is Rescued by Col2A1-Driven smpd3 Transgene Expression

    Science.gov (United States)

    Stoffel, Wilhelm; Jenke, Britta; Holz, Barbara; Binczek, Erika; Günter, Robert Heinz; Knifka, Jutta; Koebke, Jürgen; Niehoff, Anja

    2007-01-01

    Neutral sphingomyelinase SMPD3 (nSMase2), a sphingomyelin phosphodiesterase, resides in the Golgi apparatus and is ubiquitously expressed. Gene ablation of smpd3 causes a generalized prolongation of the cell cycle that leads to late embryonic and juvenile hypoplasia because of the SMPD3 deficiency in hypothalamic neurosecretory neurons. We show here that this novel form of combined pituitary hormone deficiency is characterized by the perturbation of the hypothalamus-pituitary growth axis, associated with retarded chondrocyte development and enchondral ossification in the epiphyseal growth plate. To study the contribution by combined pituitary hormone deficiency and by the local SMPD3 deficiency in the epiphyseal growth plate to the skeletal phenotype, we introduced the full-length smpd3 cDNA transgene under the control of the chondrocyte-specific promoter Col2a1. A complete rescue of the smpd3−/− mouse from severe short-limbed skeletal dysplasia was achieved. The smpd3−/− mouse shares its dwarf and chondrodysplasia phenotype with the most common form of human achondrodysplasia, linked to the fibroblast-growth-factor receptor 3 locus, not linked to deficits in the hypothalamic-pituitary epiphyseal growth plate axis. The rescue of smpd3 in vivo has implications for future research into dwarfism and, particularly, growth and development of the skeletal system and for current screening and future treatment of combined dwarfism and chondrodysplasia. PMID:17591962

  14. Reduced ability of C-type natriuretic peptide (CNP) to activate natriuretic peptide receptor B (NPR-B) causes dwarfism in lbab−/− mice

    Science.gov (United States)

    Yoder, Andrea R.; Kruse, Andrew C.; Earhart, Cathleen A.; Ohlendorf, Douglas H.; Potter, Lincoln R.

    2015-01-01

    C-type natriuretic peptide (CNP) stimulates endochondrial ossification by activating the transmembrane guanylyl cyclase, natriuretic peptide receptor-B (NPR-B). Recently, a spontaneous autosomal recessive mutation that causes severe dwarfism in mice was identified. The mutant, called long bone abnormality (lbab), contains a single point mutation that converts an arginine to a glycine in a conserved coding region of the CNP gene, but how this mutation affects CNP activity has not been reported. Here, we determined that thirty to greater than one hundred-fold more CNPlbab was required to activate NPR-B as compared to wild-type CNP in whole cell cGMP elevation and membrane guanylyl cyclase assays. The reduced ability of CNPlbab to activate NPR-B was explained, at least in part, by decreased binding since ten-fold more CNPlbab than wild-type CNP was required to compete with [125I][Tyr0]CNP for receptor binding. Molecular modeling suggested that the conserved arginine is critical for binding to an equally conserved acidic pocket in NPR-B. These results indicate that reduced binding to and activation of NPR-B causes dwarfism in lbab−/− mice. PMID:18554750

  15. Correlation Analysis Between Expression Levels of Hepatic Growth Hormone Receptor, Janus Kinase 2, Insulin-Like Growth Factor-I Genes and Dwarfism Phenotype in Bama Minipig.

    Science.gov (United States)

    Yang, Haowen; Jiang, Qinyang; Wu, Dan; Lan, Ganqiu; Fan, Jing; Guo, Yafen; Chen, Baojian; Yang, Xiurong; Jiang, Hesheng

    2015-02-01

    Animal growth and development are complex and sophisticated biological metabolic processes, in which genes plays an important role. In this paper, we employed real-time quantitative PCR (RT-qPCR) to analyze the expression levels of hepatic GHR, JAK2 and IGF-I genes in 1, 30, 180 day of Bama minipig and Landrace with attempt to verify the correlation between the expression of these growth-associated genes and the dwarfism phenotype of Bama minipig. The results showed that the expression levels of these 3 genes in Bama minipigs were down-regulated expressed from 1 day to 30 day, and which was up-regulated expressed in Landrace. The expression levels of the 3 genes on 1, 30, 180 day were prominently higher in Landrace than in Bama minipigs. The significant differences of the 3 genes expression levels on 1 day between this two breeds indicate that different expressions of these genes might occur before birth. It is speculated that the down-regulated expression of the 3 genes may have a close correlation with the dwarfism phenotype of Bama minipig. More investigations in depth of this study is under progress with the help of biochip nanotechnology.

  16. A Contracted DNA Repeat in LHX3 Intron 5 Is Associated with Aberrant Splicing and Pituitary Dwarfism in German Shepherd Dogs

    Science.gov (United States)

    Voorbij, Annemarie M. W. Y.; van Steenbeek, Frank G.; Vos-Loohuis, Manon; Martens, Ellen E. C. P.; Hanson-Nilsson, Jeanette M.; van Oost, Bernard A.; Kooistra, Hans S.; Leegwater, Peter A.

    2011-01-01

    Dwarfism in German shepherd dogs is due to combined pituitary hormone deficiency of unknown genetic cause. We localized the recessively inherited defect by a genome wide approach to a region on chromosome 9 with a lod score of 9.8. The region contains LHX3, which codes for a transcription factor essential for pituitary development. Dwarfs have a deletion of one of six 7 bp repeats in intron 5 of LHX3, reducing the intron size to 68 bp. One dwarf was compound heterozygous for the deletion and an insertion of an asparagine residue in the DNA-binding homeodomain of LHX3, suggesting involvement of the gene in the disorder. An exon trapping assay indicated that the shortened intron is not spliced efficiently, probably because it is too small. We applied bisulfite conversion of cytosine to uracil in RNA followed by RT-PCR to analyze the splicing products. The aberrantly spliced RNA molecules resulted from either skipping of exon 5 or retention of intron 5. The same splicing defects were observed in cDNA derived from the pituitary of dwarfs. A survey of similarly mutated introns suggests that there is a minimal distance requirement between the splice donor and branch site of 50 nucleotides. In conclusion, a contraction of a DNA repeat in intron 5 of canine LHX3 leads to deficient splicing and is associated with pituitary dwarfism. PMID:22132174

  17. Striking hematological abnormalities in patients with microcephalic osteodysplastic primordial dwarfism type II (MOPD II): a potential role of pericentrin in hematopoiesis.

    Science.gov (United States)

    Unal, Sule; Alanay, Yasemin; Cetin, Mualla; Boduroglu, Koray; Utine, Eda; Cormier-Daire, Valerie; Huber, Celine; Ozsurekci, Yasemin; Kilic, Esra; Simsek Kiper, Ozlem Pelin; Gumruk, Fatma

    2014-02-01

    Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a rare primordial dwarfism that is similar to Seckel syndrome. Seckel syndrome is known to be associated with various hematological abnormalities; however, hematological findings in MOPD II patients have not been previously reported. The present study aimed to describe the hematological findings in a series of eight patients with MOPD II from a single center. The study included eight patients with MOPD II that were analyzed via molecular testing, and physical and laboratory examinations. Molecular testing showed that seven of the eight patients had pericentrin (PCNT) gene mutations. Hematological evaluation showed that 7 (87.5%) patients had thrombocytosis, 6 (75%) had leukocytosis, 5 (62.5%) had both leukocytosis and thrombocytosis, and 2 (25%) had anemia. We report leukocytosis and thrombocytosis as a common hematologic abnormality in patients with MOPD II. The present findings may improve our understanding of the potential function of the PCNT gene in hematopoietic cell proliferation and differentiation. © 2013 Wiley Periodicals, Inc.

  18. Nanismo hipofisário em um canino: achados clínicos e laboratoriais Pituitary dwarfism in a canine: clinical and laboratorial findings

    Directory of Open Access Journals (Sweden)

    Luiz Fernando Jantzen Gaspar

    1995-01-01

    Full Text Available Relata-se um caso de nanismo hipofisário em um canino da raça Pastor Alemão, fêmea, com 14 meses de idade. Descreve-se sinais clínicos e dosagem das concentrações plasmáticas de hormônio do crescimento (GH antes e após a estimulação α-adrenιrgica com cloridrato de xilazina. O nível máximo de GH plasmático pós-estímulo foi 1ng/dl.This case report is about dwarfism in a German Shepherd dog, female, 14 months old. Clinical signals are described. The endocrinologic investigation was realized by dosages of plasma levels of growth hormone, pré and post xilazine estimulation. The maximal level of GH post-estimulation was 1ng/dl.

  19. Overexpression of Galnt3 in chondrocytes resulted in dwarfism due to the increase of mucin-type O-glycans and reduction of glycosaminoglycans.

    Science.gov (United States)

    Yoshida, Carolina Andrea; Kawane, Tetsuya; Moriishi, Takeshi; Purushothaman, Anurag; Miyazaki, Toshihiro; Komori, Hisato; Mori, Masako; Qin, Xin; Hashimoto, Ayako; Sugahara, Kazuyuki; Yamana, Kei; Takada, Kenji; Komori, Toshihisa

    2014-09-19

    Galnt3, UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3, transfers N-acetyl-D-galactosamine to serine and threonine residues, initiating mucin type O-glycosylation of proteins. We searched the target genes of Runx2, which is an essential transcription factor for chondrocyte maturation, in chondrocytes and found that Galnt3 expression was up-regulated by Runx2 and severely reduced in Runx2(-/-) cartilaginous skeletons. To investigate the function of Galnt3 in chondrocytes, we generated Galnt3(-/-) mice and chondrocyte-specific Galnt3 transgenic mice under the control of the Col2a1 promoter-enhancer. Galnt3(-/-) mice showed a delay in endochondral ossification and shortened limbs at embryonic day 16.5, suggesting that Galnt3 is involved in chondrocyte maturation. Galnt3 transgenic mice presented dwarfism, the chondrocyte maturation was retarded, the cell cycle in chondrocytes was accelerated, premature chondrocyte apoptosis occurred, and the growth plates were disorganized. The binding of Vicia villosa agglutinin, which recognizes the Tn antigen (GalNAc-O-Ser/Thr), was drastically increased in chondrocytes, and aggrecan (Acan) was highly enriched with Tn antigen. However, safranin O staining, which recognizes glycosaminoglycans (GAGs), and Acan were severely reduced. Chondroitin sulfate was reduced in amount, but the elongation of chondroitin sulfate chains had not been severely disturbed in the isolated GAGs. These findings indicate that overexpression of Galnt3 in chondrocytes caused dwarfism due to the increase of mucin-type O-glycans and the reduction of GAGs, probably through competition with xylosyltransferases, which initiate GAG chains by attaching O-linked xylose to serine residues, suggesting a negative effect of Galnt family proteins on Acan deposition in addition to the positive effect of Galnt3 on chondrocyte maturation. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Molecular analysis of pericentrin gene (PCNT) in a series of 24 Seckel/microcephalic osteodysplastic primordial dwarfism type II (MOPD II) families.

    Science.gov (United States)

    Willems, M; Geneviève, D; Borck, G; Baumann, C; Baujat, G; Bieth, E; Edery, P; Farra, C; Gerard, M; Héron, D; Leheup, B; Le Merrer, M; Lyonnet, S; Martin-Coignard, D; Mathieu, M; Thauvin-Robinet, C; Verloes, A; Colleaux, L; Munnich, A; Cormier-Daire, V

    2010-12-01

    Microcephalic osteodysplastic primordial dwarfism type II (MOPD II, MIM 210720) and Seckel syndrome (SCKL, MIM 210600) belong to the primordial dwarfism group characterised by intrauterine growth retardation, severe proportionate short stature, and pronounced microcephaly. MOPD II is distinct from SCKL by more severe growth retardation, radiological abnormalities, and absent or mild mental retardation. Seckel syndrome is associated with defective ATR dependent DNA damage signalling. In 2008, loss-of-function mutations in the pericentrin gene (PCNT) have been identified in 28 patients, including 3 SCKL and 25 MOPDII cases. This gene encodes a centrosomal protein which plays a key role in the organisation of mitotic spindles. The aim of this study was to analyse PCNT in a large series of SCKL-MOPD II cases to further define the clinical spectrum associated with PCNT mutations. Among 18 consanguineous families (13 SCKL and 5 MOPDII) and 6 isolated cases (3 SCKL and 3 MOPD II), 13 distinct mutations were identified in 5/16 SCKL and 8/8 MOPDII including five stop mutations, five frameshift mutations, two splice site mutations, and one apparent missense mutation affecting the last base of exon 19. Moreover, we demonstrated that this latter mutation leads to an abnormal splicing with a predicted premature termination of translation. The clinical analysis of the 5 SCKL cases with PCNT mutations showed that they all presented minor skeletal changes and clinical features compatible with MOPDII diagnosis. It is therefore concluded that, despite variable severity, MOPDII is a genetically homogeneous condition due to loss-of-function of pericentrin.

  1. Dwarfism (For Parents)

    Science.gov (United States)

    ... Health Growth & Development Infections Diseases & Conditions Pregnancy & Baby Nutrition & Fitness Emotions & Behavior School & Family Life First Aid & ... legs trouble with joint flexibility and early arthritis lower back pain or leg numbness crowding of teeth Not every ...

  2. Experimental reproduction of beak atrophy and dwarfism syndrome by infection in cherry valley ducklings with a novel goose parvovirus-related parvovirus.

    Science.gov (United States)

    Chen, Hao; Dou, Yanguo; Tang, Yi; Zheng, Xiaoqiang; Niu, Xiaoyu; Yang, Jing; Yu, Xianglong; Diao, Youxiang

    2016-02-01

    Infection of clinically susceptible ducks, including cherry valley and Muscovy ducks, with a novel goose parvovirus (GPV)-related virus (N-GPV) can result in beak atrophy and dwarfism syndrome (BADS). To obtain new insights into the host range and pathogenic potential of this novel waterfowl parvovirus, cherry valley ducklings (n=20) were experimentally infected with N-GPV strain SDLC01. An equal number of ducklings served as uninfected controls. The appearance of clinical signs, histopathological changes, viral shedding, and seroconversion was monitored for 20 days post-infection. Infection status of all ducks was monitored using indirect ELISA, virus neutralization test, nested PCR, clinical indicators, and microscopic examination. Three ducks developed the typical clinical, gross, and histological changes of BADS. By study day 6, the infected ducks had seroconverted to N-GPV. The antibodies raised were neutralizing against the SDLC01 strain in vitro. Here we successfully developed an experimental infection model for studying the pathogenicity and role of N-GPV in BADS. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Expanding the phenotype of alopecia-contractures-dwarfism mental retardation syndrome (ACD syndrome): description of an additional case and review of the literature.

    Science.gov (United States)

    Schell-Apacik, Chayim; Hardt, Michael; Ertl-Wagner, Birgit; Klopocki, Eva; Möhrenschlager, Matthias; Heinrich, Uwe; von Voss, Hubertus

    2008-09-01

    Alopecia-contractures-dwarfism mental retardation syndrome (ACD syndrome; OMIM 203550) is a very rare genetic disorder with distinct features. To our knowledge, there have been four cases documented to date. In addition, another three patients, previously described as having IFAP syndrome (OMIM %308205), may also have ACD syndrome. We report on one patient with short stature, total alopecia, ichthyosis, photophobia, seizures, ectrodactyly, vertebral anomalies, scoliosis, multiple contractures, mental retardation, and striking facial and other features (e.g. microdolichocephaly, missing eyebrows and eyelashes, long nose, large ears) consistent with ACD syndrome. Results of laboratory testing in the literature case reports were normal, although in none of them, array-CGH (microarray-based comparative genomic hybridization) analysis was performed. In conclusion, the combination of specific features, including total alopecia, ichthyosis, mental retardation, and skeletal anomalies are suggestive of ACD syndrome. We propose that children with this syndrome undergo a certain social pediatric protocol including EEG diagnostics, ophthalmological investigation, psychological testing, management of dermatologic and orthopedic problems, and genetic counseling.

  4. Isolation and characterization of a distinct duck-origin goose parvovirus causing an outbreak of duckling short beak and dwarfism syndrome in China.

    Science.gov (United States)

    Chen, Shilong; Wang, Shao; Cheng, Xiaoxia; Xiao, Shifeng; Zhu, Xiaoli; Lin, Fengqiang; Wu, Nanyang; Wang, Jinxiang; Huang, Meiqing; Zheng, Min; Chen, Shaoying; Yu, Fusong

    2016-09-01

    Many mule duck and Cherry Valley duck flocks in different duck-producing regions of China have shown signs of an apparently new disease designated "short beak and dwarfism syndrome" (SBDS) since 2015. The disease is characterized by dyspraxia, weight loss, a protruding tongue, and high morbidity and low mortality rates. In order to characterize the etiological agent, a virus designated SBDSV M15 was isolated from allantoic fluid of dead embryos following serial passage in duck embryos. This virus causes a cytopathic effect in duck embryo fibroblast (DEF) cells. Using monoclonal antibody diagnostic assays, the SBDSV M15 isolate was positive for the antigen of goose parvovirus but not Muscovy duck parvovirus. A 348-bp (2604-2951) VP1gene fragment was amplified, and its sequence indicated that the virus was most closely related to a Hungarian GPV strain that was also isolated from mule ducks with SBDS disease. A similar disease was reproduced by inoculating birds with SBDSV M15. Together, these data indicate that SBDSV M15 is a GPV-related parvovirus causing SBDS disease and that it is divergent from classical GPV isolates.

  5. Cartilage-Specific and Cre-Dependent Nkx3.2 Overexpression In Vivo Causes Skeletal Dwarfism by Delaying Cartilage Hypertrophy.

    Science.gov (United States)

    Jeong, Da-Un; Choi, Je-Yong; Kim, Dae-Won

    2017-01-01

    Nkx3.2, the vertebrate homologue of Drosophila bagpipe, has been implicated as playing a role in chondrogenic differentiation. In brief, Nkx3.2 is initially expressed in chondrocyte precursor cells and later during cartilage maturation, its expression is diminished in hypertrophic chondrocytes. In addition to Nkx3.2 expression analyses, previous studies using ex vivo chick embryo cultures and in vitro cell cultures have suggested that Nkx3.2 can suppress chondrocyte hypertrophy. However, it has never been demonstrated that Nkx3.2 functions in regulating chondrocyte hypertrophy during cartilage development in vivo. Here, we show that cartilage-specific and Cre-dependent Nkx3.2 overexpression in mice results in significant postnatal dwarfism in endochondral skeletons, while intramembranous bones remain unaltered. Further, we observed significant delays in cartilage hypertrophy in conditional transgenic ciTg-Nkx3.2 mice. Together, these findings confirm that Nkx3.2 is capable of controlling hypertrophic maturation of cartilage in vivo, and this regulation plays a significant role in endochondral ossification and longitudinal bone growth. J. Cell. Physiol. 232: 78-90, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Identification of two novel critical mutations in PCNT gene resulting in microcephalic osteodysplastic primordial dwarfism type II associated with multiple intracranial aneurysms.

    Science.gov (United States)

    Li, Fei-Feng; Wang, Xu-Dong; Zhu, Min-Wei; Lou, Zhi-Hong; Zhang, Qiong; Zhu, Chun-Yu; Feng, Hong-Lin; Lin, Zhi-Guo; Liu, Shu-Lin

    2015-12-01

    Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a highly detrimental human autosomal inherited recessive disorder. The hallmark characteristics of this disease are intrauterine and postnatal growth restrictions, with some patients also having cerebrovascular problems such as cerebral aneurysms. The genomic basis behind most clinical features of MOPD II remains largely unclear. The aim of this work was to identify the genetic defects in a Chinese family with MOPD II associated with multiple intracranial aneurysms. The patient had typical MOPD II syndrome, with subarachnoid hemorrhage and multiple intracranial aneurysms. We identified three novel mutations in the PCNT gene, including one single base alteration (9842A>C in exon 45) and two deletions (Del-C in exon 30 and Del-16 in exon 41). The deletions were co-segregated with the affected individual in the family and were not present in the control population. Computer modeling demonstrated that the deletions may cause drastic changes on the secondary and tertiary structures, affecting the hydrophilicity and hydrophobicity of the mutant proteins. In conclusion, we identified two novel mutations in the PCNT gene associated with MOPD II and intracranial aneurysms, and the mutations were expected to alter the stability and functioning of the protein by computer modeling.

  7. Loss of function mutation in LARP7, chaperone of 7SK ncRNA, causes a syndrome of facial dysmorphism, intellectual disability, and primordial dwarfism.

    Science.gov (United States)

    Alazami, Anas M; Al-Owain, Mohammad; Alzahrani, Fatema; Shuaib, Taghreed; Al-Shamrani, Hussain; Al-Falki, Yahya H; Al-Qahtani, Saleh M; Alsheddi, Tarfa; Colak, Dilek; Alkuraya, Fowzan S

    2012-10-01

    Primordial dwarfism (PD) is a clinically and genetically heterogeneous condition. Various molecular mechanisms are known to underlie the disease including impaired mitotic mechanics, abnormal IGF2 expression, perturbed DNA damage response, defective spliceosomal machinery, and abnormal replication licensing. Here, we describe a syndromic form of PD associated with severe intellectual disability and distinct facial features in a large multiplex Saudi family. Analysis reveals a novel underlying mechanism for PD involving depletion of 7SK, an abundant cellular noncoding RNA (ncRNA), due to mutation of its chaperone LARP7. We show that 7SK levels are tightly linked to LARP7 expression across cell lines, and that this chaperone is ubiquitously expressed in the mouse embryo. The 7SK is known to influence the expression of a wide array of genes through its inhibitory effect on the positive transcription elongation factor b (P-TEFb) as well as its competing role in HMGA1-mediated transcriptional regulation. This study documents a critical role played by ncRNA in human development and adds to the growing list of molecular mechanisms that, when perturbed, converge on the PD phenotype. © 2012 Wiley Periodicals, Inc.

  8. A homozygous mutation in RNU4ATAC as a cause of microcephalic osteodysplastic primordial dwarfism type I (MOPD I) with associated pigmentary disorder.

    Science.gov (United States)

    Abdel-Salam, Ghada M H; Miyake, Noriko; Eid, Maha M; Abdel-Hamid, Mohamed S; Hassan, Nihal A; Eid, Ola M; Effat, Laila K; El-Badry, Tarek H; El-Kamah, Ghada Y; El-Darouti, Mohamed; Matsumoto, Naomichi

    2011-11-01

    The designation microcephalic osteodysplastic primordial dwarfism (MOPD) refers to a group of autosomal recessive disorders, comprising microcephaly, growth retardation, and a skeletal dysplasia. The different types of MOPD have been delineated on the basis of clinical, radiological, and genetic criteria. We describe two brothers, born to healthy, consanguineous parents, with intrauterine and postnatal growth retardation, microcephaly with abnormal gyral pattern and partial agenesis of corpus callosum, and skeletal anomalies reminiscent of those described in MOPD type I. This was confirmed by the identification of the homozygous g.55G > A mutation of RNU4ATAC encoding U4atac snRNA. The sibs had yellowish-gray hair, fair skin, and deficient retinal pigmentation. Skin biopsy showed abnormal melanin function but OCA genes were normal. The older sib had an intracranial hemorrhage at 1 week after birth, the younger developed chilblains-like lesions at the age 2½ years old but analysis of the SAMHD1 and TREX1 genes did not show any mutations. To the best of our knowledge, vasculopathy and pigmentary disorders have not been reported in MOPD I. Copyright © 2011 Wiley Periodicals, Inc.

  9. The test results and analysis of bone mineral density in adult dwarfism%成人侏儒症患者骨密度检测结果及分析

    Institute of Scientific and Technical Information of China (English)

    普英; 陈水英; 普蔼君; 蒋家望

    2013-01-01

    目的 检测成人侏儒症患者腰椎、右髋、左髋骨密度值,与正常同龄人体检组相比较,探讨成人侏儒症患者与骨质疏松的相关性.方法 采用法国MEDI MINK公司生产的OSTEOCORE 3双能X线骨密度检测仪检测28例成人侏儒症患者腰椎、左髋、右髋骨密度,求出均值,以最低值作为诊断依据,并随机选出38例体检的正常同龄人与之比对.结果 患病组与对照组两组相比,年龄无差异,P=0.13>0.005;身高有显著性差异,P=0.000<0.005;体重有显著性差异,P=0.000<0.005;腰椎骨密度均值有显著性差异,P=0.000<0.005;右髋骨密度均值有显著性差异,P=0.000<0.005;左髋骨密度均值有显著性差异,P=0.000< 0.005.28例侏儒症患者中骨量正常0例,占0%、骨量减少4例,占14.29%、骨质疏松24例,占85.71%、其中骨质疏松中达严重骨质疏松者12例.结论 成人侏儒症患者骨量减少合骨质疏松患病率达100%,无一例骨密度正常,要高度重视这一特殊人群的骨髂健康.%Objective To measure the bone mineral density of the lumbar vertebrae,the right iliac,and the left iliac in adult patients with dwarfism,comparing that with normal people of the same age,and to investigate the correlation between adult dwarfism and osteoporosis.Methods The bone mineral density of the lumbar vertebrae,the right iliac,and the left iliac were measured in 28 adult patients with dwarfism using Osteocore 3 dual-energy X-ray absorptiometry (MED MINK Co.,France).The mean value was calculated and the lowest value was set as diagnosis criteria.Meanwhile,38 normal people of the same age were randomly selected.The bone mineral density was also measured and compared.Results There was no significant difference of age between 2 groups (P > 0.05),while both the height and the weight in two groups showed significant difference (P < 0.005).The bone mineral density of the lumbar vertebrae,the right iliac,and the left iliac

  10. Diversion of carbon flux from gibberellin to steviol biosynthesis by over-expressing SrKA13H induced dwarfism and abnormality in pollen germination and seed set behaviour of transgenic Arabidopsis.

    Science.gov (United States)

    Guleria, Praveen; Masand, Shikha; Yadav, Sudesh Kumar

    2015-07-01

    This paper documents the engineering of Arabidopsis thaliana for the ectopic over-expression of SrKA13H (ent-kaurenoic acid-13 hydroxylase) cDNA from Stevia rebaudiana. HPLC analysis revealed the significant accumulation of steviol (1-3 μg g(-1) DW) in two independent transgenic Arabidopsis lines over-expressing SrKA13H compared with the control. Independent of the steviol concentrations detected, both transgenic lines showed similar reductions in endogenous bioactive gibberellins (GA1 and GA4). They possessed phenotypic similarity to gibberellin-deficient mutants. The reduction in endogenous gibberellin content was found to be responsible for dwarfism in the transgenics. The exogenous application of GA3 could rescue the transgenics from dwarfism. The hypocotyl, rosette area, and stem length were all considerably reduced in the transgenics. A noteworthy decrease in pollen viability was noticed and, similarly, a retardation of 60-80% in pollen germination rate was observed. The exogenous application of steviol (0.2, 0.5, and 1.0 μg ml(-1)) did not influence pollen germination efficiency. This has suggested that in planta formation of steviol was not responsible for the observed changes in transgenic Arabidopsis. Further, the seed yield of the transgenics was reduced by 24-48%. Hence, this study reports for the first time that over-expression of SrKA13H cDNA in Arabidopsis has diverted the gibberellin biosynthetic route towards steviol biosynthesis. The Arabidopsis transgenics showed a significant reduction in endogenous gibberellins that might be responsible for the dwarfism, and the abnormal behaviour of pollen germination and seed set.

  11. Suppression of γ-aminobutyric acid (GABA) transaminases induces prominent GABA accumulation, dwarfism and infertility in the tomato (Solanum lycopersicum L.).

    Science.gov (United States)

    Koike, Satoshi; Matsukura, Chiaki; Takayama, Mariko; Asamizu, Erika; Ezura, Hiroshi

    2013-05-01

    Tomatoes accumulate γ-aminobutyric acid (GABA) at high levels in the immature fruits. GABA is rapidly converted to succinate during fruit ripening through the activities of GABA transaminase (GABA-T) and succinate semialdehyde dehydrogenase (SSADH). Although three genes encoding GABA-T and both pyruvate- and α-ketoglutarate-dependent GABA-T activities have been detected in tomato fruits, the mechanism underlying the GABA-T-mediated conversion of GABA has not been fully understood. In this work, we conducted loss-of-function analyses utilizing RNA interference (RNAi) transgenic plants with suppressed pyruvate- and glyoxylate-dependent GABA-T gene expression to clarify which GABA-T isoforms are essential for its function. The RNAi plants with suppressed SlGABA-T gene expression, particularly SlGABA-T1, showed severe dwarfism and infertility. SlGABA-T1 expression was inversely associated with GABA levels in the fruit at the red ripe stage. The GABA contents in 35S::SlGABA-T1(RNAi) lines were 1.3-2.0 times and 6.8-9.2 times higher in mature green and red ripe fruits, respectively, than the contents in wild-type fruits. In addition, SlGABA-T1 expression was strongly suppressed in the GABA-accumulating lines. These results indicate that pyruvate- and glyoxylate-dependent GABA-T is the essential isoform for GABA metabolism in tomato plants and that GABA-T1 primarily contributes to GABA reduction in the ripening fruits.

  12. Dwarfism and Altered Craniofacial Development in Rabbits Is Caused by a 12.1 kb Deletion at the HMGA2 Locus.

    Science.gov (United States)

    Carneiro, Miguel; Hu, Dou; Archer, John; Feng, Chungang; Afonso, Sandra; Chen, Congying; Blanco-Aguiar, José A; Garreau, Hervé; Boucher, Samuel; Ferreira, Paula G; Ferrand, Nuno; Rubin, Carl-Johan; Andersson, Leif

    2017-02-01

    The dwarf phenotype characterizes the smallest of rabbit breeds and is governed largely by the effects of a single dwarfing allele with an incompletely dominant effect on growth. Dwarf rabbits typically weigh under 1 kg and have altered craniofacial morphology. The dwarf allele is recessive lethal and dwarf homozygotes die within a few days of birth. The dwarf phenotype is expressed in heterozygous individuals and rabbits from dwarf breeds homozygous for the wild-type allele are normal, although smaller when compared to other breeds. Here, we show that the dwarf allele constitutes a ∼12.1 kb deletion overlapping the promoter region and first three exons of the HMGA2 gene leading to inactivation of this gene. HMGA2 has been frequently associated with variation in body size across species. Homozygotes for null alleles are viable in mice but not in rabbits and probably not in humans. RNA-sequencing analysis of rabbit embryos showed that very few genes (4-29 genes) were differentially expressed among the three HMGA2/dwarf genotypes, suggesting that dwarfism and inviability in rabbits are caused by modest changes in gene expression. Our results show that HMGA2 is critical for normal expression of IGF2BP2, which encodes an RNA-binding protein. Finally, we report a catalog of regions of elevated genetic differentiation between dwarf and normal-size rabbits, including LCORL-NCAPG, STC2, HOXD cluster, and IGF2BP2 Levels and patterns of genetic diversity at the LCORL-NCAPG locus further suggest that small size in dwarf breeds was enhanced by crosses with wild rabbits. Overall, our results imply that small size in dwarf rabbits results from a large effect, loss-of-function (LOF) mutation in HMGA2 combined with polygenic selection. Copyright © 2017 by the Genetics Society of America.

  13. Genetic analysis and gibberellins treatment effects on dwarfism of maize genic male sterile mutant induced by space flight%太空诱变玉米核不育突变体矮化的遗传及外施赤霉素分析

    Institute of Scientific and Technical Information of China (English)

    汪静; 程江; 曹墨菊

    2016-01-01

    Male sterility provides an effective way for maize hybrids production. Plant dwarfism is one of the important target traits in crop breeding. Maize research institute of Sichuan Agricultural University obtained a genic male sterile mutant induced by space flight which was controlled by a pair of recessive genes. This mutant has the traits of sterility and dwarfism both needed by breeding. In order to find the genetic rules and reasons of dwarfism of the maize genic male sterile mutant, taking this sterile mutant as mother and inbred lines 178, 478 as father, fertility identification and plant height analysis of test cross F1 , F2 , genotype and plant height analysis of fertile F2 , fertility identification and plant height, tassel length, internode number and internode length analysis of sister cross off-springs were done. Meanwhile, gibberellins were applied on sister cross off-springs, fertility and plant height of which were examined. The results were as follows: The plant height difference of F1 at the background of 178 and 478 which was significant was the same with that between 178 and 478; Sterile plant height was significantly lower than fertile plant height in F2 at the background of 178 or 478, and the difference of sterile plant heights was not significant in F2 at the background of 178 and 478, while the difference of fertile plant heights was significant; In fertile F2 at the background of 178 or 478 of which the off-springs’ fertility separated, the difference between homozygous and heterozygous plant heights was all not significant; In sister cross off-springs, separation ratio of fertile and sterile plants met 1 ∶ 1, and sterile plant height, tassel length, in-ternode number and internode length were significantly less to those of fertile plant; Exogenous application of gibberellins did not affect the fertility of sterile plants, and the sterile plants showed certain sensitivity to gibberellins at seedling stage, but the plant height of which

  14. Effect of recombinant insulin-like growth factor-1 treatment on short-term linear growth in a child with Majewski osteodysplastic primordial dwarfism type II and hepatic insufficiency.

    Science.gov (United States)

    Faienza, Maria Felicia; Acquafredda, Angelo; D'Aniello, Mariangela; Soldano, Lucia; Marzano, Flaviana; Ventura, Annamaria; Cavallo, Luciano

    2013-01-01

    We report the case of a boy affected by severe intrauterine and postnatal growth retardation, microcephaly, facial dysmorphisms and postnecrotic cirrhosis, diagnosed at birth as having Seckel syndrome, and subsequently confirmed as Majewski osteodysplastic primordial dwarfism type II (MOPD II) on the basis of clinical and radiological features of skeletal dysplasia. At our observation (6 years 7 months) he presented height -10.3 standard deviation score (SDS), weight -22.1 SDS, head circumference -8 SDS, delayed bone age of 4 years with respect to chronological age. In consideration of the low levels of insulin-like growth factor-1 (IGF-1) as well as of hepatic insufficiency, we started the treatment with recombinant human IGF-1 (rhIGF-1) at the dose of 0.04 mg/kg in 2 doses/day, with an increase of 0.04 mg/kg after 1 week until the maximum dose of 0.12 mg/kg. We observed an early response to rhIGF-1 treatment, with a shift of height velocity from 1.8 cm/year (-4.6 SDS) at 4 cm/year (-1.9 SDS), and an increase in bone age of 1.5 years during the first 6 months. rhIGF-1 treatment does not seem to be able to replace the physiological action of IGF-1 in patients with MOPD II and hepatic insufficiency, however, it seems to preserve the typical growth pattern of MOPD II patients, avoiding a further widening of the growth deficiency in these subjects.

  15. Melhoramento do trigo: II. Estudo genético de fontes de nanismo para a cultura do trigo Wheat breeding II: genetic studies of different sources of dwarfism in wheat

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo de Oliveira Camargo

    1981-01-01

    Itararé Experimental Station. All data were determined on an individual plant basis. It was observed partial dominance for tall plants when Siete Cerros, Vicam-71 and Olesen were crossed with IAC-5 and partial dominance for short plants when Tordo was crossed with IAC-5. Broad sense herltability for plant height and grain yield showed high and low values, respectively. Narrow sense heritability and coefficient of determination for plant height were high. Narrow sense heritability for grain yield was low. Results suggest it would be possible to select plant types with semi-dwarf and dwarf height levels in the F2 or Fa populations and for yield in later generations where progeny tests would be possible. Height and yield correlations were also computed for all crosses. In general the magnitude of the environmental, phenotypic and genetic correlations were high and consistent for all crosses. Segregating populations from crosses between the tall cultivar IAC-5 and different sources of dwarfism indicated that the short stature sources could be used efficiently in a breeding program toward the development of semi-dwarf or dwarf wheat cultivars with high yield potential. However, large F2 populations would be required to ensure the frequency of desired recombinants. Tordo would be the best source due to the heigher frequency of short statured individuals.

  16. Case of lethal congenital dwarfism with accelerated skeletal maturation

    Energy Technology Data Exchange (ETDEWEB)

    Blomstrand, S.; Claesson, I.; Saeve-Soederbergh, J.

    1985-02-01

    Details of a female infant, who was born after 29 weeks gestation and who died within minutes of birth, are presented. The infant was hydropic, showed macroglossia and had very short limbs with normal sized hands and feet. Apart from a preductal aortic coarctation the pathological findings were confined to the skeleton. The radiographical and histological findings are described in detail; they differ from those of previous studies of similar conditions.

  17. Mutations in the NHEJ component XRCC4 cause primordial dwarfism

    NARCIS (Netherlands)

    J.E. Murray (Jennie E.); M. van der Burg (Mirjam); H. IJspeert (Hanna); P. Carroll (Paula); Q. Wu (Qian); T. Ochi (Takashi); A. Leitch (Andrea); E.S. Miller (Edward S.); B. Kysela (Boris); A. Jawad (Alireza); A. Bottani (Armand); F. Brancati (Fred); M. Cappa (Marco); V. Cormier-Daire (Valerie); C. Deshpande (Charu); E.A. Faqeih (Eissa A.); G.E. Graham (Gail E.); E. Ranza (Emmanuelle); T.L. Blundell (Tom L.); A.P. Jackson (Andrew); G.S. Stewart (Grant S.); L.S. Bicknell (Louise)

    2015-01-01

    textabstractNon-homologous end joining (NHEJ) is a key cellular process ensuring genome integrity. Mutations in several components of the NHEJ pathway have been identified, often associated with severe combined immunodeficiency (SCID), consistent with the requirement for NHEJ during V(D)J

  18. Mutations in the pericentrin (PCNT) gene cause primordial dwarfism

    NARCIS (Netherlands)

    Rauch, Anita; Thiel, Christian T.; Schindler, Detlev; Wick, Ursula; Crow, Yanick J.; Ekici, Arif B.; van Essen, Anthonie J.; Goecke, Timm O.; Al-Gazali, Lihadh; Chrzanowska, Krystyna H.; Zweier, Christiane; Brunner, Han G.; Becker, Kristin; Curry, Cynthia J.; Dallapiccola, Bruno; Devriendt, Koenraad; Doerfler, Arnd; Kinning, Esther; Megarbane, Andre; Meinecke, Peter; Semple, Robert K.; Spranger, Stephanie; Toutain, Annick; Trembath, Richard C.; Voss, Egbert; Wilson, Louise; Hennekam, Raoul; de Zegher, Francis; Doerr, Helmuth-Guenther; Reis, Andre

    2008-01-01

    Fundamental processes influencing human growth can be revealed by studying extreme short stature. Using genetic linkage analysis, we find that biallelic loss- of- function mutations in the centrosomal pericentrin ( PCNT) gene on chromosome 21q22.3 cause microcephalic osteodysplastic primordial

  19. Bone histology indicates insular dwarfism in a new Late Jurassic sauropod dinosaur.

    Science.gov (United States)

    Sander, P Martin; Mateus, Octávio; Laven, Thomas; Knötschke, Nils

    2006-06-01

    Sauropod dinosaurs were the largest animals ever to inhabit the land, with truly gigantic forms in at least three lineages. Small species with an adult body mass less than five tonnes are very rare, and small sauropod bones generally represent juveniles. Here we describe a new diminutive species of basal macronarian sauropod, Europasaurus holgeri gen. et sp. nov., and on the basis of bone histology we show it to have been a dwarf species. The fossils, including excellent skull material, come from Kimmeridgian marine beds of northern Germany, and record more than 11 individuals of sauropods 1.7 to 6.2 m in total body length. Morphological overlap between partial skeletons and isolated bones links all material to the same new taxon. Cortical histology of femora and tibiae indicates that size differences within the specimens are due to different ontogenetic stages, from juveniles to fully grown individuals. The little dinosaurs must have lived on one of the large islands around the Lower Saxony basin. Comparison with the long-bone histology of large-bodied sauropods suggests that the island dwarf species evolved through a decrease in growth rate from its larger ancestor.

  20. Combined spinal–epidural anesthesia for an elderly patient with proportionate dwarfism for laparotomy

    Directory of Open Access Journals (Sweden)

    Teena Bansal

    2016-01-01

    Full Text Available Anesthesia in a dwarf patient may be challenging as various anatomical anomalies make both general and regional anesthesia difficult. These patients may have atlantoaxial instability, potential for airway obstruction, and associated respiratory problems that may pose problems for general anesthesia. Spinal stenosis, osteophytes, short pedicles, or a small epidural space could complicate regional anesthesia in dwarfs which could lead to difficulties in locating the epidural space and increase the risk of dural puncture. Spinal stenosis may impair cerebrospinal fluid flow such that identification of dural puncture is difficult. This elderly dwarf patient had history of bronchial asthma with restriction of neck extension, managed successfully using combined spinal–epidural anesthesia.

  1. Adaptive stress response in segmental progeria resembles long-lived dwarfism and calorie restriction in mice

    NARCIS (Netherlands)

    H.W.M. van de Ven (Marieke); J.-O. Andressoo (Jaan-Olle); V.B. Holcomb (Valerie); M.M. von Lindern (Marieke); W.M.C. Jong (Willeke); C.I. de Zeeuw (Chris); Y. Suh (Yousin); P. Hasty (Paul); J.H.J. Hoeijmakers (Jan); G.T.J. van der Horst (Gijsbertus); J.R. Mitchell (James)

    2006-01-01

    textabstractHow congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular senes

  2. Adaptive stress response in segmental progeria resembles long-lived dwarfism and calorie restriction in mice

    NARCIS (Netherlands)

    H.W.M. van de Ven (Marieke); J.-O. Andressoo (Jaan-Olle); V.B. Holcomb (Valerie); M.M. von Lindern (Marieke); W.M.C. Jong (Willeke); C.I. de Zeeuw (Chris); Y. Suh (Yousin); P. Hasty (Paul); J.H.J. Hoeijmakers (Jan); G.T.J. van der Horst (Gijsbertus); J.R. Mitchell (James)

    2006-01-01

    textabstractHow congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular senes

  3. Lemierre syndrome presenting as acute mastoiditis in a 2-year-old girl with congenital dwarfism

    Directory of Open Access Journals (Sweden)

    Jason B. Fischer

    2015-06-01

    Full Text Available Lemierre syndrome is defined by septic thrombophlebitis of the internal jugular vein caused by Fusobacterium. Historically, these infections originate from the oropharynx and typically are seen in older children, adolescents and young adults. More recently, otogenic sources in younger children have been described with increasing frequency. We present a case of a two-year old, who initially developed an otitis media with perforation of the tympanic membrane and went on to develop mastoiditis and non-occlusive thrombosis of the venous sinus and right internal jugular vein. Fusobacterium necrophorum was grown from operative cultures of the mastoid, ensuing computed tomography scan revealed occlusion of the internal jugular vein and the patient was successfully treated with clindamycin, ciprofloxacin and enoxaparin. This case demonstrates the importance of considering Fusobacterium in otogenic infections and the consideration of Lemierre syndrome when F. necrophorum is identified.

  4. Myxedematous cretinism with dwarfism or Spanish painting in doctor's collection and unforgettable French park

    Directory of Open Access Journals (Sweden)

    G A Melnichenko

    2010-12-01

    Full Text Available Долина королей, долина Луары – зачарованное место памятников истории и волшебных замков, удивительных садов и поразительных историй. В од- ном таком замке – Вилландри (http://www.chateauvillandry.fr/en неподалеку от Тура, переплелись французская история и история медицины. Своей нынешней славой замок обязан испанскому врачу Joachim Carvallo, родившемуся в Испании в 1869 г., прапрадедушке нынешнего владельца. Его медицинская карьера проходила в клинике профессора Charles Richet, нобелевского лауреата 1913 г. (работы по асфиксии, но после женитьбы он приобрел замок Вилландри, разместил там свою коллекцию испанской живописи и реализовал мечту о создании идеальных садов, жизни в гармонии с природой, среди посаженных человеком растений и деревьев в замке эпохи Ренессанса. Вероятно, контраст безмятежной красоты природы, и безупречной архитектуры, и трагического реализма испанских полотен был особенно важен доктору Корвалло, и среди его картин оказалась маленькая работа неизвестного автора, предположительно школы Гойи (рис.. Эта картина ранее не фигурировала, насколько мне известно, среди работ, описывающих те или иные изображения гипотиреоза и микседематозной карликовости, но нынешний владелец замка и директор музея Вилландри Henri Corvallo (Анри Корвалло любезно разрешил мне использовать репродукцию картины (и прислал ее для публикации и выразил удовлетворение тем, что теперь он сможет более точно атрибутировать конкретный тип карликовости изображенного на полотне лица. Надо сказать, что гипотиреоз, развившийся в зрелом возрасте, имеет много характерных черт, но для подтверждения диагноза, как бы ни была типична клиника, мы все равно сегодня будем исследовать ТТГ и св. Т4 и только после этого представим историю болезни на публикацию. Другое дело – изображения лиц с врожденным гипотиреозом, со всеми признаки фатальной задержки развития и роста, которые несет отсутствие жизненно необходимых тиреоидных гормонов. Изображенный человек не юн, и мы с уверенностью можем сказать, что он рожден не в нищей семье и за ним сохраняется уход. Пропорции его тела – иллюстрация из старых учебников о типичном внешнем виде не получавших лечение больных с врожденным гипотиреозом: непропорционально большая голова, западающая переносица, мален

  5. Clinical Spectrum of LIG4 Deficiency Is Broadened with Severe Dysmaturity, Primordial Dwarfism, and Neurological Abnormalities

    NARCIS (Netherlands)

    H. IJspeert (Hanna); A. Warris (Adilia); M. van der Flier (Michiel); I. Reisli (Ismail); S. Keles (Sevgi); S. Chishimba (Sandra); J.J.M. van Dongen (Jacques); D.C. van Gent (Dik); M. van der Burg (Mirjam)

    2013-01-01

    textabstractDNA double-strand break repair via non-homologous end joining (NHEJ) is involved in recombination of immunoglobulin and T-cell receptor genes. Mutations in NHEJ components result in syndromes that are characterized by microcephaly and immunodeficiency. We present a patient with

  6. Clinical Spectrum of LIG4 Deficiency Is Broadened with Severe Dysmaturity, Primordial Dwarfism, and Neurological Abnormalities.

    NARCIS (Netherlands)

    Ijspeert, H.; Warris, A.; Flier, M. van der; Reisli, I.; Keles, S.; Chishimba, S.; Dongen, J.J. van; Gent, D.C. van; Burg, M. van der

    2013-01-01

    DNA double-strand break repair via non-homologous end joining (NHEJ) is involved in recombination of immunoglobulin and T-cell receptor genes. Mutations in NHEJ components result in syndromes that are characterized by microcephaly and immunodeficiency. We present a patient with lymphopenia, extreme

  7. Dwarfism and increased adiposity in the gh1 mutant zebrafish vizzini.

    Science.gov (United States)

    McMenamin, Sarah K; Minchin, James E N; Gordon, Tiffany N; Rawls, John F; Parichy, David M

    2013-04-01

    Somatic growth and adipogenesis are closely associated with the development of obesity in humans. In this study, we identify a zebrafish mutant, vizzini, that exhibits both a severe defect in somatic growth and increased accumulation of adipose tissue. Positional cloning of vizzini revealed a premature stop codon in gh1. Although the effects of GH are largely through igfs in mammals, we found no decrease in the expression of igf transcripts in gh1 mutants during larval development. As development progressed, however, we found overall growth to be progressively retarded and the attainment of specific developmental stages to occur at abnormally small body sizes relative to wild type. Moreover, both subcutaneous (sc) and visceral adipose tissues underwent precocious development in vizzini mutants, and at maturity, the sizes of different fat deposits were greatly expanded relative to wild type. In vivo confocal imaging of sc adipose tissue (SAT) expansion revealed that vizzini mutants exhibit extreme enlargement of adipocyte lipid droplets without a corresponding increase in lipid droplet number. These findings suggest that GH1 signaling restricts SAT hypertrophy in zebrafish. Finally, nutrient deprivation of vizzini mutants revealed that SAT mobilization was greatly diminished during caloric restriction, further implicating GH1 signaling in adipose tissue homeostasis. Overall, the zebrafish gh1 mutant, vizzini, exhibits decreased somatic growth, increased adipose tissue accumulation, and disrupted adipose plasticity after nutrient deprivation and represents a novel model to investigate the in vivo dynamics of vertebrate obesity.

  8. Transient dwarfism of soil fauna during the Paleocene-Eocene Thermal Maximum

    Science.gov (United States)

    Smith, J.J.; Hasiotis, S.T.; Kraus, M.J.; Woody, D.T.

    2009-01-01

    Soil organisms, as recorded by trace fossils in paleosols of the Willwood Formation, Wyoming, show significant body-size reductions and increased abundances during the Paleocene-Eocene Thermal Maximum (PETM). Paleobotanical, paleopedologic, and oxygen isotope studies indicate high temperatures during the PETM and sharp declines in precipitation compared with late Paleocene estimates. Insect and oligochaete burrows increase in abundance during the PETM, suggesting longer periods of soil development and improved drainage conditions. Crayfish burrows and molluscan body fossils, abundant below and above the PETM interval, are significantly less abundant during the PETM, likely because of drier floodplain conditions and lower water tables. Burrow diameters of the most abundant ichnofossils are 30-46% smaller within the PETM interval. As burrow size is a proxy for body size, significant reductions in burrow diameter suggest that their tracemakers were smaller bodied. Smaller body sizes may have resulted from higher subsurface temperatures, lower soil moisture conditions, or nutritionally deficient vegetation in the high-CO2 atmosphere inferred for the PETM. Smaller soil fauna co-occur with dwarf mammal taxa during the PETM; thus, a common forcing mechanism may have selected for small size in both above- and below-ground terrestrial communities. We predict that soil fauna have already shown reductions in size over the last 150 years of increased atmospheric CO2 and surface temperatures or that they will exhibit this pattern over the next century. We retrodict also that soil fauna across the Permian-Triassic and Triassic-Jurassic boundary events show significant size decreases because of similar forcing mechanisms driven by rapid global warming.

  9. Adaptive stress response in segmental progeria resembles long-lived dwarfism and calorie restriction in mice

    NARCIS (Netherlands)

    H.W.M. van de Ven (Marieke); J.-O. Andressoo (Jaan-Olle); V.B. Holcomb (Valerie); M.M. von Lindern (Marieke); W.M.C. Jong (Willeke); C.I. de Zeeuw (Chris); Y. Suh (Yousin); P. Hasty (Paul); J.H.J. Hoeijmakers (Jan); G.T.J. van der Horst (Gijsbertus); J.R. Mitchell (James)

    2006-01-01

    textabstractHow congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular

  10. Growth Problems

    Science.gov (United States)

    ... that can lead to significantly short stature is dwarfism . Dwarfism results from abnormal growth of the bones and cartilage in the body. In many forms of dwarfism the person has abnormal body proportions, such as ...

  11. Genetics Home Reference: isolated growth hormone deficiency

    Science.gov (United States)

    ... Genetic Testing (4 links) Genetic Testing Registry: Ateleiotic dwarfism Genetic Testing Registry: Autosomal dominant isolated somatotropin deficiency ... in my area? Other Names for This Condition dwarfism, growth hormone deficiency dwarfism, pituitary growth hormone deficiency ...

  12. Elevated Fibroblast Growth Factor Signaling Is Critical for the Pathogenesis of the Dwarfism in Evc2/Limbin Mutant Mice

    OpenAIRE

    Zhang, Honghao; Kamiya, Nobuhiro; Tsuji, Takehito; Takeda, Haruko; Scott, Greg; Rajderkar, Sudha; Ray, Manas K.; Mochida, Yoshiyuki; Allen, Benjamin L.; Lefebvre, Veronique; Hung, Irene H.; Ornitz, David M.; Kunieda, Tetsuo; Mishina, Yuji

    2016-01-01

    Ellis-van Creveld (EvC) syndrome is a skeletal dysplasia, characterized by short limbs, postaxial polydactyly, and dental abnormalities. EvC syndrome is also categorized as a ciliopathy because of ciliary localization of proteins encoded by the two causative genes, EVC and EVC2 (aka LIMBIN). While recent studies demonstrated important roles for EVC/EVC2 in Hedgehog signaling, there is still little known about the pathophysiological mechanisms underlying the skeletal dysplasia features of EvC ...

  13. Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects

    DEFF Research Database (Denmark)

    Zhu, Xiaorong; Zhou, An; Dey, Arunangsu

    2002-01-01

    ., Rouille, Y., Holst, J., Carroll, R., Ravazzola, M., Orci, L., Furuta, H. & Steiner, D. (1997) Proc. Natl. Acad. Sci. USA 94, 6646-6651). The PC1/3-null mice differ from a human subject reported with compound heterozygosity for defects in this gene, who was of normal stature but markedly obese from early...... life. The PC1/3-null mice are not obese. The basis for these phenotypic differences is an interesting topic for further study. These findings prove the importance of PC1/3 as a key neuroendocrine convertase....

  14. Regulation of GAs-binding protein on dwarfism of rice (Oryza sativa L.)

    Institute of Scientific and Technical Information of China (English)

    SONGPing; CAOXianzu; WUYonghong; LIANGJiansheng

    1994-01-01

    The levels of endogenous hormones (GAs and ABA) in rice seedlings (7d) were measured by gas-liquid chromatography with flame ionization detoctor (GLC-FID) and the GAs-binding protein on meanbrane of young rice shoot was also analysed as dascribed by Chiharu.

  15. Short-limb dwarfism and hypertrophic cardiomyopathy in a patient with paternal isodisomy 14: 45,XYidic(14)(p11)

    Energy Technology Data Exchange (ETDEWEB)

    Walter, C.A.; Moore, C.M.; Kaye, C.I. [Univ. of Texas Health Science Center, San Antonio, TX (United States)] [and others

    1996-11-11

    Uniparental disomy (UPD) has been shown to result in specific disorders either due to imprinting and/or homozygosity of mutant alleles. Here we present the findings in a child with paternal UPD14. Ultrasound evaluation was performed at 30 weeks of gestation because of abnormally large uterine size. Pertinent ultrasound findings included polyhydramnios, short limbs, abnormal position of hands, small thorax, and nonvisualization of the fetal stomach. Postnatally the infant was found to have a low birth weight, short birth length, contractures, short limbs, and a small thorax with upslanting ribs. Assisted ventilation and gastrostomy were required. At age 6 months, the infant required hospitalization for hypertrophic cardiomyopathy which responded to Atenolol{reg_sign}. Initial cytogenetic studies demonstrated an apparently balanced de novo Robertsonian translocation involving chromosomes 14 and a karyotype designation of 45,XY,t(14q14q). No indication of mosaicism for trisomy 14 was observed in metaphase spreads prepared from peripheral blood lymphocytes or skin-derived fibroblasts. C-band and fluorescence in situ hybridization results demonstrated that the chromosome was dicentric. DNA analyses showed paternal uniparental isodisomy for chromosome 14. Based on the cytogenetic and DNA results a final karyotype designation of 45,XY,idic(14)(p11) was assigned to this infant with paternal isodisomy of chromosome 14. 41 refs., 5 figs., 2 tabs.

  16. periostin null mice exhibit dwarfism, incisor enamel defects, and an early-onset periodontal disease-like phenotype.

    Science.gov (United States)

    Rios, Hector; Koushik, Shrinagesh V; Wang, Haiyan; Wang, Jian; Zhou, Hong-Ming; Lindsley, Andrew; Rogers, Rhonda; Chen, Zhi; Maeda, Manabu; Kruzynska-Frejtag, Agnieszka; Feng, Jian Q; Conway, Simon J

    2005-12-01

    Periostin was originally identified as an osteoblast-specific factor and is highly expressed in the embryonic periosteum, cardiac valves, placenta, and periodontal ligament as well as in many adult cancerous tissues. To investigate its role during development, we generated mice that lack the periostin gene and replaced the translation start site and first exon with a lacZ reporter gene. Surprisingly, although periostin is widely expressed in many developing organs, periostin-deficient (peri(lacZ)) embryos are grossly normal. Postnatally, however, approximately 14% of the nulls die before weaning and all of the remaining peri(lacZ) nulls are severely growth retarded. Skeletal analysis revealed that trabecular bone in adult homozygous skeletons was sparse, but overall bone growth was unaffected. Furthermore, by 3 months, the nulls develop an early-onset periodontal disease-like phenotype. Unexpectedly, these mice also show a severe incisor enamel defect, although there is no apparent change in ameloblast differentiation. Significantly, placing the peri(lacZ) nulls on a soft diet that alleviated mechanical strain on the periodontal ligament resulted in a partial rescue of both the enamel and periodontal disease-like phenotypes. Combined, these data suggest that a healthy periodontal ligament is required for normal amelogenesis and that periostin is critically required for maintenance of the integrity of the periodontal ligament in response to mechanical stresses.

  17. Insulin-like growth factor type-1 receptor down-regulation associated with dwarfism in Holstein calves.

    Science.gov (United States)

    Blum, J W; Elsasser, T H; Greger, D L; Wittenberg, S; de Vries, F; Distl, O

    2007-10-01

    Perturbations in endocrine functions can impact normal growth. Endocrine traits were studied in three dwarf calves exhibiting retarded but proportionate growth and four phenotypically normal half-siblings, sired by the same bull, and four unrelated control calves. Plasma 3,5,3'-triiodothyronine and thyroxine concentrations in dwarfs and half-siblings were in the physiological range and responded normally to injected thyroid-releasing hormone. Plasma glucagon concentrations were different (dwarfs, controls>half-siblings; Pcontrols, Pcontrols, P=0.08). Responses of GH to xylazine and to a GH-releasing-factor analogue were similar in dwarfs and half-siblings. Relative gene expression of IGF-1, IGF-2, GH receptor (GHR), insulin receptor, IGF-1 type-1 and -2 receptors (IGF-1R, IGF-2R), and IGF binding proteins were measured in liver and anconeus muscle. GHR mRNA levels were different in liver (dwarfsdwarfism in studied calves.

  18. Dwarfism and impaired gut development in insulin-like growth factor II mRNA-binding protein 1-deficient mice

    DEFF Research Database (Denmark)

    Hansen, Thomas V O; Hammer, Niels A; Nielsen, Jacob

    2004-01-01

    Insulin-like growth factor II mRNA-binding protein 1 (IMP1) belongs to a family of RNA-binding proteins implicated in mRNA localization, turnover, and translational control. Mouse IMP1 is expressed during early development, and an increase in expression occurs around embryonic day 12.5 (E12.5). T...

  19. Disease: H00443 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00443 Osteoglophonic dysplasia (OD); Osteoglophonic dwarfism (OGD) Osteoglophonic ...dysplasia (OD) or osteoglophonic dwarfism (OGD) is an autosomal dominant disorder that has skeletal phenotyp

  20. The Simultaneous Repression of CCR and CAD, Two Enzymes of the Lignin Biosynthetic Pathway, Results in Sterility and Dwarfism in Arabidopsis thaliana

    Institute of Scientific and Technical Information of China (English)

    Johanne Thévenin; Brigitte Pollet; Bruno Letarnec; Luc Saulnier; Lionel Gissot; Alessandra Maia-Grondard; Catherine Lapierre; Lise Jouanina

    2011-01-01

    Cinnamoyl CoA reductase(CCR)and cinnamyl alcohol dehydrogenase(CAD)catalyze the last steps of monolignol biosynthesis.In Arabidopsis,one CCR gene(CCR1,At1g15950)and two CAD genes(CAD C At3g19450 and CAD D At4g34230)are involved in this pathway.A triple cad c cad d ccr1 mutant,named ccc,was obtained.This mutant displays a severe dwarf phenotype and male sterility.The lignin content in ccc mature stems is reduced to 50% of the wild-type level.In addition,stem lignin structure is severely affected,as shown by the dramatic enrichment in resistant inter-unit bonds and incorporation into the polymer of monolignol precursors such as coniferaldehyde,sinapaldehyde,and ferulic acid.Male sterility is due to the lack of lignification in the anther endothecium,which causes the failure of anther dehiscence and of pollen release.The ccc hypolignified stems accumulate higher amounts of flavonol glycosides,sinapoyl malate and feruloyl malate,which suggests a redirection of the phenolic pathway.Therefore,the absence of CAD and CCR,key enzymes of the monolignol pathway,has more severe consequences on the phenotype than the individual absence of each of them.Induction of another CCR(CCR2,At1g80820)and another CAD(CAD1,At4g39330)does not compensate the absence of the main CCR and CAD activities.This lack of CCR and CAD activities not only impacts lignification,but also severely affects the development of the plants.These consequences must be carefully considered when trying to reduce the lignin content of plants in order to facilitate the lignocellulose-to-bioethanol conversion process.

  1. Proportionate Dwarfism in Mice Lacking Heterochromatin Protein 1 Binding Protein 3 (HP1BP3) Is Associated With Alterations in the Endocrine IGF-1 Pathway.

    Science.gov (United States)

    Garfinkel, Benjamin P; Arad, Shiri; Le, Phuong T; Bustin, Michael; Rosen, Clifford J; Gabet, Yankel; Orly, Joseph

    2015-12-01

    Heterochromatin protein 1 binding protein 3 (HP1BP3) is a recently described histone H1-related protein with roles in chromatin structure and transcriptional regulation. To explore the potential physiological role of HP1BP3, we have previously described an Hp1bp3(-/-) mouse model with reduced postnatal viability and growth. We now find that these mice are proportionate dwarfs, with reduction in body weight, body length, and organ weight. In addition to their small size, microcomputed tomography analysis showed that Hp1bp3(-/-) mice present a dramatic impairment of their bone development and structure. By 3 weeks of age, mice of both sexes have severely impaired cortical and trabecular bone, and these defects persist into adulthood and beyond. Primary cultures of both osteoblasts and osteoclasts from Hp1bp3(-/-) bone marrow and splenocytes, respectively, showed normal differentiation and function, strongly suggesting that the impaired bone accrual is due to noncell autonomous systemic cues in vivo. One major endocrine pathway regulating both body growth and bone acquisition is the IGF regulatory system, composed of IGF-1, the IGF receptors, and the IGF-binding proteins (IGFBPs). At 3 weeks of age, Hp1bp3(-/-) mice exhibited a 60% reduction in circulating IGF-1 and a 4-fold increase in the levels of IGFBP-1 and IGFBP-2. These alterations were reflected in similar changes in the hepatic transcripts of the Igf1, Igfbp1, and Igfbp2 genes. Collectively, these results suggest that HP1BP3 plays a key role in normal growth and bone development by regulating transcription of endocrine IGF-1 components.

  2. A novel homologous model for gene therapy of dwarfism by non-viral transfer of the mouse growth hormone gene into immunocompetent dwarf mice.

    Science.gov (United States)

    Cecchi, Claudia R; Higuti, Eliza; Oliveira, Nelio A J; Lima, Eliana R; Jakobsen, Maria; Dagnaes-Hansen, Frederick; Gissel, Hanne; Aagaard, Lars; Jensen, Thomas G; Jorge, Alexander A L; Bartolini, Paolo; Peroni, Cibele N

    2014-02-01

    The possibilities for non-viral GH gene therapy are studied in immunocompetent dwarf mice (lit/lit). As expression vector we used a plasmid previously employed in immunodeficient dwarf mice (pUBI-hGH-gDNA) by replacing the human GH gene with the genomic sequence of mouse-GH DNA (pUBI-mGH-gDNA). HEK-293 human cells transfected with pUBI-mGH-gDNA produced 3.0 µg mGH/10(6) cells/day compared to 3.7 µg hGH/10(6) cells/day for pUBIhGH- gDNA transfected cells. The weight of lit/lit mice treated with the same two plasmids (50 µg DNA/mouse) by electrotransfer into the quadriceps muscle was followed for 3 months. The weight increase up to 15 days for mGH, hGH and saline treated mice were 0.130, 0.112 and 0.027 g/mouse/day. Most sera from hGH-treated mice contained anti-hGH antibodies already on day 15, with the highest titers on day 45, while no significant anti-mGH antibodies were observed in mGH-treated mice. At the end of 3 months, the weight increase for mGH-treated mice was 34.3%, while the nose-to-tail and femur lengths increased 9.5% and 24.3%. Mouse-GH and hGH circulating levels were 4-5 ng/mL 15 days after treatment, versus control levels of ~0.7 ng GH/mL (P<0.001). In mGH-treated mice, mIGF-I determined on days 15, 45 and 94 were 1.5- to 3-fold higher than the control and 1.2- to 1.6-fold higher than hGH-treated mice. The described homologous model represents an important progress forming the basis for preclinical testing of non-viral gene therapy for GH deficiency.

  3. Paleodigms and paleodigmatics: a new theoretical construct applicable to Munchausen's syndrome by proxy, child-abuse dwarfism, paraphilias, anorexia nervosa, and other syndromes.

    Science.gov (United States)

    Money, J

    1989-01-01

    A paleodigm is a formulation of ancient folk wisdom that encodes a causal explanation in a saying or story that penetrates the idiom of everyday language and influences behavior. Although paleodigms are not, per se, causative, they have diagnostic, prognostic, and therapeutic significance in syndromes like Munchausen's syndrome by proxy.

  4. A novel dwarfism with gonadal dysfunction due to loss-of-function allele of the collagen receptor gene, Ddr2, in the mouse.

    Science.gov (United States)

    Kano, Kiyoshi; Marín de Evsikova, C; Young, James; Wnek, Christopher; Maddatu, Terry P; Nishina, Patsy M; Naggert, Jürgen K

    2008-08-01

    Smallie (slie), a spontaneous, autosomal-recessive mutation causes dwarfing and infertility in mice. The purpose of this study was to determine and characterize the underlying molecular genetic basis for its phenotype. The slie locus was mapped to chromosome 1, and fine-structure mapping narrowed the slie allele within 2 Mb between genetic markers D1Mit36 and Mpz. To pinpoint the underlying mutation quantitative real-time PCR was used to measure the relative expression levels for the genes residing within this region. Expression of one gene, Ddr2, which encodes discoidin domain receptor 2 (DDR2), was absent in slie homozygote mice. Genomic sequencing analysis detected a 150-kb deletion that extended into the Ddr2 gene transcript. Detailed phenotype analysis revealed that gonadal dysregulation underlies infertility in slie mice because all females were anovulatory and most adult males lacked spermatogenesis. The pituitary gland of prepubertal slie mice was smaller than in wild-type mice. The basal levels and gene expression for pituitary and hypothalamic hormones, and gene expression for hypothalamic-releasing hormones, were not significantly different between slie and wild-type mice. Circulating levels of IGF-1 did not differ in slie mice despite lower Igf-1 mRNA expression in the liver. After exogenous gonadotropin administration, the levels of secreted steroid hormones in both male and female adult slie mice were blunted compared to adult wild-type, but was similar to prepubertal wild-type mice. Taken together, our results indicate that the absence of DDR2 leads to growth retardation and gonadal dysfunction due to peripheral defects in hormonal-responsive pathways in slie mice.

  5. Genetics Home Reference: spondylothoracic dysostosis

    Science.gov (United States)

    ... normal-length arms and legs, called short-trunk dwarfism. The spine and rib abnormalities, which are present ... Additional Information & Resources MedlinePlus (2 links) Health Topic: Dwarfism Health Topic: Spine Injuries and Disorders Genetic and ...

  6. Genetics Home Reference: osteoglophonic dysplasia

    Science.gov (United States)

    ... leads to severe head and face (craniofacial) abnormalities, dwarfism, and other features. The term osteoglophonic refers to ... and Management Resources (1 link) Seattle Children's Hospital: Dwarfism and Bone Dysplasias General Information from MedlinePlus (5 ...

  7. Genetics Home Reference: spondyloepimetaphyseal dysplasia, Strudwick type

    Science.gov (United States)

    ... of bone growth that results in short stature (dwarfism), skeletal abnormalities, and problems with vision. This condition ... Scoliosis Health Topic: Connective Tissue Disorders Health Topic: Dwarfism Genetic and Rare Diseases Information Center (1 link) ...

  8. Genetics Home Reference: Schimke immuno-osseous dysplasia

    Science.gov (United States)

    ... 4 links) Health Topic: Bone Diseases Health Topic: Dwarfism Health Topic: Immune System and Disorders Health Topic: ... Immune Deficiency Conditions University of Kansas Medical Center: Dwarfism/Short Stature GeneReviews (1 link) Schimke Immunoosseous Dysplasia ...

  9. Genetics Home Reference: 3-M syndrome

    Science.gov (United States)

    ... syndrome is a disorder that causes short stature (dwarfism), unusual facial features, and skeletal abnormalities. The name ... Additional Information & Resources MedlinePlus (1 link) Health Topic: Dwarfism Genetic and Rare Diseases Information Center (1 link) ...

  10. Genetics Home Reference: cartilage-hair hypoplasia

    Science.gov (United States)

    ... disorder of bone growth characterized by short stature (dwarfism) with other skeletal abnormalities; fine, sparse hair ( hypotrichosis ); ... Additional Information & Resources MedlinePlus (1 link) Health Topic: Dwarfism Genetic and Rare Diseases Information Center (1 link) ...

  11. Achondroplasia

    Science.gov (United States)

    ... growth that causes the most common type of dwarfism. Causes Achondroplasia is one of a group of ... the condition. Symptoms The typical appearance of achondroplastic dwarfism can be seen at birth. Symptoms may include: ...

  12. Genetics Home Reference: metatropic dysplasia

    Science.gov (United States)

    ... is a skeletal disorder characterized by short stature (dwarfism) with other skeletal abnormalities. The term "metatropic" is ... my area? Other Names for This Condition metatropic dwarfism metatropic dysplasia type 1 Related Information How are ...

  13. Genetics Home Reference: hypochondroplasia

    Science.gov (United States)

    ... Description Hypochondroplasia is a form of short-limbed dwarfism. This condition affects the conversion of cartilage into ... Resources MedlinePlus (2 links) Encyclopedia: Lordosis Health Topic: Dwarfism Genetic and Rare Diseases Information Center (1 link) ...

  14. Genetics Home Reference: Kniest dysplasia

    Science.gov (United States)

    ... disorder of bone growth characterized by short stature (dwarfism) with other skeletal abnormalities and problems with vision ... for This Condition Kniest chondrodystrophy Kniest syndrome Metatropic dwarfism, type II Metatropic dysplasia type II Swiss cheese ...

  15. Genetics Home Reference: anauxetic dysplasia

    Science.gov (United States)

    ... is a disorder characterized by extremely short stature (dwarfism) and other skeletal abnormalities, an unusually large range ... in this disorder. People with anauxetic dysplasia have dwarfism with unusually short limbs for their height (disproportionate ...

  16. Genetics Home Reference: achondroplasia

    Science.gov (United States)

    ... Description Achondroplasia is a form of short-limbed dwarfism. The word achondroplasia literally means "without cartilage formation." ... is the most common type of short-limbed dwarfism. The condition occurs in 1 in 15,000 ...

  17. Genetics Home Reference: campomelic dysplasia

    Science.gov (United States)

    ... my area? Other Names for This Condition campomelic dwarfism campomelic syndrome camptomelic dysplasia Related Information How are ... Robin Syndrome Health Topic: Bone Diseases Health Topic: Dwarfism Genetic and Rare Diseases Information Center (1 link) ...

  18. Genetics Home Reference: spondyloepiphyseal dysplasia congenita

    Science.gov (United States)

    ... bone growth disorder that results in short stature (dwarfism), skeletal abnormalities, and problems with vision and hearing. ... Diseases Health Topic: Connective Tissue Disorders Health Topic: Dwarfism Genetic and Rare Diseases Information Center (1 link) ...

  19. Genetics Home Reference: thanatophoric dysplasia

    Science.gov (United States)

    ... Other Names for This Condition Dwarf, thanatophoric thanatophoric dwarfism thanatophoric short stature Related Information How are genetic ... 3 links) Health Topic: Craniofacial Abnormalities Health Topic: Dwarfism Health Topic: Respiratory Failure Genetic and Rare Diseases ...

  20. Genetics Home Reference: geleophysic dysplasia

    Science.gov (United States)

    ... my area? Other Names for This Condition geleophysic dwarfism Related Information How are genetic conditions and genes ... and Rare Diseases Information Center (1 link) Geleophysic dwarfism Educational Resources (8 links) American Heart Association: Atrial ...

  1. Basics on Genes and Genetic Disorders

    Science.gov (United States)

    ... ay-kon-druh-PLAY-zhuh, a form of dwarfism), Marfan syndrome (a connective tissue disorder), and Huntington ... Parents MORE ON THIS TOPIC Albinism Muscular Dystrophy Dwarfism Marfan Syndrome Cystic Fibrosis Hemophilia von Willebrand Disease ...

  2. Disease: H00993 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H00993 Microcephalic osteodysplastic primordial dwarfism, type I (MOPD I); Taybi-Li...nder syndrome Microcephalic osteodysplastic primordial dwarfism, type I (MOPD I) is a condition comprising s...S, Philip N Microcephalic osteodysplastic primordial dwarfism Taybi-Linder type: report of four cases and re... GY, El-Darouti M, Matsumoto N A homozygous mutation in RNU4ATAC as a cause of microcephalic osteodysplastic primordial dwarfism...j V Microcephalic osteodysplastic primordial dwarfism with severe microdontia and skin anomalies: confirmation of a new syndrome. Am J Med Genet A 130A:181-90 (2004) ...

  3. Akromegali Dan Gigantisme

    OpenAIRE

    Silvani, Melati; Pase, M. Aron; Syafril, Santi; Lindarto, Dharma; Solin, Steffie S

    2016-01-01

    Hormon pertumbuhan manusia (Growth Hormone/GH) merupakan peptida rantai tunggal yang terdiri dari 191 asam amino, yang diisolasi dari sel somatotrop pada kelenjar hipofisis anterior pada tahun 1956, dan pertama kali digunakan sebagai terapi untuk penatalaksanaan dwarfisme hipofisis pada tahun 1958. Dwarfisme hipofisis adalah bentuk klasik dari defisiensi hormon pertumbuhan pada anak-anak Melati Silvani

  4. Reference: 67 [Arabidopsis Phenome Database[Archive

    Lifescience Database Archive (English)

    Full Text Available death2 (agd2-1) mutant has elevated levels of the defense signal salicylic acid (SA), altered leaf morphology, and mild dwarfism...vated SA content and a majority of the disease resistance and dwarfism of agd2-1.

  5. A Comparative Study of Computer-Aided Clinical Diagnosis of Birth Defects.

    Science.gov (United States)

    1981-01-21

    HYPOMAGNESEMIA TYPE PRIMARY HYPOPARATHYROIDISM TYPE X LINKED INFANTILE HYPOPHOSPHATASIA HYPOPHOSPHATEMIA JUVENILE DIABETES MELLITUS JUVENILE DIABETES MELLITUS... DIABETES INSIPIDUS TYPE VASOPRESSIN RESISTANT DWARFISM TYPE PANHYPOPITUITARY ENDOCRINE NEOPLASIA I TYPE MULTIPLE ENDOCRINE NEOPLASIA II TYPE MULTIPLE

  6. Genetics Home Reference: otospondylomegaepiphyseal dysplasia

    Science.gov (United States)

    ... the body that this condition affects: the ears (oto-), the bones of the spine (spondylo-), and the ... dwarfism Nance-Insley syndrome Nance-Sweeney chondrodysplasia OSMED oto-spondylo-megaepiphyseal dysplasia Related Information How are genetic ...

  7. Meier-Gorlin syndrome

    NARCIS (Netherlands)

    Munnik, S.A. de; Hoefsloot, E.H.; Roukema, J.; Schoots, J.; Knoers, N.V.A.M.; Brunner, H.G.; Jackson, A.P.; Bongers, E.M.H.F.

    2015-01-01

    Meier-Gorlin syndrome (MGS) is a rare autosomal recessive primordial dwarfism disorder, characterized by microtia, patellar applasia/hypoplasia, and a proportionate short stature. Associated clinical features encompass feeding problems, congenital pulmonary emphysema, mammary hypoplasia in females

  8. Meier-Gorlin syndrome Clinical genetics and genomics

    NARCIS (Netherlands)

    S. de Munnik (Sonja); E.H. Hoefsloot (Elisabeth H.); J. Roukema (Jolt); J. Schoots (Jeroen); N.V.A.M. Knoers (Nine); H.G. Brunner; A.P. Jackson (Andrew); E. Bongers (Ernie)

    2015-01-01

    textabstractMeier-Gorlin syndrome (MGS) is a rare autosomal recessive primordial dwarfism disorder, characterized by microtia, patellar applasia/hypoplasia, and a proportionate short stature. Associated clinical features encompass feeding problems, congenital pulmonary emphysema, mammary hypoplasia

  9. Meier-Gorlin syndrome Clinical genetics and genomics

    NARCIS (Netherlands)

    De Munnik, Sonja A.; Hoefsloot, Elisabeth H.; Roukema, Jolt; Schoots, Jeroen; Knoers, Nine Vam; Brunner, Han G.; Jackson, Andrew P.; Bongers, Ernie Mhf

    2015-01-01

    Meier-Gorlin syndrome (MGS) is a rare autosomal recessive primordial dwarfism disorder, characterized by microtia, patellar applasia/hypoplasia, and a proportionate short stature. Associated clinical features encompass feeding problems, congenital pulmonary emphysema, mammary hypoplasia in females

  10. Ellis Von Creveld Syndrome

    Directory of Open Access Journals (Sweden)

    Afshar H

    1999-01-01

    Full Text Available One patient with Ellis Von Creveld syndrome contains: dwarfism, congenital heart"ndisease, ectodermal dysplasia, polyductyly, an abnormally wide labial frenum and maxillary"nmolars with single root.

  11. Disease: H00873 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available haracterized by scapular and pelvic hypoplasia along with epiphyseal abnormalities, congenital dwarfism, and facial...S, Steinwender C, Scherer G, Spranger J, Zabel B, Kispert A, Superti-Furga A TBX15 mutations cause craniofacial

  12. Growth Hormone Treatment in Achondroplasia

    National Research Council Canada - National Science Library

    Hiroyuki Tanaka

    2003-01-01

    Abstract Achondroplasia is the most common short-limb dwarfism. Since the approval of GH treatment for the short stature in achondroplasia in 1997, 444 patients have been registered in the database...

  13. Cockayne syndrome

    DEFF Research Database (Denmark)

    Karikkineth, Ajoy C; Scheibye-Knudsen, Morten; Fivenson, Elayne;

    2017-01-01

    Cockayne syndrome (CS) is a disorder characterized by a variety of clinical features including cachectic dwarfism, severe neurological manifestations including microcephaly and cognitive deficits, pigmentary retinopathy, cataracts, sensorineural deafness, and ambulatory and feeding difficulties...

  14. Meier-Gorlin syndrome Clinical genetics and genomics

    NARCIS (Netherlands)

    De Munnik, Sonja A.; Hoefsloot, Elisabeth H.; Roukema, Jolt; Schoots, Jeroen; Knoers, Nine Vam; Brunner, Han G.; Jackson, Andrew P.; Bongers, Ernie Mhf

    2015-01-01

    Meier-Gorlin syndrome (MGS) is a rare autosomal recessive primordial dwarfism disorder, characterized by microtia, patellar applasia/hypoplasia, and a proportionate short stature. Associated clinical features encompass feeding problems, congenital pulmonary emphysema, mammary hypoplasia in females a

  15. Meier-Gorlin syndrome

    NARCIS (Netherlands)

    Munnik, S.A. de; Hoefsloot, E.H.; Roukema, J.; Schoots, J.; Knoers, N.V.A.M.; Brunner, H.G.; Jackson, A.P.; Bongers, E.M.H.F.

    2015-01-01

    Meier-Gorlin syndrome (MGS) is a rare autosomal recessive primordial dwarfism disorder, characterized by microtia, patellar applasia/hypoplasia, and a proportionate short stature. Associated clinical features encompass feeding problems, congenital pulmonary emphysema, mammary hypoplasia in females a

  16. Meier-Gorlin syndrome Clinical genetics and genomics

    NARCIS (Netherlands)

    S. de Munnik (Sonja); E.H. Hoefsloot (Elisabeth H.); J. Roukema (Jolt); J. Schoots (Jeroen); N.V.A.M. Knoers (Nine); H.G. Brunner; A.P. Jackson (Andrew); E. Bongers (Ernie)

    2015-01-01

    textabstractMeier-Gorlin syndrome (MGS) is a rare autosomal recessive primordial dwarfism disorder, characterized by microtia, patellar applasia/hypoplasia, and a proportionate short stature. Associated clinical features encompass feeding problems, congenital pulmonary emphysema, mammary hypoplasia

  17. Spondylometaphyseal dysplasia with hypercalcemia. [Radiological studies

    Energy Technology Data Exchange (ETDEWEB)

    Bagga, A.; Srivastava, R.N.; Gupta, S.; Gupta, A.

    1989-08-01

    Kozlowski's spondylometaphyseal dysplasia is characterised by short-trunk dwarfism, platyspondyly, metaphyseal dysplasia and retarded bone age. We report an association of this syndrome with asymptomatic, hypocalciuric hypercalcemia, a previously undocumented finding. (orig.).

  18. Microcephalin and pericentrin regulate mitotic entry via centrosome-associated Chk1

    DEFF Research Database (Denmark)

    Tibelius, Alexandra; Marhold, Joachim; Zentgraf, Hanswalter

    2009-01-01

    Primary microcephaly, Seckel syndrome, and microcephalic osteodysplastic primordial dwarfism type II (MOPD II) are disorders exhibiting marked microcephaly, with small brain sizes reflecting reduced neuron production during fetal life. Although primary microcephaly can be caused by mutations...

  19. Disease: H00474 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available rasound Obstet Gynecol 24:575-7 (2004) PMID:11200994 (de... (description) Varkey JJ, Jones RA Perinatally lethal, short-limbed dwarfism with distinct features -- Schneckenbecken dysplasia. Ult

  20. Anaesthetic management of a parturient with Laron syndrome.

    Science.gov (United States)

    Bhatia, K; Cockerham, R

    2011-10-01

    We report a case of a parturient with Laron syndrome, a rare form of dwarfism which results from an inability to generate insulin-like growth factor 1. In addition to dwarfism these patients may have craniofacial abnormalities, atlantoaxial instability, spinal stenosis and metabolic, musculoskeletal and genitourinary abnormalities. The patient underwent an urgent caesarean section using combined spinal-epidural anaesthesia. Laron syndrome is reviewed and its anaesthetic implications discussed.

  1. Disease: H00992 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available rized by intrauterine growth retardation, proportionate postnatal dwarfism, severe microcephaly, micrognathia, and 'bird-hea...Muthu MS, Saraswathi K, Koteeswaran D Bird-headed dwarf of Seckel. J Indian Soc Pedod Prev Dent 25 Suppl:S8-...ijer MF Microcephaly, micrognathia, and bird-headed dwarfism: prenatal diagnosis ...PMID:18157127 (description, gene) Griffith E, Walker S, Martin CA, Vagnarelli P, Stiff T, Vernay B, Al Sanna

  2. Ellis Van Creveld syndrome

    Directory of Open Access Journals (Sweden)

    Shilpy S

    2007-05-01

    Full Text Available Ellis Van Creveld syndrome is a rare disorder and is a form of short-limbed dwarfism. It is an autosomal recessive disorder characterized by tetrad of disproportionate dwarfism, post-axial polydactyly, ectodermal dysplasia and heart defects. This case report presents a classical case of a seven-year-old boy with Ellis Van Creveld syndrome presented with discrete clinical findings.

  3. Melhoramento do trigo: XX. Herdabilidades e correlações entre os componentes de produção em populações híbridas envolvendo fontes de nanismo Wheat breeding: XX. Heritabilities and correlations among yield components in hybrid populations involving different sources of dwarfism

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo de Oliveira Camargo

    1989-01-01

    Full Text Available Foram estimados os valores da herdabilidade em sentido restrito para a produção de grãos, altura das plantas, número de espigas por planta e de grãos por espiga e peso de cem grãos, bem como as correlações entre esses parâmetros através de cruzamentos em forma dialética entre os cultivares BH-1146, Atlas-66, Tordo e Siete Cerros. Plantas representando os pais, as gerações F1 e F2 e os retrocruzamentos para ambos os pais foram estudadas em um ensaio em blocos ao acaso, com cinco repetições, na Estação Experimental de Hyslop, da Universidade Estadual de Oregon, EUA, em 1978. Os valores da herdabilidade em sentido restrito para altura das plantas foram moderadamente altos para os cruzamentos BH-1146 x Atlas-66 (0,55, BH-1146 x Siete Cerros (0,60 e Atlas-66 x Siete Cerros (0,74; moderados para os cruzamentos Atlas-66 x Tordo (0,43 e Tordo x Siete Cerros (0,41, e baixo para o BH-1146 x Tordo (0,24. Foram estimados valores médios da herdabilidade em sentido restrito para número de espigas por planta variando de 0,43 a 0,58 para todos os cruzamentos, com exceção do BH-1146 x Atlas-66 e Atlas-66 x Tordo, que apresentaram valores baixos. Para o caráter peso de cem grãos, os indices da herdabilidade foram baixos para todos os cruzamentos, à exceção do BH-1146 x Atlas-66 e BH-1146 x Siete Cerros, que foram médios (0,40 e 0,45 respectivamente. Os valores da herdabilidade para produção de grãos foram baixos, à exceção dos verificados para os cruzamentos BH-1146 x Tordo (0,73 e BH-1146 x Siete Cerros (0,62. As correlações fenotípicas entre a produção de grãos e o número de espigas por planta, a altura das plantas, o número de grãos por espiga e o peso de cem grãos foram positivas e altamente significativas (com exceção da correlação produção de grãos e peso de cem grãos para a população BH-1146 x Atlas-66, que foi não-significativa. Os resultados sugerem ser possível selecionar somente plantas de porte semi-anão, com elevado potencial produtivo, alto número de grãos por espiga e de espigas por planta e elevado peso de cem grãos, desde que grandes populações segregantes sejam conduzidas para favorecer a identificação dos genótipos desejáveis originários das eventuais recombinações genéticas. Tal procedimento vem sendo adotado na seleção de cultivares de porte semi-anão para o Estado de São Paulo.Diallelic crosses were made involving the standard height cultivars BH-1146 and Atlas-66, the semidwarf cultivar Siete Cerros and the dwarf source Tordo. Parents, F1's, F2's and reciprocal backcrosses were tested for grain yield, plant height, number of heads per plant, number of kernels per head, and for weight of 100 kernels, in an experiment carried out at Hyslop Farm, Oregon, U.S.A., in 1978. Narrow sense heritability estimates for plant height were moderately high for the crosses BH-1146 x Atlas-66 (0.55, BH-1146 x Siete Cerros (0.60 and Atlas-66 x Siete Cerros (0.74, moderate for the crosses Atlas-66 x Tordo (0.43 and Tordo x Siete Cerros (0.41 and low for the cross BH-1146 x Tordo (0.24. Moderate values (0.43 to 0.58 were estimated for number of heads per plant for all crosses with exception of the crosses BH-1146 x Atlas-66 and Atlas-66 x Tordo which presented low values for the narrow sense heritability. The heritability values for weight of 100 grains were low for all crosses with exception of the crosses BH-1146 x Atlas-66 and BH-1146 x Siete Cerros which presented moderate levels (0.40 and 0.45, respectively. In relation to grain yield the narrow sense heritability estimates were low with exception of those for the crosses BH-1146 x Tordo (0.73 and BH-1146 x Siete Cerros (0.62. The phenotypic correlations between grain yield and number of heads per plant, plant height, number of grains per head and weight of 100 grains were positive and mostly highly significant, except for the correlation between grain yield and weight of 100 grains for the population BH-1146 x Atlas-66, which was not significant. The results suggested that it would be possible to select semidwarf plants, with high yield potential, with high number of kernels per head and heads per plant, and 100 kernel weight if large segregating populations are used to identify desired genotypes originated from eventual genetic recombinations. This procedure is being used for selections of semidwarf wheat cultivars in the State of São Paulo, Brazil.

  4. Melhoramento do trigo: VIII. Associações entre produção de grãos e outros caracteres agronômicos em populações híbridas envolvendo diferentes fontes de nanismo Wheat breeding: VIII. Associations of grain yield with other agronomic characteristics in crosses involving different sources of dwarfism in wheat

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo de Oliveira Camargo

    1984-01-01

    Full Text Available Foram estimados os valores da herdabilidade para várias características da planta do trigo (comprimento da espiga, número de espiguetas por espiga, número de grãos por espiga e de grãos por espigueta, peso de cem grãos, número de espigas por planta, altura das plantas e produção de grãos, bem como as correlações entre produção de grãos e os demais caracteres agronômicos. Os estudos foram realizados em cruzamentos entre o cultivar C-3, de porte alto, e os cultivares Tordo, Vican-71 e Olesen, de porte anão, e 'Siete Cerros', de porte semi-anão. Sementes representando os pais e as gerações F1 e F2 e os retrocruzamentos para ambos os pais foram utilizados em um ensaio, em blocos ao acaso, com quatro repetições, conduzido na Estação Experimental de Itararé, do Instituto Agronômico. Os dados foram coletados na base de plantas individuais. A herdabilidade no sentido amplo, para número de espiguetas por espiga e altura das plantas foi, respectivamente, 0,533 e 0,525, enquanto para comprimento da espiga, número de grãos por espiga e de grãos por espigueta, peso de cem grãos e número de espigas por planta, os valores observados variaram de 0,339 a 0,473. Para produção de grãos a estimativa obtida da herdabilidade no sentido amplo foi 0,255. Os valores da herdabilidade no sentido restrito, para os caracteres estudados, com exceção do número de espigas por planta, mostraram que grande parte da variabilidade de origem genética encontrada nas populações está também associada a uma ação aditiva dos genes. As correlações fenotípicas entre a produção de grãos e todos os demais caracteres agronômicos foram positivas e significativas ao nível de 1% para quase todas as populações estudadas. Constituíram exceções as correlações fenotípicas entre produção de grãos e número de espiguetas por espiga para as populações C-3 x Siete Cerros e C-3 x Vican-71; entre produção de grãos e peso de cem grãos para a população C-3 x Siete Cerros, e entre produção de grãos e número de grãos por espigueta para as populações C-3 x Siete Cerros, C-3 x Tordo, e C-3 x Olesen, que foram também positivas, porém significativas apenas ao nível de 5%.Standard height cultivar C-3 was crossed with the semi-dwarf cultivar Siete Cerros and the dwarf cultivars Tordo, Vican-71 and Olesen. Parents, F1's, F2's and reciprocal back-crosses were tested for grain yield, plant height, number of spikes per plant, number of spikelets per spike, number of grains per spike, number of grains per spikelet, 100-grain-weight, spike length, in a experiment carried out at Itararé Experimental Station, State of São Paulo, Brazil. All data was determined on an individual plant basis. Broad sense heritability estimates for number of spikelets per spike and plant height were 0.533 and 0.525, respectively. The values for spike length, number of grains per spike and spikelet, 100-grain-weight and number of spikes per plant showed variation between 0.339 and 0.473. Broad sense heritability for grain yield was low and equal to 0.255. Narrow sense heritability estimates for all characteristics under study except for number of spikes per plant showed that great part of the total genetic variation found in the studied populations was associated with additive gene action. The correlations between grain yield and all the other characteristics were positive and significant at 1% level probability, for all the populations under study, except for the correlations between grain yield and number of spikelets per spike for the populations C-3 x Siete Cerros and C-3 x Vican-71, between grain yield and 100-grain-weight for the population C-3 x Siete Cerros, between grains yield and number of grains per spikelet for the populations C-3 x Siete Cerros, C-3 x Tordo and C-3 x Olesen, which showed to be positive and significant only at the 5% probability level.

  5. The CI findings of 6 cases of the pineal cyst. Consideration on neuroradiological images and the mechanism of occurrence of pineal cysts in childhood

    Energy Technology Data Exchange (ETDEWEB)

    Nakajou, Takahito; Kurisaka, Masahiro; Mori, Koreaki [Kochi Medical School, Nankoku (Japan)

    1995-03-01

    In comparison to adult individuals over the age of 50, pineal cysts do rarely occur in children and adolescents. Here we report on four young patients who had pineal cysts in combination with hypophyseal dwarfism. We studied an 8-year-old girl with chiasmal germinoma, an 8-year-old boy with epilepsy, a 17-year-old male with spontaneous hypophyseal dwarfism and a 11-year-old female with craniopharyngioma. We also investigated a 29-year-old man with pontine glioma and a 48-year-old women with prolactinoma. The comparison of neuroimaging the pineal cysts in children and adults revealed the characteristics of their location in the pineal gland and the presence of residual normal gland. The etiology of pineal cysts in combination with pituitary dwarfism is unclear. However, our cases would suggest that they may be related to endocrinological disorders of the hypothalamus and the pituitary gland. (author).

  6. Prenatal diagnosis of lethal osteogenesis imperfecta in twin pregnancy.

    Science.gov (United States)

    Morin, L R; Herlicoviez, M; Loisel, J C; Jacob, B; Feuilly, C; Stanescu, V

    1991-06-01

    Lethal osteogenesis imperfecta was diagnosed at 27 weeks amenorrea in one fetus of a bichorial twin pregnancy. Sonographic findings included: short-limb dwarfism, hypotrophy and hypoechoic bones. The affected fetus was so translucent that only the normal fetus could be seen on plain in utero radiography. The affected fetus died immediately after birth. Postmortem radiography and histology were typical of lethal osteogenesis imperfecta of type IIA. Aids to the etiological diagnosis of in utero dwarfism are presented. Sonographic features correlated with neonatal death are described.

  7. Prevention of neuromusculoskeletal frailty in slow-aging ames dwarf mice: longitudinal investigation of interaction of longevity genes and caloric restriction.

    Directory of Open Access Journals (Sweden)

    Oge Arum

    Full Text Available Ames dwarf (Prop1 (df/df mice are remarkably long-lived and exhibit many characteristics of delayed aging and extended healthspan. Caloric restriction (CR has similar effects on healthspan and lifespan, and causes an extension of longevity in Ames dwarf mice. Our study objective was to determine whether Ames dwarfism or CR influence neuromusculoskeletal function in middle-aged (82 ± 12 weeks old or old (128 ± 14 w.o. mice. At the examined ages, strength was improved by dwarfism, CR, and dwarfism plus CR in male mice; balance/ motor coordination was improved by CR in old animals and in middle-aged females; and agility/ motor coordination was improved by a combination of dwarfism and CR in both genders of middle-aged mice and in old females. Therefore, extension of longevity by congenital hypopituitarism is associated with improved maintenance of the examined measures of strength, agility, and motor coordination, key elements of frailty during human aging, into advanced age. This study serves as a particularly important example of knowledge related to addressing aging-associated diseases and disorders that results from studies in long-lived mammals.

  8. The Enigma behind Pituitary and Sella Turcica

    Directory of Open Access Journals (Sweden)

    Umarevathi Gopalakrishnan

    2015-01-01

    Full Text Available The pituitary gland’s role as a functional matrix for sella turcica has not been suggested in orthodontic literature. This paper is an attempt to correlate the role of pituitary gland in the development of sella turcica. A case report of dwarfism associated with hypopituitarism is presented to highlight the above hypothesis.

  9. A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome.

    NARCIS (Netherlands)

    Meetei, AR; Sechi, S; Wallisch, M; Yang, D; Young, MK; Joenje, H.; Hoatlin, M.E.

    2003-01-01

    Bloom syndrome (BS) is a genetic disorder associated with dwarfism, immunodeficiency, reduced fertility, and an elevated risk of cancer. To investigate the mechanism of this disease, we isolated from human HeLa extracts three complexes containing the helicase defective in BS, BLM. Interestingly, one

  10. Cockayne′s syndrome

    Directory of Open Access Journals (Sweden)

    Krishna K

    1995-01-01

    Full Text Available A 10-year old boy, a product of consanguineous marriage was diagnosed clinically as a case of Cockayne′s syndrome because of delayed milestones, deaf mutism with spastic paraplegia, dwarfism, salt and pepper fundus, typical facies and a photosensitive rash on the butterfly area of the face

  11. Sleep and upper airway obstruction in children with achondroplasia

    NARCIS (Netherlands)

    Zucconi, M; Weber, G; Castronovo, [No Value; FeriniStrambi, L; Russo, F; Chiumello, G; Smirne, S

    1996-01-01

    Objective: The features of achondroplasia, the most common form of dwarfism, includes short cranial base and midface hypoplasia; both abnormalities increased the risk of upper airway obstruction during sleep, The aim of our study was to evaluate sleep and respiratory function of children with achond

  12. FGFR4 Downregulation of Cell Adhesion in Prostate Cancer

    Science.gov (United States)

    2008-09-01

    in Figure 1, all constructs were stably incorporated into 293-RXR cells and were inducible upon treatment with Ponasterone A. Though we had created...through the transmembrane domain, similar to the FGFR3 Gly380Arg mutation responsible for human dwarfism, or achondroplasia . In this model, the FGFR4

  13. Rud′s syndrome

    Directory of Open Access Journals (Sweden)

    K Pavani

    2014-01-01

    Full Text Available Rud′s syndrome is a rare autosomal recessive hereditary disorder characterized by congenital ichthyosis, epilepsy, dwarfism, sexual infantilism, polyneuritis, and macrocytic anemia. We report here an interesting case of this disorder in an 18-year-old girl for its rarity and academic interest.

  14. Achondroplasia: Craniofacial manifestations and considerations in dental management

    OpenAIRE

    Al-Saleem,Afnan; Al-Jobair, Asma

    2010-01-01

    Achondroplasia is the most common form of skeletal dysplasia dwarfism that manifests with stunted stature and disproportionate limb shortening. Achondroplasia is of dental interest because of its characteristic craniofacial features which include relative macrocephaly, depressed nasal bridge and maxillary hypoplasia. Presence of large head, implanted shunt, airway obstruction and difficulty in head control require special precautions during dental management. Craniofacial manifestations and c...

  15. Establishment of a novel dwarf rat strain: cartilage calcification insufficient (CCI) rats.

    Science.gov (United States)

    Tanaka, Masami; Watanabe, Minoru; Yokomi, Izuru; Matsumoto, Naoki; Sudo, Katsuko; Satoh, Hitoshi; Igarashi, Tsuneo; Seki, Azusa; Amano, Hitoshi; Ohura, Kiyoshi; Ryu, Kakei; Shibata, Shunichi; Nagayama, Motohiko; Tanuma, Jun-ichi

    2015-01-01

    Rats with dwarfism accompanied by skeletal abnormalities, such as shortness of the limbs, tail, and body (dwarf rats), emerged in a Jcl-derived Sprague-Dawley rat colony maintained at the Institute for Animal Experimentation, St. Marianna University Graduate School of Medicine. Since the dwarfism was assumed to be due to a genetic mutation based on its frequency, we bred the dwarf rats and investigated their characteristics in order to identify the causative factors of their phenotypes and whether they could be used as a human disease model. One male and female that produced dwarf progeny were selected, and reproduction was initiated by mating the pair. The incidence of dwarfism was 25.8% among the resultant litter, and dwarfism occurred in both genders, suggesting that it was inherited in an autosomal recessive manner. At 12 weeks of age, the body weights of the male and female dwarf rats were 40% and 57% of those of the normal rats, respectively. In soft X-ray radiographic and histological examinations, shortening and hypoplasia of the long bones, such as the tibia and femur, were observed, which were suggestive of endochondral ossification abnormalities. An immunohistochemical examination detected an aggrecan synthesis disorder, which might have led to delayed calcification and increased growth plate thickening in the dwarf rats. We hypothesized that the principal characteristics of the dwarf rats were systemically induced by insufficient cartilage calcification in their long bones; thus, we named them cartilage calcification insufficient (CCI) rats.

  16. Pseudoachondroplasia: A case report

    Directory of Open Access Journals (Sweden)

    Radlović Vladimir

    2013-01-01

    Full Text Available Introduction. Pseudoachondroplasia (PSACH is an autosomal dominant osteochondrodysplasia due to mutations in the gene encoding cartilage oligomeric matrix protein. It is characterized by rhizomelic dwarfism, limb and vertebral deformity, joint laxity and early onset osteoarthrosis. We present the girl with the early expressed and severe PSACH born to clinically and radiographically unaffected parents. Case Outline. A 6.5-year-old girl presented with short-limbed dwarfism (body height 79.5 cm, dwarfism became increasingly visible, and since completed 15 months of age, when she started to walk, the disease was complicated with genu varum, lumbar lordosis and abnormal gait. Beside visibly short forearms, short, broad and ulnar deviation of the hands, brachydactyly and joint hyperlaxity, the radiographic picture showed markedly flared metaphyses, small and irregular epiphyses and poorly formed acetabulum. Conclusion. PSACH is an achondroplasia-like rhizomelic dwarfism recognized by the absence of abnormality at birth, normal craniofacial appearance, characteristic epiphyseal and metaphyseal radiographic finding and joint hyperlaxity.

  17. Dental Management of a 14-Year-Old with Cockayne Syndrome under General Anesthesia

    Directory of Open Access Journals (Sweden)

    Divya Gaddam

    2014-01-01

    Full Text Available Cockayne’s syndrome is a rare, autosomal recessive disorder characterized clinically by cachectic dwarfism, cutaneous photosensitivity, loss of adipose tissue, mental retardation, skeletal and neurological abnormalities, and pigmentary degeneration of the retina. Dental caries is a common finding. Dental rehabilitation of a 14-year-old male with Cockayne’s syndrome is presented.

  18. Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of meier-gorlin syndrome

    NARCIS (Netherlands)

    Stiff, T.; Alagoz, M.; Alcantara, D.; Outwin, E.; Brunner, H.G.; Bongers, M.H.F.; O'Driscoll, M.; Jeggo, P.A.

    2013-01-01

    Mutations in ORC1, ORC4, ORC6, CDT1, and CDC6, which encode proteins required for DNA replication origin licensing, cause Meier-Gorlin syndrome (MGS), a disorder conferring microcephaly, primordial dwarfism, underdeveloped ears, and skeletal abnormalities. Mutations in ATR, which also functions duri

  19. Mutations in the pre-replication complex cause Meier-Gorlin syndrome

    NARCIS (Netherlands)

    Bicknell, L.S.; Bongers, M.H.F.; Leitch, A.; Brown, S.; Schoots, J.; Harley, M.E.; Aftimos, S.; Al-Aama, J.Y.; Bober, M.; Brown, P.A.; Bokhoven, J.H.L.M. van; Dean, J.; Edrees, A.Y.; Feingold, M.; Fryer, A.; Hoefsloot, L.H.; Kau, N.; Knoers, N.V.A.M.; Mackenzie, J.; Opitz, J.M.; Sarda, P.; Ross, A.; Temple, I.K.; Toutain, A.; Wise, C.A.; Wright, M.; Jackson, A.P.

    2011-01-01

    Meier-Gorlin syndrome (ear, patella and short-stature syndrome) is an autosomal recessive primordial dwarfism syndrome characterized by absent or hypoplastic patellae and markedly small ears(1)(3). Both pre- and post-natal growth are impaired in this disorder, and although microcephaly is often evid

  20. Molecular genetic studies in Fragaria species: Agrobacterium-mediated transformation and fine mapping of the Phytophthora fragariae resistance gene Rpf1.

    NARCIS (Netherlands)

    Haymes, K.M.

    1997-01-01

    The fungus Phytophthora fragariae, is able to cause red stele root rot in the strawberry. Symptoms of the disease is discolouration of the stele of the roots, rotting away of the infected roots, dwarfism, wilting, and finally plant death. Chemical control of red stele with soil fumigants reduce the

  1. New syndrome with ocular, skeletal and renal involvement

    Energy Technology Data Exchange (ETDEWEB)

    Cirillo Silengo, M.; Lopez Bell, G.; Biagioli, M.; Guala, A.; Franceschini, P.; Porcellini, G.

    1987-03-01

    A patient with retinitis pigmentosa, hypertension with interstitial nephropathy, short limb dwarfism with Madelung deformity of the forearms and an unclassified type of brachydactyly is described. Such bone dysplasia has never been reported to date either as a single entity or associated with renal and retinal diseases.

  2. Case report of Ellis-Van Creveld syndrome

    Directory of Open Access Journals (Sweden)

    Baghdadi T

    2001-09-01

    Full Text Available Ellis-van Creveld sydrome (Chondroectodermal dysplasia is a hereditary form of short limb disproportionate dwarfism characterized by diffuse involvement of skeletal system and visceral organs. Two brothers affected by this syndrome are presented here following a brief account of the disease's manifestations.

  3. The transcriptional repressor Zbtb20 is essential for specification of hippocampal projection neurons and territory in mice

    DEFF Research Database (Denmark)

    Rosenthal, Eva Helga

    for specification of both hippocampal pyramidal neurons and territory in a mouse knockout model. Homozygous Zbtb20-/- mice are viable at birth, but display dwarfism and die during the first month of postnatal life. Characterization of the Zbtb20-/- brain phenotype reveals a small vestigial hippocampus...

  4. MRI Findings of Coexistence of Ectopic Neurohypophysis, Corpus Callosum Dysgenesis, and Periventricular Neuronal Heterotopia

    Directory of Open Access Journals (Sweden)

    Harun Arslan

    2014-01-01

    Full Text Available Ectopic neurohypophysis is a pituitary gland abnormality, which can accompany growth hormone deficiency associated with dwarfism. Here we present magnetic resonance imaging (MRI findings of a rare case of ectopic neurohypophysis, corpus callosum dysgenesis, and periventricular neuronal heterotopia coexisting, with a review of the literature.

  5. The transcriptional repressor Zbtb20 is essential for specification of hippocampal projection neurons and territory in mice

    DEFF Research Database (Denmark)

    Rosenthal, Eva Helga

    for specification of both hippocampal pyramidal neurons and territory in a mouse knockout model. Homozygous Zbtb20-/- mice are viable at birth, but display dwarfism and die during the first month of postnatal life. Characterization of the Zbtb20-/- brain phenotype reveals a small vestigial hippocampus...... as an essential regulator of various aspects of neuronal development and corticogenesis in the hippocampus....

  6. A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome.

    NARCIS (Netherlands)

    Meetei, AR; Sechi, S; Wallisch, M; Yang, D; Young, MK; Joenje, H.; Hoatlin, M.E.

    2003-01-01

    Bloom syndrome (BS) is a genetic disorder associated with dwarfism, immunodeficiency, reduced fertility, and an elevated risk of cancer. To investigate the mechanism of this disease, we isolated from human HeLa extracts three complexes containing the helicase defective in BS, BLM. Interestingly, one

  7. The Enigma behind Pituitary and Sella Turcica.

    Science.gov (United States)

    Gopalakrishnan, Umarevathi; Mahendra, Lodd; Rangarajan, Sumanth; Madasamy, Ramasamy; Ibrahim, Mohammad

    2015-01-01

    The pituitary gland's role as a functional matrix for sella turcica has not been suggested in orthodontic literature. This paper is an attempt to correlate the role of pituitary gland in the development of sella turcica. A case report of dwarfism associated with hypopituitarism is presented to highlight the above hypothesis.

  8. The Enigma behind Pituitary and Sella Turcica

    OpenAIRE

    Umarevathi Gopalakrishnan; Lodd Mahendra; Sumanth Rangarajan; Ramasamy Madasamy; Mohammad Ibrahim

    2015-01-01

    The pituitary gland’s role as a functional matrix for sella turcica has not been suggested in orthodontic literature. This paper is an attempt to correlate the role of pituitary gland in the development of sella turcica. A case report of dwarfism associated with hypopituitarism is presented to highlight the above hypothesis.

  9. Novel growth hormone receptor gene mutation in a patient with Laron syndrome.

    Science.gov (United States)

    Arman, Ahmet; Yüksel, Bilgin; Coker, Ajda; Sarioz, Ozlem; Temiz, Fatih; Topaloglu, Ali Kemal

    2010-04-01

    Growth Hormone (GH) is a 22 kDa protein that has effects on growth and glucose and fat metabolisms. These effects are initiated by binding of growth hormone (GH) to growth hormone receptors (GHR) expressed in target cells. Mutations or deletions in the growth hormone receptor cause an autosomal disorder called Laron-type dwarfism (LS) characterized by high circulating levels of serum GH and low levels of insulin like growth factor-1 (IGF-1). We analyzed the GHR gene for genetic defect in seven patients identified as Laron type dwarfism. We identified two missense mutations (S40L and W104R), and four polymorphisms (S473S, L526I, G168G and exon 3 deletion). We are reporting a mutation (W104R) at exon 5 of GHR gene that is not previously reported, and it is a novel mutation.

  10. Perceval S aortic valve implantation in an achondroplastic Dwarf

    Directory of Open Access Journals (Sweden)

    Nikolaos G Baikoussis

    2016-01-01

    Full Text Available Despite cardiovascular disease in patients with dwarfism is not rare; there is a lack of reports referring to cardiac interventions in such patients. Dwarfism may be due to achondroplasia or hormonal growth disorders. We present a 58-year-old woman with episodes of dyspnea for several months. She underwent on transthoracic echocardiography, and she diagnosed with severe aortic valve stenosis. She referred to our department for surgical treatment of this finding. In accordance of her anthropometric characteristics and her very small aortic annulus, we had the dilemma of prosthesis selection. We decided to implant a stentless valve to optimize her effective orifice area. Our aim is to present the successful Perceval S valve implantation and the descriptions of the problems coming across in operating on these special patients. To our knowledge, this is the first case patient in which a Perceval S valve is implanted according to the international bibliography.

  11. Response of luteinizing hormone and follicle stimulating hormone to luteinizing hormone-releasing hormone in prepubertal and pubertal chidren, as measured by a highly sensitive immunradiometric assay

    OpenAIRE

    樋口,譲二

    1992-01-01

    To investigate the age-related changes in the pituitary responsiveness to luteinizing hormone-releasing hormone (LH-RH), the consentrations of serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured before and after LH-RH administra-tion using the highly sensitive immunoradiometric assay (IRMA) in 283 normal children (161 males and 77 females) between 4 and 14 years old and in 22 patients (18 males and 4 females) with pituitary dwarfism. Then, the area of response ...

  12. Fibrochondrogenesis, an Antenatal and Postnatal Correlation

    Directory of Open Access Journals (Sweden)

    Nischal G Kundaragi

    2012-01-01

    Full Text Available Fibrochondrogenesis is a rare, neonatally lethal osteochondrodysplasia, with autosomal recessive inheritance. It differs from other lethal dwarfisms in that it leads to broad, long-bone metaphyses (dumb-bell shaped and pear-shaped vertebral bodies. We report a case of fibrochondrogenesis with severe pear-shaped platyspondyly, suspected antenatally, and give a comprehensive pictorial review of the antenatal ultrasound and postnatal radiographic findings. Only few cases of fibrochondrogenesis are diagnosed before the termination of pregnancy.

  13. MRI Findings in Spinal Canal Stenosis

    OpenAIRE

    Maryam Barzin

    2010-01-01

    Spinal canal stenosis results from progressive narrowing of the central spinal canal and the lateral recesses. Primary (congenital) lumbar spinal stenosis is associated with achondroplastic dwarfism. The spinal canal may become narrowed by bulging or protrusion of the intervertebral disc annulus, herniation of the nucleus pulposus posteriorly, thickening of the posterior longitudinal ligament, hypertrophy of the facet joints, hypertrophy of the ligamentum flavum, epidural fat deposition, spon...

  14. Murk Jansen's metaphyseal chondrodysplasia with long-term follow-up

    Energy Technology Data Exchange (ETDEWEB)

    Silverthorn, K.G.; Houston, C.S.; Duncan, B.P.

    1987-02-01

    The fourteenth reported patient with Murk Jansen's metaphyseal chondrodysplasia is presented, with a remarkable followup from birth to the age of 15 years. Numerous invasive procedures were performed in pursuit of erroneous provisional diagnoses. Five of these patients presented in infancy with radiographic metaphyseal changes similar to rickets, but with preservation of the provisional zone of calcification. Following infancy, these patients reveal the more typical short-limbed dwarfism, with fusiform joints and bowed extremities.

  15. Four new bat species (Rhinolophus hildebrandtii complex reflect Plio-Pleistocene divergence of dwarfs and giants across an Afromontane archipelago.

    Directory of Open Access Journals (Sweden)

    Peter J Taylor

    Full Text Available Gigantism and dwarfism evolve in vertebrates restricted to islands. We describe four new species in the Rhinolophus hildebrandtii species-complex of horseshoe bats, whose evolution has entailed adaptive shifts in body size. We postulate that vicissitudes of palaeoenvironments resulted in gigantism and dwarfism in habitat islands fragmented across eastern and southern Africa. Mitochondrial and nuclear DNA sequences recovered two clades of R. hildebrandtii senso lato which are paraphyletic with respect to a third lineage (R. eloquens. Lineages differ by 7.7 to 9.0% in cytochrome b sequences. Clade 1 includes R. hildebrandtii sensu stricto from the east African highlands and three additional vicariants that speciated across an Afromontane archipelago through the Plio-Pleistocene, extending from the Kenyan Highlands through the Eastern Arc, northern Mozambique and the Zambezi Escarpment to the eastern Great Escarpment of South Africa. Clade 2 comprises one species confined to lowland savanna habitats (Mozambique and Zimbabwe. A third clade comprises R. eloquens from East Africa. Speciation within Clade 1 is associated with fixed differences in echolocation call frequency, and cranial shape and size in populations isolated since the late Pliocene (ca 3.74 Mya. Relative to the intermediate-sized savanna population (Clade 2, these island-populations within Clade 1 are characterised by either gigantism (South African eastern Great Escarpment and Mts Mabu and Inago in Mozambique or dwarfism (Lutope-Ngolangola Gorge, Zimbabwe and Soutpansberg Mountains, South Africa. Sympatry between divergent clades (Clade 1 and Clade 2 at Lutope-Ngolangola Gorge (NW Zimbabwe is attributed to recent range expansions. We propose an "Allometric Speciation Hypothesis", which attributes the evolution of this species complex of bats to divergence in constant frequency (CF sonar calls. The origin of species-specific peak frequencies (overall range = 32 to 46 kHz represents the

  16. Septo-optic dysplasia, subglottic stenosis and skeletal abnormalities: a case report.

    Science.gov (United States)

    Wakeling, Emma L; Dattani, Mehul T; Bloch-Zupan, A; Winter, Robin M; Holder, Susan E

    2003-04-01

    We report a girl with septo-optic dysplasia in association with subglottic stenosis, sagittal craniosynostosis, osteoporosis and dental anomalies. It is uncommon for patients with septo-optic dysplasia to have multiple, extra-cranial malformations. A number of differential diagnoses were considered in this case, including Cole-Carpenter syndrome, Pfeiffer syndrome and osteoglophonic dwarfism. However, none can account for all the abnormalities seen. We therefore believe that this is a previously unreported, but highly distinctive, phenotype.

  17. Uzu mutation in barley (Hordeum vulgare L.) reduces the leaf unrolling response to brassinolide.

    Science.gov (United States)

    Honda, Ichiro; Zeniya, Haruko; Yoneyama, Koichi; Chono, Makiko; Kaneko, Shigenobu; Watanabe, Yoshiaki

    2003-05-01

    A sensitive method to examine the brassinolide (BL) response of barley (Hordeum vulgare L.) using dark-grown leaf segments was established based on the known method for wheat. BL responses of 53 dwarf isogenic lines of barley were examined, and two lines were found having a uzu gene that doesn't respond significantly. These results indicate that uzu dwarfism may be caused by the non-responding character to BL.

  18. Progeria syndrome: A case report

    Directory of Open Access Journals (Sweden)

    Rastogi Rajul

    2008-01-01

    Full Text Available Progeria is a rare and peculiar combination of dwarfism and premature aging. The incidence is one in several million births. It occurs sporadically and is probably an autosomal recessive syndrome. Though the clinical presentation is usually typical, conventional radiological and biochemical investigations help in confirming the diagnosis. We present a rare case of progeria with most of the radiological features as a pictorial essay.

  19. A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse)

    OpenAIRE

    Zhou, Yihua; Xu, Bixiong C.; Maheshwari, Hiralal G.; He, Li; Reed, Michael; Lozykowski, Maria; Okada, Shigeru; Cataldo, Lori; Coschigamo, Karen; Wagner, Thomas E.; Baumann, Gerhard; Kopchick, John J.

    1997-01-01

    Laron syndrome [growth hormone (GH) insensitivity syndrome] is a hereditary dwarfism resulting from defects in the GH receptor (GHR) gene. GHR deficiency has not been reported in mammals other than humans. Many aspects of GHR dysfunction remain unknown because of ethical and practical limitations in studying humans. To create a mammalian model for this disease, we generated mice bearing a disrupted GHR/binding protein (GHR/BP) gene through a homologous gene targeting approach. Homozygous GHR/...

  20. Fixator-Assisted Lengthening and Deformity Correction Over an Intramedullary Nail in a Patient with Achondroplasia

    OpenAIRE

    Erdal Uzun

    2016-01-01

    Achondroplasia is the most frequently encountered form of nonlethal skeletal dysplasia and a type of rhizomelic dwarfism. It results in considerable physical and psychologic handicaps owing to the disproportionate stature of the body and difficulty in performing routine activities of daily living. They also have major musculoskeletal problems including symptomatic malalignment of the lower limbs. Limb lengthening has been used in patients with achondroplasia by different techniques (Intramed...

  1. Effects of diadenosine tetraphosphate on FGF9-induced chloride flux changes in achondroplastic chondrocytes

    OpenAIRE

    Huete, Fernando; Guzman-Aranguez, Ana; Ortín, Javier; Hoyle, Charles H. V.; Pintor, Jesús

    2011-01-01

    Achondroplasia, the most common type of dwarfism, is characterized by a mutation in the fibroblast growth factor receptor 3 (FGFR3). Achondroplasia is an orphan pathology with no pharmacological treatment so far. However, the possibility of using the dinucleotide diadenosine tetraphosphate (Ap4A) with therapeutic purposes in achondroplasia has been previously suggested. The pathogenesis involves the constitutive activation of FGFR3, resulting in altered biochemical and physiological processes...

  2. Genetic inactivation of ERK1 and ERK2 in chondrocytes promotes bone growth and enlarges the spinal canal

    OpenAIRE

    Sebastian, Arjun; Matsushita, Takehiko; Kawanami, Aya; Mackem, Susan; Landreth, Gary; Murakami, Shunichi

    2010-01-01

    Activating mutations in FGFR3 cause the most common forms of human dwarfism: achondroplasia and thanatophoric dysplasia. In mouse models of achondroplasia, recent studies have implicated the ERK MAPK pathway, a pathway activated by FGFR3, in creating reduced bone growth. Our recent studies have indicated that increased Fgfr3 and ERK MAPK signaling in chondrocytes also causes premature synchondrosis closure in the cranial base and vertebrae, accounting for the sometimes fatal stenosis of the f...

  3. Orofacial manifestations of achondroplasia

    OpenAIRE

    Kaushik, Atul; Kumar, Munish; Rohilla, Smriti; Tanwar, Renu; V C Vinod

    2012-01-01

    Achondroplasia (Online Mendelian Inheritance in Man [OMIM] 100800), is considered as a form of skeletal dysplasia dwarfism that manifests with stunted stature and disproportionate limb shortening. Achondroplasia is of special interest in the field of dentistry because of its characteristic craniofacial features which include relative macrocephaly, depressed nasal bridge and maxillary hypoplasia. Presence of large head, implanted shunt, airway obstruction and difficulty in head control require...

  4. Murk Jansen's metaphyseal chondrodysplasia with long-term followup.

    Science.gov (United States)

    Silverthorn, K G; Houston, C S; Duncan, B P

    1987-01-01

    The fourteenth reported patient with Murk Jansen's metaphyseal chondrodysplasia is presented, with a remarkable followup from birth to the age of 15 years. Numerous invasive procedures were performed in pursuit of erroneous provisional diagnoses. Five of these patients presented in infancy with radiographic metaphyseal changes similar to rickets, but with preservation of the provisional zone of calcification. Following infancy, these patients reveal the more typical short-limbed dwarfism, with fusiform joints and bowed extremities.

  5. Distinctive skeletal dysplasia in Cockayne syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Silengo, M.C.; Franceschini, P.; Bianco, R.; Biagioli, M.; Pastorin, L.; Vista, N.; Baldassar, A.; Benso, L.

    1986-03-01

    Cockayne syndrome is a well-known autosomal recessive form of dwarfism with senile-like appearance. Skeletal changes such as flattening of vertebral bodies, ivory epiphyses and thickening of cranial vault, have been observed in some patients with this condition. We describe here a 5.5-year-old girl with the typical clinical signs of Cockayne syndrome and a distinctive form of bone dysplasia with major involvement of the spine.

  6. [Psychosocial intellectual development of children with infantile cystinosis and cerebral atrophy (author's transl)].

    Science.gov (United States)

    Ehrich, J H; Wolff, G; Stoeppler, L; Heyer, R; Offner, G; Brodehl, J

    1979-09-01

    The psychosocial and intellectual development of 4 boys with nephropathic cystinosis and brain atrophy documented by cranial computerized tomography was investigated by use of biographical data and psychological tests (HAWIK, Deutscher Rechtschreibtest). Inspite of the brain atrophy the patients showed low-normal intellectual capacities and mainly average school performance. There were no psychosocial abnormalities correlated to the primary metabolic disease. However, renal dwarfism led to mascotism requiring psychotherapy.

  7. Grebe syndrome with bilateral fibular hemimelia and thumb duplication

    Energy Technology Data Exchange (ETDEWEB)

    Rao, Narasimha; Joseph, Benjamin [Department of Orthopaedics, Kasturba Medical College, Karnataka State (India)

    2002-03-01

    Grebe syndrome is a rare recessively inherited form of short-limbed dwarfism. Among the skeletal anomalies reported in the past, complete fibular hemimelia and thumb duplication have not been documented. We report a case of Grebe syndrome with these associated anomalies and review the various skeletal anomalies reported in the literature related to this syndrome. Awareness of the skeletal anomalies that can occur in this syndrome should enable an accurate diagnosis. (orig.)

  8. Disruption of mouse Cenpj, a regulator of centriole biogenesis, phenocopies Seckel syndrome.

    Directory of Open Access Journals (Sweden)

    Rebecca E McIntyre

    Full Text Available Disruption of the centromere protein J gene, CENPJ (CPAP, MCPH6, SCKL4, which is a highly conserved and ubiquitiously expressed centrosomal protein, has been associated with primary microcephaly and the microcephalic primordial dwarfism disorder Seckel syndrome. The mechanism by which disruption of CENPJ causes the proportionate, primordial growth failure that is characteristic of Seckel syndrome is unknown. By generating a hypomorphic allele of Cenpj, we have developed a mouse (Cenpj(tm/tm that recapitulates many of the clinical features of Seckel syndrome, including intrauterine dwarfism, microcephaly with memory impairment, ossification defects, and ocular and skeletal abnormalities, thus providing clear confirmation that specific mutations of CENPJ can cause Seckel syndrome. Immunohistochemistry revealed increased levels of DNA damage and apoptosis throughout Cenpj(tm/tm embryos and adult mice showed an elevated frequency of micronucleus induction, suggesting that Cenpj-deficiency results in genomic instability. Notably, however, genomic instability was not the result of defective ATR-dependent DNA damage signaling, as is the case for the majority of genes associated with Seckel syndrome. Instead, Cenpj(tm/tm embryonic fibroblasts exhibited irregular centriole and centrosome numbers and mono- and multipolar spindles, and many were near-tetraploid with numerical and structural chromosomal abnormalities when compared to passage-matched wild-type cells. Increased cell death due to mitotic failure during embryonic development is likely to contribute to the proportionate dwarfism that is associated with CENPJ-Seckel syndrome.

  9. Disruption of mouse Cenpj, a regulator of centriole biogenesis, phenocopies Seckel syndrome.

    Directory of Open Access Journals (Sweden)

    Rebecca E McIntyre

    Full Text Available Disruption of the centromere protein J gene, CENPJ (CPAP, MCPH6, SCKL4, which is a highly conserved and ubiquitiously expressed centrosomal protein, has been associated with primary microcephaly and the microcephalic primordial dwarfism disorder Seckel syndrome. The mechanism by which disruption of CENPJ causes the proportionate, primordial growth failure that is characteristic of Seckel syndrome is unknown. By generating a hypomorphic allele of Cenpj, we have developed a mouse (Cenpj(tm/tm that recapitulates many of the clinical features of Seckel syndrome, including intrauterine dwarfism, microcephaly with memory impairment, ossification defects, and ocular and skeletal abnormalities, thus providing clear confirmation that specific mutations of CENPJ can cause Seckel syndrome. Immunohistochemistry revealed increased levels of DNA damage and apoptosis throughout Cenpj(tm/tm embryos and adult mice showed an elevated frequency of micronucleus induction, suggesting that Cenpj-deficiency results in genomic instability. Notably, however, genomic instability was not the result of defective ATR-dependent DNA damage signaling, as is the case for the majority of genes associated with Seckel syndrome. Instead, Cenpj(tm/tm embryonic fibroblasts exhibited irregular centriole and centrosome numbers and mono- and multipolar spindles, and many were near-tetraploid with numerical and structural chromosomal abnormalities when compared to passage-matched wild-type cells. Increased cell death due to mitotic failure during embryonic development is likely to contribute to the proportionate dwarfism that is associated with CENPJ-Seckel syndrome.

  10. Small scattered fragments do not a dwarf make: biological and archaeological data indicate that prehistoric inhabitants of Palau were normal sized.

    Directory of Open Access Journals (Sweden)

    Scott M Fitzpatrick

    Full Text Available UNLABELLED: Current archaeological evidence from Palau in western Micronesia indicates that the archipelago was settled around 3000-3300 BP by normal sized populations; contrary to recent claims, they did not succumb to insular dwarfism. BACKGROUND: Previous and ongoing archaeological research of both human burial and occupation sites throughout the Palauan archipelago during the last 50 years has produced a robust data set to test hypotheses regarding initial colonization and subsequent adaptations over the past three millennia. PRINCIPAL FINDINGS: Close examination of human burials at the early (ca. 3000 BP and stratified site of Chelechol ra Orrak indicates that these were normal sized individuals. This is contrary to the recent claim of contemporaneous "small-bodied" individuals found at two cave sites by Berger et al. (2008. As we argue, their analyses are flawed on a number of different analytical levels. First, their sample size is too small and fragmentary to adequately address the variation inherent in modern humans within and outside of Palau. Second, the size and stature of all other prehistoric (both older and contemporaneous skeletal assemblages found in Palau fall within the normal parameters of modern human variation in the region, indicating this was not a case of insular dwarfism or a separate migratory group. Third, measurements taken on several skeletal elements by Berger et al. may appear to be from smaller-bodied individuals, but the sizes of these people compares well with samples from Chelechol ra Orrak. Last, archaeological, linguistic, and historical evidence demonstrates a great deal of cultural continuity in Palau through time as expected if the same population was inhabiting the archipelago. CONCLUSIONS: Prehistoric Palauan populations were normal sized and exhibit traits that fall within the normal variation for Homo sapiens-they do not support the claims by Berger et al. (2008 that there were smaller

  11. The leukemia-associated Rho guanine nucleotide exchange factor LARG is required for efficient replication stress signaling.

    Science.gov (United States)

    Beveridge, Ryan D; Staples, Christopher J; Patil, Abhijit A; Myers, Katie N; Maslen, Sarah; Skehel, J Mark; Boulton, Simon J; Collis, Spencer J

    2014-01-01

    We previously identified and characterized TELO2 as a human protein that facilitates efficient DNA damage response (DDR) signaling. A subsequent yeast 2-hybrid screen identified LARG; Leukemia-Associated Rho Guanine Nucleotide Exchange Factor (also known as Arhgef12), as a potential novel TELO2 interactor. LARG was previously shown to interact with Pericentrin (PCNT), which, like TELO2, is required for efficient replication stress signaling. Here we confirm interactions between LARG, TELO2 and PCNT and show that a sub-set of LARG co-localizes with PCNT at the centrosome. LARG-deficient cells exhibit replication stress signaling defects as evidenced by; supernumerary centrosomes, reduced replication stress-induced γH2AX and RPA nuclear foci formation, and reduced activation of the replication stress signaling effector kinase Chk1 in response to hydroxyurea. As such, LARG-deficient cells are sensitive to replication stress-inducing agents such as hydroxyurea and mitomycin C. Conversely we also show that depletion of TELO2 and the replication stress signaling kinase ATR leads to RhoA signaling defects. These data therefore reveal a level of crosstalk between the RhoA and DDR signaling pathways. Given that mutations in both ATR and PCNT can give rise to the related primordial dwarfism disorders of Seckel Syndrome and Microcephalic osteodysplastic primordial dwarfism type II (MOPDII) respectively, which both exhibit defects in ATR-dependent checkpoint signaling, these data also raise the possibility that mutations in LARG or disruption to RhoA signaling may be contributory factors to the etiology of a sub-set of primordial dwarfism disorders.

  12. Spondyloepiphseal dysplasia congenita in siblings born to unaffected parents: ? germ line mosaicism

    Energy Technology Data Exchange (ETDEWEB)

    Mulla, W.; McDonald-McGinn, D.; Zackai, E. [Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)] [and others

    1994-09-01

    Germ line mosaicism has been used to explain the birth of more than one child affected with a dominantly inherited disorder born to unaffected parents. Furthermore, it has been confirmed clinically in families where recurrence in siblings was originally thought to be autosomal recessive, but were affected individuals have reproduced affected offspring. Firm evidence of germ line mosaicism using mutation analysis by molecular methods exists for some autosomal disorders. We present two siblings with spondyloepipheseal dysplasia congenita (SEDC) born to unaffected parents. This suggests the presence of germ line mosaicism in this entity. Patient 1 was born at 32 weeks gestation to a G1P1 Puerto Rican mother. The pregnancy was complicated by polyhydramnios. The neonate, a short-limbed dwarf, died at 15 hours of age from respiratory distress and a compromised thoracic cavity. Patient 2, the sibling of patient 1 was born at 37 weeks gestation after a pregnancy complicated by polyhydramnios and prenatal ultrasound diagnosis of short-limbed dwarfism. The diagnosis of SEDC was made and, after review of the sibling`s postmortem X-rays, it was felt that she was similarly affected. The family history reveals no history of dwarfism or consanguinity. The SEDC is described as an autosomal dominant form of dwarfism with variable presentation including some cases that have been lethal in the neonatal period. SEDC is now believed to represent a family of collagen II mutations. Sporadic cases that have arisen in families with no history have been ascribed to new heterozygous mutations. Other families in which SEDC and SEMD recurred without a family history most likely represent germ line mosaicism. In these cases molecular studies should be pursued to document a collagen II mutation. We believe that germ line mosaicism is the most plausible explanation for recurrence in our family.

  13. Hydrops associated with chondrodysplasia of the fetus in a miniature Scottish Highland cow.

    Science.gov (United States)

    Catalina Cabrera, L; McNabb, Bret R; Woods, Sarah E; Cartoceti, Andrew N; Busch, Rosie C

    2016-03-01

    CASE DESCRIPTION A 2-year-old primiparous miniature Scottish Highland cow with an unknown breeding date was evaluated for suspected hydrops. CLINICAL FINDINGS Transabdominal and transrectal ultrasonographic examination identified a large amount of hypoechoic fluid within an enlarged uterus; the fetus could not be identified. Presence of a severely distended uterus and concerns regarding associated health risks to the cow led to the decision to induce labor. Although fluids were expelled, parturition did not progress further over the following 48 hours. Vaginal examination revealed a partially dilated cervix and an abnormally shaped fetus that was too large to pass vaginally. TREATMENT AND OUTCOME Supportive care was provided to the cow, and a stillborn bull calf was delivered by cesarean section. Grossly evident chondrodystrophic dwarfism with hydrocephalus, compatible with so-called bulldog calf malformations, was confirmed by diagnostic imaging and histopathologic evaluation. The cow recovered from surgery uneventfully and was discharged from the hospital the following day. Genetic analysis of DNA from hair roots collected from the sire and dam confirmed both were carriers of an aggrecan-1 gene mutation (bulldog dwarfism1) previously associated with dwarfism and bulldog calf malformations in Dexter cattle. CLINICAL RELEVANCE To our knowledge, this is the first reported case of bulldog calf malformations associated with an aggrecan-1 gene mutation in miniature Scottish Highland cattle, confirming that at least 1 genetic mutation associated with this condition is found in cattle breeds other than Dexter. The findings highlighted the clinical importance of testing for known genetic diseases in breeding cattle, particularly among miniature breeds.

  14. Overexpression of AtDREB1A causes a severe dwarf phenotype by decreasing endogenous gibberellin levels in soybean [Glycine max (L. Merr].

    Directory of Open Access Journals (Sweden)

    Haicui Suo

    Full Text Available Gibberellic acids (GAs are plant hormones that play fundamental roles in plant growth and developmental processes. Previous studies have demonstrated that three key enzymes of GA20ox, GA3ox, and GA2ox are involved in GA biosynthesis. In this study, the Arabidopsis DREB1A gene driven by the CaMV 35S promoter was introduced into soybean plants by Agrobacterium- mediated transformation. The results showed that the transgenic soybean plants exhibited a typical phenotype of GA-deficient mutants, such as severe dwarfism, small and dark-green leaves, and late flowering compared to those of the non-transgenic plants. The dwarfism phenotype was rescued by the application of exogenous GA(3 once a week for three weeks with the concentrations of 144 µM or three times in one week with the concentrations of 60 µM. Quantitative RT-PCR analysis revealed that the transcription levels of the GA synthase genes were higher in the transgenic soybean plants than those in controls, whereas GA-deactivated genes except GmGA2ox4 showed lower levels of expression. The transcript level of GmGA2ox4 encoding the only deactivation enzyme using C(20-GAs as the substrates in soybean was dramatically enhanced in transgenic plants compared to that of wide type. Furthermore, the contents of endogenous bioactive GAs were significantly decreased in transgenic plants than those of wide type. The results suggested that AtDREB1A could cause dwarfism mediated by GA biosynthesis pathway in soybean.

  15. Osteogenesis imperfecta: pathophysiology and treatment.

    Science.gov (United States)

    Hoyer-Kuhn, Heike; Netzer, Christian; Semler, Oliver

    2015-07-01

    Osteogenesis imperfecta is a rare hereditary disease mostly caused by mutations impairing collagen synthesis and modification. Recently recessive forms have been described influencing differentiation and activity of osteoblasts and osteoclasts. Most prominent signs are fractures due to low traumata and deformities of long bones and vertebrae. Additional patients can be affected by dwarfism, scoliosis Dentinogenesis imperfecta, deafness and a blueish discoloration of the sclera. During childhood state of the art medical treatment are i.v. bisphosphonates to increase bone mass and to reduce fracture rate. Surgical interventions are needed to treat fractures, to correct deformities and should always be accompanied by physiotherapeutic and rehabilitative interventions.

  16. Oral manifestations in growth hormone disorders

    Directory of Open Access Journals (Sweden)

    Gaurav Atreja

    2012-01-01

    Full Text Available Growth hormone is of vital importance for normal growth and development. Individuals with growth hormone deficiency develop pituitary dwarfism with disproportionate delayed growth of skull and facial skeleton giving them a small facial appearance for their age. Both hyper and hypopituitarism have a marked effect on development of oro-facial structures including eruption and shedding patterns of teeth, thus giving an opportunity to treating dental professionals to first see the signs and symptoms of these growth disorders and correctly diagnose the serious underlying disease.

  17. COCKAYNE SYNDROME: REPORT OF TWO CASES WITHIN A FAMILY

    Directory of Open Access Journals (Sweden)

    M. Mohammadi

    1999-07-01

    Full Text Available The clinical and phenotypic features of two siblings (a 12 years old girl and her 7 year old brother with Cockayne syndrome are described. The main problems were mild to moderate mental retardation, dwarfism, clumsy gait, photosensitive skin lesions and progeroid (senile like appearance. Brain CT - scans revealed symmetrical, well defined areas of calcification mainly located at lenticular nuclei, in both patients. Vie brainstem auditory responses also showed increased hearing thresholds and absolute wave latencies, that were more prominent in the older sister. The older patient had a healthy twin sister with normal mental function and phenotypic appearance.

  18. Ellis-van Creveld syndrome with unusual oral and dental findings: A rare clinical entity.

    Science.gov (United States)

    Shaik, Sameeulla; Raviraj, Jayam; Dirasantchu, Suresh; Venkata, Suman S

    2016-01-01

    Ellis-van Creveld (EVC) syndrome, a form of skeletal and chondroectodermal dysplasia, is an autosomal recessive disorder characterized by a tetrad of disproportionate dwarfism, postaxial polydactyly, ectodermal dysplasia, and heart defects. In the present article, we hereby present a case of a 13-year-old girl of Indian ethnicity with EVC syndrome with a remarkable number of classical oral and dental features, with unusual findings such as taurodontism and talons cusp. Such dental findings were reported in few cases only. Despite the fact that oral manifestations play an important role in the diagnosis of EVC, only a few detailed reports have been published in the dental literature.

  19. Ellis–van Creveld syndrome with unusual oral and dental findings: A rare clinical entity

    Science.gov (United States)

    Shaik, Sameeulla; Raviraj, Jayam; Dirasantchu, Suresh; Venkata, Suman S.

    2016-01-01

    Ellis–van Creveld (EVC) syndrome, a form of skeletal and chondroectodermal dysplasia, is an autosomal recessive disorder characterized by a tetrad of disproportionate dwarfism, postaxial polydactyly, ectodermal dysplasia, and heart defects. In the present article, we hereby present a case of a 13-year-old girl of Indian ethnicity with EVC syndrome with a remarkable number of classical oral and dental features, with unusual findings such as taurodontism and talons cusp. Such dental findings were reported in few cases only. Despite the fact that oral manifestations play an important role in the diagnosis of EVC, only a few detailed reports have been published in the dental literature. PMID:27076836

  20. Ellis-van Creveld syndrome with unusual oral and dental findings: A rare clinical entity

    Directory of Open Access Journals (Sweden)

    Sameeulla Shaik

    2016-01-01

    Full Text Available Ellis-van Creveld (EVC syndrome, a form of skeletal and chondroectodermal dysplasia, is an autosomal recessive disorder characterized by a tetrad of disproportionate dwarfism, postaxial polydactyly, ectodermal dysplasia, and heart defects. In the present article, we hereby present a case of a 13-year-old girl of Indian ethnicity with EVC syndrome with a remarkable number of classical oral and dental features, with unusual findings such as taurodontism and talons cusp. Such dental findings were reported in few cases only. Despite the fact that oral manifestations play an important role in the diagnosis of EVC, only a few detailed reports have been published in the dental literature.

  1. The smallest of the small.

    Science.gov (United States)

    Hall, Judith G

    2013-10-01

    Microcephalic Osteodysplastic Primordial Dwarfism (MOPD) II has recently been defined as a PCNT gene defect. Historically, it has been a disorder of interest because of the severe intrauterine growth restriction and postnatal short stature. The very shortest/smallest mature human being undoubtedly had this disorder. Maria Zarate lived between 1864 and 1890 and traveled in sideshows to England and all over North America. Her exceeding short stature was well documented in photographs and by a group of physicians in England. She was Mexican and also had an affected brother. A museum, Museo Casa Grande, about her still exists in Cempoala, Mexico.

  2. Proximal realignment surgery for unilateral chronic patella dislocation in Morquio syndrome: a case report.

    Science.gov (United States)

    Baz, Ali Bülent; Akalin, Serdar; Arik, Hasan; Ergün, Ali

    2011-01-01

    Mucopolysaccharidosis IVA (MPS IVA: Morquio A syndrome) is a lysosomal storage disorder caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Patients with MPS IVA appear healthy at birth. Morquio-specific radiographic changes can be observed prior to clinical signs and symptoms. Patients are usually affected by a severe joint degeneration from the 2nd or 3rd decade. Hyperlaxity of the joints is prominent due to the excess of intermediate metabolites. We report a patient with inherited dwarfism, in which a proximal soft tissue realignment procedure was performed to treat chronic patellar dislocation.

  3. Fixator-Assisted Lengthening and Deformity Correction Over an Intramedullary Nail in a Patient with Achondroplasia

    Directory of Open Access Journals (Sweden)

    Erdal Uzun

    2014-12-01

    Full Text Available Achondroplasia is the most frequently encountered form of nonlethal skeletal dysplasia and a type of rhizomelic dwarfism. It results in considerable physical and psychologic handicaps owing to the disproportionate stature of the body and difficulty in performing routine activities of daily living. They also have major musculoskeletal problems including symptomatic malalignment of the lower limbs. Limb lengthening has been used in patients with achondroplasia by different techniques (Intramedullar nailing, monolateral or circular external fixator. We report our treatment of a patient 17 years of age with achondroplasia for bilateral lower limb length discrepancy and bilateral tibial varus deformity.

  4. Seminoma in a Man with Russell-Silver Syndrome Presenting with Testicular Torsion

    Directory of Open Access Journals (Sweden)

    Satoshi Funada

    2016-01-01

    Full Text Available Russell-Silver syndrome (RSS is a type of primordial dwarfism. Only one case of testicular cancer in RSS has been reported, the pathology of which was nonseminoma. Here, we report a case of seminoma in a 36-year-old man who was diagnosed with RSS at birth. The seminoma was diagnosed when the patient presented with testicular torsion. This is the first report of testicular seminoma in an RSS patient in the literature. We also discussed the correlation between seminoma and RSS.

  5. Function analysis of a semi-dwarf sdg in rice with near isogenic lines

    Institute of Scientific and Technical Information of China (English)

    LI Xiaobo; LIANG Guohua; LI Xiazhen; LI Hongchang; XU Jichen; ZHU Lihuang

    2004-01-01

    The physiological phenotype of the rice semi-dwarf mutant,sdg,was characterized in details using a pair of near isogenic .Neither gibberellin*deficient nor gibberellin-insensitive is characteristic of the sdgphenotype.Byanalyzing the secretion of aamylas and the promotion of stem growth caused by eogenous gibberellin(GA),the sdg plant was found to have decreased sensitivity to the GA at the seedling stage. The dwarfism stature of the sdg mutant can be attributed to the shortened internodes. Increase of the cell sults indicate the protein encded by the wild type gene of sdg may be a regulator for cell elogation.

  6. Purification and cultivation of human pituitary growth hormone secreting cells

    Science.gov (United States)

    Hymer, W. C.

    1979-01-01

    Efforts were directed towards maintenance of actively secreting human pituitary growth hormone cells (somatotrophs) in vitro. The production of human growth hormone (hGH) by this means would be of benefit for the treatment of certain human hypopituitary diseases such as dwarfism. One of the primary approaches was the testing of agents which may logically be expected to increase hGH release. The progress towards this goal is summarized. Results from preliminary experiments dealing with electrophoresis of pituitary cell for the purpose of somatotroph separation are described.

  7. Growth Hormone Treatment in Achondroplasia

    OpenAIRE

    Hiroyuki, Tanaka; Department of Pediatrics, Okayama University Graduate School of Medicine and Dentistry

    2003-01-01

    Achondroplasia is the most common short-limb dwarfism. Since the approval of GH treatment for the short stature in achondroplasia in 1997, 444 patients have been registered in the database. The number of new registrations reached a steady state and it may settle between 20 and 40 patients per year. According to the data registered in the database, the effect of GH treatment in achondroplasia was analyzed. The first year of the treatment saw significantly increased annual height gain by 1.4 cm...

  8. Clinics in diagnostic imaging (112). Perinatal lethal hypophosphatasia (PLH).

    Science.gov (United States)

    Kritsaneepaiboon, S; Jaruratanasirikul, S; Dissaneevate, S

    2006-11-01

    A two-hour-old female infant presented with respiratory distress and short limbs. Neonatal radiographs showed micromelic dwarfism and generalised demineralisation, especially at the ribs, long bones of both forearms and both fibulae. The spine showed a flattened shape. All long bones showed metaphyseal irregularities and flaring. Normal serum calcium and elevated serum phosphorus were found, while serum alkaline phosphatase was markedly reduced. A diagnosis of perinatal lethal hypophosphatasia was made. The aetiology, clinical manifestations, radiographical findings, laboratory assays, prenatal diagnosis and treatment of hypophosphatasia are discussed.

  9. Dyssegmental dysplasia in siblings: Prenatal ultrasonic diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, P.E. Jr.; Hauge, M.; Bang, J.

    1988-01-01

    Two cases of dyssegmental dysplasia (type Silverman-Handmaker) in siblings are presented. The first-born died at the age of 3 months and the second fetus was followed during pregnancy with ultrasound examinations. In the 20th week of gestation marked shortening of the extremities was found; a female infant showing the same radiologic bony malformations as the firstborn was born by cesarean section. These cases support the autosomal recessive inheritance and demonstrate the possibility of prenatal diagnosis in this type of micromelic dwarfism. (orig.)

  10. The SUPERMAN protein is an active repressor whose carboxy-terminal repression domain is required for the development of normal flowers.

    Science.gov (United States)

    Hiratsu, Keiichiro; Ohta, Masaru; Matsui, Kyoko; Ohme-Takagi, Masaru

    2002-03-13

    SUPERMAN was identified as a putative regulator of transcription that acts in floral development, but its function remains to be clarified. We demonstrate here that SUPERMAN is an active repressor whose repression domain is located in the carboxy-terminal region. Ectopic expression of SUPERMAN that lacked the repression domain resulted in a phenotype similar to that of superman mutants, demonstrating that the repression activity of SUPERMAN is essential for the development of normal flowers. Constitutive expression of SUPERMAN resulted in a severe dwarfism but did not affect cell size, indicating that SUPERMAN might regulate genes that are involved in cell division.

  11. A new gene, EVC2, is mutated in Ellis-van Creveld syndrome.

    Science.gov (United States)

    Galdzicka, M; Patnala, S; Hirshman, M G; Cai, J-F; Nitowsky, H; Egeland, J A; Ginns, E I

    2002-12-01

    Ellis-van Creveld syndrome (EvC; MIM 225500) is an autosomal recessive chondrodysplastic dwarfism. Thus far, the identified mutations in the EVC gene located on chromosome 4p16 have only accounted for illness in a small proportion of affected individuals. In this report we describe a novel gene, EVC2, that is mutated in an Ashkenazi individual with EvC syndrome. Our findings demonstrate for the first time that the heterogeneity observed in this disorder is not solely the result of mutations in a single gene.

  12. Correlative Light and Scanning X-Ray Scattering Microscopy of Healthy and Pathologic Human Bone Sections

    Science.gov (United States)

    Giannini, C.; Siliqi, D.; Bunk, O.; Beraudi, A.; Ladisa, M.; Altamura, D.; Stea, S.; Baruffaldi, F.

    2012-01-01

    Scanning small and wide angle X-ray scattering (scanning SWAXS) experiments were performed on healthy and pathologic human bone sections. Via crystallographic tools the data were transformed into quantitative images and as such compared with circularly polarized light (CPL) microscopy images. SWAXS and CPL images allowed extracting information of the mineral nanocrystalline phase embedded, with and without preferred orientation, in the collagen fibrils, mapping local changes at sub-osteon resolution. This favorable combination has been applied for the first time to biopsies of dwarfism syndrome and Paget's disease to shed light onto the cortical structure of natural bone in healthy and pathologic sections. PMID:22666538

  13. Endoscopic repair of transsellar transsphenoidal meningoencephalocele; case report and review of approaches

    Directory of Open Access Journals (Sweden)

    Maryam Jalessi, M.D.

    2015-06-01

    Full Text Available We present an extremely rare case of transsellar transsphenoidal meningoencephalocele in a 36-year-old woman with pituitary dwarfism complaining of nasal obstruction. Imaging studies showed a bony defect in the sellar floor and sphenoid sinus with huge nasopharyngeal mass and 3rd ventricle involvement. Using endoscopic endonasal approach the sac was partially removed and the defect was reconstructed with fat and fascial graft, and buttressed with titanium mesh and septal flap. Visual field improvement was noticed post-operatively and no complication was encountered during follow-up. So, endoscopic endonasal approach with partial resection of the sac is a safe and effective treatment for this disease

  14. Cockayne syndrome: report of a Brazilian family with confirmation of impaired RNA synthesis after UV-irradiation

    Directory of Open Access Journals (Sweden)

    Karam Simone M.

    2000-01-01

    Full Text Available Cockayne syndrome (CS is an autosomal recessive disorder characterized by dwarfism, growth deficiency, neurological deterioration, skin photosensitivity and a characteristic progressive facial appearance. In the present study we report the first Brazilian CS family in which diagnosis was confirmed by the demonstration of decreased RNA synthesis in cultured fibroblasts exposed to UV-C radiation. Despite the progressive course of the disease and the unavailability of an effective treatment, diagnosis may be very important for the benefits to be gained by the afflicted family from genetic counseling and/or prenatal diagnosis.

  15. Studies on Cinical , Haematological Aspects and Pathological Changes of Gastric Mucosa in Geophagia

    Directory of Open Access Journals (Sweden)

    S.N. SAYAR

    1975-01-01

    Full Text Available Geophagia characterized by, severe, anaemia, dwarfism, hypogonadism • and hepatosplenomegaly is sometimes seen in young patients (and children in Iran. 2 Haematological aspects of the syndrome are those of, severe, iron defi-crency anaemia3 Gastric biopsies and histological findings revealed superfi cial or atrophic gastritis showing some resemblance to those seen in pernicious anaemia. 4 Haematological features, anaemia ana many of the clinical signs of the syndrome were improved after appropriate iron therapy. 5 Histological changes of gastric mucosa improved, in 5 patients, 6 months after correction of the anaemia.

  16. Longitudinal tibial epiphyseal bracket in Nievergelt syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Burnstein, M.I.; De Smet, A.A.; Breed, A.L.; Thomas, J.R.; Hafez, G.R.

    1989-04-01

    A patient is described with lower extremity mesomelic dwarfism associated with bilateral congenital elbow, hip, and knee dislocations. Rhomboid-shaped tibiae and delayed ossification of the primary fibular ossification centers were demonstrated at birth. Plain films and magnetic resonance imaging revealed that the tibial deformities were due to the presence of longitudinal epiphyseal brackets. These brackets were observed at surgery and confirmed histologically. Recognition of the longitudinal epiphyseal bracket and its relationship to the tibial deformities seen in this patient with Nievergelt syndrome is important for planning surgical treatment. (orig.).

  17. Ellis van creveld syndrome with unusual association of essential infantile esotropia

    Directory of Open Access Journals (Sweden)

    D Das

    2010-01-01

    Full Text Available Ellis-van Creveld syndrome is a rare short-limbed disproportionate dwarfism characterized by postaxial polydactyly, several skeletal, oral mucosal and dental anomalies, nail dysplasia and in 50-60% cases of congenital cardiac defects. It is an autosomal recessive disorder with mutations of the EVC1 and EVC2 genes located on chromosome 4p16. Patients with this syndrome usually have a high mortality in early life due to cardiorespiratory problems. We present the case of a six- month-old female infant with Ellis-van Creveld syndrome - essential infantile esotropia, which has been infrequently documented in the literature.

  18. Bird-Headed Dwarf of Seckel

    Directory of Open Access Journals (Sweden)

    Harsha Vardhan B

    2007-05-01

    Full Text Available Seckel syndrome is an extremely rare inherited disorder characterized by growth delays prior to birth resulting in low birth weight. Growth delays continue after birth resulting in short stature (dwarfism. This syndrome is associated with an abnormally small head, varying degrees of mental retardation and unusual "beak like" protrusion of nose. Other facial features may include abnormally large eyes, a narrow face, malformed ears and an unusually small jaw. This syndrome has an autosomal recessive pattern of inheritance. A case of the Seckel syndrome is presented.

  19. Thanatophoric dysplasia: case report of an autopsy complemented by postmortem computed tomographic study

    Directory of Open Access Journals (Sweden)

    Éber Emanuel Mayoral

    2014-06-01

    Full Text Available Thanatophoric dysplasia (TD is one of the most common lethal skeletal dysplasias, which was first designated as thanatophoric dwarfism and described in 1967. The authors report a case of a Caucasian girl with TD, born to a 31-year-old woman without comorbidities. The newborn presented respiratory distress immediately after delivery, progressing to death in less than 2 hours. An autopsy was carried out after postmortem tomographic examination. The autopsy findings depicted extensive malformations of the skeletal system and the brain. The aim of this report is to discuss the pathogenesis and correlate the morphologic features of TD that were disclosed at the tomography and the autopsy.

  20. New type of spondylo-metaphyseal dysplasia - Algerian type. Report of five cases

    Energy Technology Data Exchange (ETDEWEB)

    Kozlowski, K.; Bacha, L.; Massen, R.; Ayati, M.; Sator, S.; Brahimi, L.

    1988-04-01

    A new, dominantly inherited, severe form of spondylometaphyseal dysplasia in five members of an Algerian family is reported. Another child, not investigated, was also probably affected. The disease is characterised by a unique clinical and radiological set of features: dwarfism, genu valgum deformity, progressive kypho-scoliosis, wrist deformity, myopia and severe metaphyseal dysplasia, with moderate spinal changes and minimal changes in the hands and feet. In view of the geographical localisation of the disorder and the anatomical distribution we propose the name Algerian type of spondylo-metaphyseal dysplasia.

  1. [The history of the pituitary gland: evolution of mental representation and concepts over time].

    Science.gov (United States)

    Jedidi, H; Jedidi, Z; Beckers, A

    2014-02-01

    The hypothalamo pituitary axis, as the true conductor of the endocrine orchestra, is frequently involved in a large variety of pathological conditions such as acromegaly, behavioral disorders, obesity or dwarfism. It is paradoxical to note that, in spite of its importance, this system has been almost ignored by the physiologists of the late centuries. From the physiological conceptions of the physicians and philosophers of antiquity to the theories of the medieval and of the Renaissance physiologists, we will try to understand why the role of pituitary remained so long unrecognized.

  2. Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy.

    Science.gov (United States)

    Martin, Carol-Anne; Ahmad, Ilyas; Klingseisen, Anna; Hussain, Muhammad Sajid; Bicknell, Louise S; Leitch, Andrea; Nürnberg, Gudrun; Toliat, Mohammad Reza; Murray, Jennie E; Hunt, David; Khan, Fawad; Ali, Zafar; Tinschert, Sigrid; Ding, James; Keith, Charlotte; Harley, Margaret E; Heyn, Patricia; Müller, Rolf; Hoffmann, Ingrid; Daire, Valérie Cormier; Dollfus, Hélène; Dupuis, Lucie; Bashamboo, Anu; McElreavey, Kenneth; Kariminejad, Ariana; Mendoza-Londono, Roberto; Moore, Anthony T; Saggar, Anand; Schlechter, Catie; Weleber, Richard; Thiele, Holger; Altmüller, Janine; Höhne, Wolfgang; Hurles, Matthew E; Noegel, Angelika Anna; Baig, Shahid Mahmood; Nürnberg, Peter; Jackson, Andrew P

    2014-12-01

    Centrioles are essential for ciliogenesis. However, mutations in centriole biogenesis genes have been reported in primary microcephaly and Seckel syndrome, disorders without the hallmark clinical features of ciliopathies. Here we identify mutations in the genes encoding PLK4 kinase, a master regulator of centriole duplication, and its substrate TUBGCP6 in individuals with microcephalic primordial dwarfism and additional congenital anomalies, including retinopathy, thereby extending the human phenotypic spectrum associated with centriole dysfunction. Furthermore, we establish that different levels of impaired PLK4 activity result in growth and cilia phenotypes, providing a mechanism by which microcephaly disorders can occur with or without ciliopathic features.

  3. Naumoff short-rib polydactyly syndrome compounded with Mohr oral-facial-digital syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Young, L.W.; Wilhelm, L.L. [Loma Linda Univ., CA (United States). Medical Center; Zuppan, C.W. [Div. of Pediatric Pathology, Loma Linda University Medical Center, CA (United States); Clark, R. [Div. of Medical Genetics, Loma Linda University Medical Center, CA (United States)

    2001-01-01

    A stillborn baby boy had findings of severe constitutional dwarfism with short limbs, short ribs, and polydactyly that were consistent with Naumoff (type III) short-rib polydactyly syndrome. He also had additional congenital anomalies, including cleft palate, notching of the upper lip, small tongue with accessory sublingual tissue. These oral and pharyngeal anomalies were consistent with Mohr (type II) oral-facial-digital syndrome. We suggest the stillborn infant represented a compound of Naumoff short-rib polydactyly syndrome (SRPS-III) and Mohr oral-facial-digital syndrome (OFDS-II). (orig.)

  4. Generation of Evc2/Limbin global and conditional KO mice and its roles during mineralized tissue formation.

    Science.gov (United States)

    Zhang, Honghao; Takeda, Haruko; Tsuji, Takehito; Kamiya, Nobuhiro; Rajderkar, Sudha; Louie, Ke'Ale; Collier, Crystal; Scott, Greg; Ray, Manas; Mochida, Yoshiyuki; Kaartinen, Vesa; Kunieda, Tetsuo; Mishina, Yuji

    2015-07-28

    Ellis-van Creveld (EvC) syndrome (OMIM 225500) is an autosomal recessive disease characterized with chondrodysplastic dwarfism in association with abnormalities in oral cavity. Ciliary proteins EVC and EVC2 have been identified as causative genes and they play an important role on Hedgehog signal transduction. We have also identified a causative gene LIMBIN for bovine chondrodysplastic dwarfism (bcd) that is later identified as the bovine ortholog of EVC2. Here, we report generation of conventional and conditional mutant Evc2/Limbin alleles that mimics mutations found in EvC patients and bcd cattle. Resulted homozygous mice showed no ciliary localization of EVC2 and EVC and displayed reduced Hedgehog signaling activity in association with skeletal and oral defects similar to the EvC patients. Cartilage-specific disruption of Evc2/Limbin resulted in similar but milder skeletal defects, whereas osteoblast-specific disruption did not cause overt changes in skeletal system. Neural crest-specific disruption of Evc2/Limbin resulted in defective incisor growth similar to that seen in conventional knockouts; however, differentiation of amelobolasts was relatively normal in the conditional knockouts. These results showcased functions of EVC2/LIMBIN during formation of mineralized tissues. Availability of the conditional allele for this gene should facilitate further detailed analyses of the role of EVC2/LIMBIN in pathogenesis of EvC syndrome. genesis, 2015. © 2015 Wiley Periodicals, Inc.

  5. An infant with cartilage-hair hypoplasia due to a novel homozygous mutation in the promoter region of the RMRP gene associated with chondrodysplasia and severe immunodeficiency.

    Science.gov (United States)

    Vatanavicharn, N; Visitsunthorn, N; Pho-iam, T; Jirapongsananuruk, O; Pacharn, P; Chokephaibulkit, K; Limwongse, C; Wasant, P

    2010-01-01

    Cartilage-hair hypoplasia (CHH) is a rare autosomal-recessive disorder characterized by short-limbed dwarfism, sparse hair, and immune deficiency. It is caused by mutations in the RMRP gene, which encodes the RNA component of the mitochondrial RNA-processing ribonuclease (RNase MRP). Several mutations have been identified in its promoter region or transcribed sequence. However, homozygous mutations in the promoter region have been only reported in a patient with primary immunodeficiency without other features of CHH. We report on a Thai girl who first presented with chronic diarrhea, recurrent pneumonia, and severe failure to thrive, without apparently disproportionate dwarfism. The diagnosis of CHH was made after the severe wasting was corrected, and disproportionate growth became noticeable. The patient had the typical features of CHH, including sparse hair and metaphyseal abnormalities. The immunologic profiles were consistent with combined immune deficiency. Mutation analysis identified a novel homozygous mutation, g.-19_-25 dupACTACTC, in the promoter region of the RMRP gene. Identification of the mutation enabled us to provide a prenatal diagnosis in the subsequent pregnancy. This patient is the first CHH case with the characteristic features due to the homozygous mutation in the promoter region of the RMRP gene. The finding of severe immunodeficiency supports that promoter mutations markedly disrupt mRNA cleavage function, which causes cell-cycle impairment.

  6. Cockayne's syndrome: correlation of clinical features with cellular sensitivity of RNA synthesis to UV irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lehmann, A.R.; Thompson, A.F.; Harcourt, S.A. (Medical Research Council, Brighton (United Kingdom). Cell Mutation Unit); Stefanini, Miria (Consiglio Nazionale delle Ricerche, Pavia (Italy). Ist. di Genetica Biochimica ed Evoluzionistica); Norris, P.G. (Addenbrooke' s Hospital, Cambridge (United Kingdom))

    1993-08-01

    Cockayne's syndrome (CS) is a rare autosomal recessive disorder with dwarfism, mental retardation, and otherwise clinically heterogeneous features. In cultured CS fibroblasts, the failure of RNA synthesis to recover to normal rates after UV-C irradiation provides a useful and relatively simple diagnostic test. We have measured post-UV-C RNA synthesis in 52 patients for whom a clinical diagnosis of CS was considered a possibility. Twenty-nine patients showed the defect characteristic of CS cells, and 23 had a normal response. We have attempted to correlate the cellular diagnosis with the different clinical features of the disorder. Clinical details of the patients were obtained from referring clinicians in the form of a questionnaire. Our results show that, apart from the cardinal features of dwarfism and mental retardation, sun sensitivity correlated best with a positive cellular diagnosis. Pigmentary retinopathy, gait defects, and dental caries were also good positive indicators, although several patients with a positive cellular diagnosis did not have these features. (Author).

  7. An A20/AN1-type zinc finger protein modulates gibberellins and abscisic acid contents and increases sensitivity to abiotic stress in rice (Oryza sativa).

    Science.gov (United States)

    Zhang, Ye; Lan, Hongxia; Shao, Qiaolin; Wang, Ruqin; Chen, Hui; Tang, Haijuan; Zhang, Hongsheng; Huang, Ji

    2016-01-01

    The plant hormones gibberellins (GA) and abscisic acid (ABA) play important roles in plant development and stress responses. Here we report a novel A20/AN1-type zinc finger protein ZFP185 involved in GA and ABA signaling in the regulation of growth and stress response. ZFP185 was constitutively expressed in various rice tissues. Overexpression of ZFP185 in rice results in a semi-dwarfism phenotype, reduced cell size, and the decrease of endogenous GA3 content. By contrast, higher GA3 content was observed in RNAi plants. The application of exogenous GA3 can fully rescue the semi-dwarfism phenotype of ZFP185 overexpressing plants, suggesting the negative role of ZFP185 in GA biosynthesis. Besides GA, overexpression of ZFP185 decreased ABA content and expression of several ABA biosynthesis-related genes. Moreover, it was found that ZFP185, unlike previously known A20/AN1-type zinc finger genes, increases sensitivity to drought, cold, and salt stresses, implying the negative role of ZFP185 in stress tolerance. ZFP185 was localized in the cytoplasm and lacked transcriptional activation potential. Our study suggests that ZFP185 regulates plant growth and stress responses by affecting GA and ABA biosynthesis in rice.

  8. The dwarf phenotype in GH240B mice, haploinsufficient for the autism candidate gene Neurobeachin, is caused by ectopic expression of recombinant human growth hormone.

    Directory of Open Access Journals (Sweden)

    Kim Nuytens

    Full Text Available Two knockout mouse models for the autism candidate gene Neurobeachin (Nbea have been generated independently. Although both models have similar phenotypes, one striking difference is the dwarf phenotype observed in the heterozygous configuration of the GH240B model that is generated by the serendipitous insertion of a promoterless human growth hormone (hGH genomic fragment in the Nbea gene. In order to elucidate this discrepancy, the dwarfism present in this Nbea mouse model was investigated in detail. The growth deficiency in Nbea+/- mice coincided with an increased percentage of fat mass and a decrease in bone mineral density. Low but detectable levels of hGH were detected in the pituitary and hypothalamus of Nbea+/- mice but not in liver, hippocampus nor in serum. As a consequence, several members of the mouse growth hormone (mGH signaling cascade showed altered mRNA levels, including a reduction in growth hormone-releasing hormone mRNA in the hypothalamus. Moreover, somatotrope cells were less numerous in the pituitary of Nbea+/- mice and both contained and secreted significantly less mGH resulting in reduced levels of circulating insulin-like growth factor 1. These findings demonstrate that the random integration of the hGH transgene in this mouse model has not only inactivated Nbea but has also resulted in the tissue-specific expression of hGH causing a negative feedback loop, mGH hyposecretion and dwarfism.

  9. Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice

    Science.gov (United States)

    Csiszar, Anna; Labinskyy, Nazar; Perez, Viviana; Recchia, Fabio A.; Podlutsky, Andrej; Mukhopadhyay, Partha; Losonczy, Gyorgy; Pacher, Pal; Austad, Steven N.; Bartke, Andrzej; Ungvari, Zoltan

    2008-01-01

    Hypopituitary Ames dwarf mice have low circulating growth hormone (GH)/IGF-I levels, and they have extended longevity and exhibit many symptoms of delayed aging. To elucidate the vascular consequences of Ames dwarfism we compared endothelial O2•− and H2O2 production, mitochondrial reactive oxygen species (ROS) generation, expression of antioxidant enzymes, and nitric oxide (NO) production in aortas of Ames dwarf and wild-type control mice. In Ames dwarf aortas endothelial O2•− and H2O2 production and ROS generation by mitochondria were enhanced compared with those in vessels of wild-type mice. In Ames dwarf aortas there was a less abundant expression of Mn-SOD, Cu,Zn-SOD, glutathione peroxidase (GPx)-1, and endothelial nitric oxide synthase (eNOS). NO production and acetylcholine-induced relaxation were also decreased in aortas of Ames dwarf mice. In cultured wild-type mouse aortas and in human coronary arterial endothelial cells treatment with GH and IGF significantly reduced cellular O2•− and H2O2 production and ROS generation by mitochondria and upregulated expression of Mn-SOD, Cu,Zn-SOD, GPx-1, and eNOS. Thus GH and IGF-I promote antioxidant phenotypic changes in the endothelial cells, whereas Ames dwarfism leads to vascular oxidative stress. PMID:18757483

  10. The dwarf phenotype in GH240B mice, haploinsufficient for the autism candidate gene Neurobeachin, is caused by ectopic expression of recombinant human growth hormone.

    Science.gov (United States)

    Nuytens, Kim; Tuand, Krizia; Fu, Quili; Stijnen, Pieter; Pruniau, Vincent; Meulemans, Sandra; Vankelecom, Hugo; Creemers, John W M

    2014-01-01

    Two knockout mouse models for the autism candidate gene Neurobeachin (Nbea) have been generated independently. Although both models have similar phenotypes, one striking difference is the dwarf phenotype observed in the heterozygous configuration of the GH240B model that is generated by the serendipitous insertion of a promoterless human growth hormone (hGH) genomic fragment in the Nbea gene. In order to elucidate this discrepancy, the dwarfism present in this Nbea mouse model was investigated in detail. The growth deficiency in Nbea+/- mice coincided with an increased percentage of fat mass and a decrease in bone mineral density. Low but detectable levels of hGH were detected in the pituitary and hypothalamus of Nbea+/- mice but not in liver, hippocampus nor in serum. As a consequence, several members of the mouse growth hormone (mGH) signaling cascade showed altered mRNA levels, including a reduction in growth hormone-releasing hormone mRNA in the hypothalamus. Moreover, somatotrope cells were less numerous in the pituitary of Nbea+/- mice and both contained and secreted significantly less mGH resulting in reduced levels of circulating insulin-like growth factor 1. These findings demonstrate that the random integration of the hGH transgene in this mouse model has not only inactivated Nbea but has also resulted in the tissue-specific expression of hGH causing a negative feedback loop, mGH hyposecretion and dwarfism.

  11. Evaluation of the therapeutic potential of a CNP analog in a Fgfr3 mouse model recapitulating achondroplasia.

    Science.gov (United States)

    Lorget, Florence; Kaci, Nabil; Peng, Jeff; Benoist-Lasselin, Catherine; Mugniery, Emilie; Oppeneer, Todd; Wendt, Dan J; Bell, Sean M; Bullens, Sherry; Bunting, Stuart; Tsuruda, Laurie S; O'Neill, Charles A; Di Rocco, Federico; Munnich, Arnold; Legeai-Mallet, Laurence

    2012-12-07

    Achondroplasia (ACH), the most common form of dwarfism, is an inherited autosomal-dominant chondrodysplasia caused by a gain-of-function mutation in fibroblast-growth-factor-receptor 3 (FGFR3). C-type natriuretic peptide (CNP) antagonizes FGFR3 downstream signaling by inhibiting the pathway of mitogen-activated protein kinase (MAPK). Here, we report the pharmacological activity of a 39 amino acid CNP analog (BMN 111) with an extended plasma half-life due to its resistance to neutral-endopeptidase (NEP) digestion. In ACH human growth-plate chondrocytes, we demonstrated a decrease in the phosphorylation of extracellular-signal-regulated kinases 1 and 2, confirming that this CNP analog inhibits fibroblast-growth-factor-mediated MAPK activation. Concomitantly, we analyzed the phenotype of Fgfr3(Y367C/+) mice and showed the presence of ACH-related clinical features in this mouse model. We found that in Fgfr3(Y367C/+) mice, treatment with this CNP analog led to a significant recovery of bone growth. We observed an increase in the axial and appendicular skeleton lengths, and improvements in dwarfism-related clinical features included flattening of the skull, reduced crossbite, straightening of the tibias and femurs, and correction of the growth-plate defect. Thus, our results provide the proof of concept that BMN 111, a NEP-resistant CNP analog, might benefit individuals with ACH and hypochondroplasia. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  12. Intermittent PTH (1-34) injection rescues the retarded skeletal development and postnatal lethality of mice mimicking human achondroplasia and thanatophoric dysplasia.

    Science.gov (United States)

    Xie, Yangli; Su, Nan; Jin, Min; Qi, Huabing; Yang, Junbao; Li, Can; Du, Xiaolan; Luo, Fengtao; Chen, Bo; Shen, Yue; Huang, Haiyang; Xian, Cory J; Deng, Chuxia; Chen, Lin

    2012-09-15

    Achondroplasia (ACH) and thanatophoric dysplasia (TD) are caused by gain-of-function mutations of fibroblast growth factor receptor 3 (FGFR3) and they are the most common forms of dwarfism and lethal dwarfism, respectively. Currently, there are few effective treatments for ACH. For the neonatal lethality of TD patients, no practical effective therapies are available. We here showed that systemic intermittent PTH (1-34) injection can rescue the lethal phenotype of TD type II (TDII) mice and significantly alleviate the retarded skeleton development of ACH mice. PTH-treated ACH mice had longer naso-anal length than ACH control mice, and the bone lengths of humeri and tibiae were rescued to be comparable with those of wild-type control mice. Our study also found that the premature fusion of cranial synchondroses in ACH mice was partially corrected after the PTH (1-34) treatment, suggesting that the PTH treatment may rescue the progressive narrowing of neurocentral synchondroses that cannot be readily corrected by surgery. In addition, we found that the PTH treatment can improve the osteopenia and bone structure of ACH mice. The increased expression of PTHrP and down-regulated FGFR3 level may be responsible for the positive effects of PTH on bone phenotype of ACH and TDII mice.

  13. Skeletal manifestations of juvenile hypothyroidism and the impact of treatment on skeletal system

    Directory of Open Access Journals (Sweden)

    Manish Gutch

    2013-01-01

    Full Text Available Thyroid hormone mediates growth and development of the skeleton through its direct effects and through its permissive effects on growth hormone. The effect of hypothyroidism on bone is well described in congenital hypothyroidism, but the impact of thyroid hormone deficiency on a growing skeleton, as it happens with juvenile hypothyroidism, is less defined. In addition, the extent to which the skeletal defects of juvenile hypothyroidism revert on the replacement of thyroid hormone is not known. A study was undertaken in 29 juvenile autoimmune hypothyroid patients to study the skeletal manifestations of juvenile hypothyroidism and the impact of treatment of hypothyroidism on the skeletal system of juvenile patients. Hypothyroidism has a profound impact on the skeletal system and delayed bone age, dwarfism, and thickened bands at the metaphyseal ends being the most common findings. Post treatment, skeletal findings like delayed bone age and dwarfism improved significantly, but there were no significant changes in enlargement of sella, presence of wormian bones, epihyseal dysgenesis, vertebral changes and thickened band at the metaphyseal ends. With the treatment of hypothyroidism, there is an exuberant advancement of bone age, the catch up of bone age being approximately double of the chronological age advancement.

  14. SUMOylation regulates nuclear localization and stability of TRAIP/RNF206

    Energy Technology Data Exchange (ETDEWEB)

    Park, I. Seul; Han, Ye gi; Chung, Hee Jin [Department of Biological Sciences, Sungkyunkwan University (SKKU), Suwon 440-746 (Korea, Republic of); Jung, Yong Woo [College of Pharmacy, Korea University, Sejong City 339-700 (Korea, Republic of); Kim, Yonghwan, E-mail: yhkim@sookmyung.ac.kr [Department of Biological Sciences, Sookmyung Women' s University, Seoul 04310 (Korea, Republic of); Kim, Hongtae, E-mail: khtcat@skku.edu [Department of Biological Sciences, Sungkyunkwan University (SKKU), Suwon 440-746 (Korea, Republic of)

    2016-02-19

    TRAIP/RNF206 plays diverse roles in cell cycle progression, DNA damage response, and DNA repair pathways. Physiological importance of TRAIP is highlighted by the identification of pathogenic mutations of TRAIP gene in patients diagnosed with primordial dwarfism. Although the diverse functions of TRAIP in the nucleus have been well characterized, molecular mechanism of TRAIP retention in the nucleus has not been determined. Here, we discovered that TRAIP is post-translationally modified by the small ubiquitin-like protein (SUMO). In addition, we identified five SUMOylation sites in TRAIP, and successfully generated SUMOylation deficient mutant of TRAIP. In an attempt to define the functional roles of TRAIP SUMOylation, we discovered that SUMOylation deficient TRAIP is not retained in the nucleus. In addition, protein stability of SUMOylation deficient TRAIP is lower than wild type TRAIP, demonstrating that SUMOylation is critical for both proper subcellular localization and protein stability of TRAIP. Taken together, these findings improve the understanding clinical implication of TRAIP in various diseases including primordial dwarfism and cancers. - Highlights: • TRAIP is post-translationally modified by SUMO. • SUMOylation affects subcellular localization of TRAIP. • SUMOylation regulates protein stability of TRAIP.

  15. Fenarimol, a Pyrimidine-Type Fungicide, Inhibits Brassinosteroid Biosynthesis

    Directory of Open Access Journals (Sweden)

    Keimei Oh

    2015-07-01

    Full Text Available The plant steroid hormone brassinosteroids (BRs are important signal mediators that regulate broad aspects of plant growth and development. With the discovery of brassinoazole (Brz, the first specific inhibitor of BR biosynthesis, several triazole-type BR biosynthesis inhibitors have been developed. In this article, we report that fenarimol (FM, a pyrimidine-type fungicide, exhibits potent inhibitory activity against BR biosynthesis. FM induces dwarfism and the open cotyledon phenotype of Arabidopsis seedlings in the dark. The IC50 value for FM to inhibit stem elongation of Arabidopsis seedlings grown in the dark was approximately 1.8 ± 0.2 μM. FM-induced dwarfism of Arabidopsis seedlings could be restored by brassinolide (BL but not by gibberellin (GA. Assessment of the target site of FM in BR biosynthesis by feeding BR biosynthesis intermediates indicated that FM interferes with the side chain hydroxylation of BR biosynthesis from campestanol to teasterone. Determination of the binding affinity of FM to purified recombinant CYP90D1 indicated that FM induced a typical type II binding spectrum with a Kd value of approximately 0.79 μM. Quantitative real-time PCR analysis of the expression level of the BR responsive gene in Arabidopsis seedlings indicated that FM induces the BR deficiency in Arabidopsis.

  16. A Case Report of Camptomelic Dysplasia

    Directory of Open Access Journals (Sweden)

    Zia Islami

    2011-09-01

    Full Text Available Camptomelic Dysplasia (CMD is a rare autosomal dominant congenital dwarfism characterized by shortness and bowing of long bones (camptomelia and other severe skeletal and extra skeletal malformations. CMD is generally considered to be lethal and the majority of cases die in the neonatal period due to respiratory insufficiency.We hereunder report a term male neonate with characteristic clinical and radiological findings of CMD, hydrocephaly, no sex reversal, and a negative family history of skeletal problems who was born to non-consanguineous  healthy parents and was admitted to Shahid Sadoughi Hospital, Yazd, Iran,immediately after birth due to respiratory distress.The patient required continuous mechanical ventilation support and all attempts to reduce respiratory support failed and the patient died on the 21th day of his life. Camptomelic Dysplasia is a terrible experience for parents; thus, prenatal diagnosis of CMD by ultrasound is essential and mandatory for a better therapeutic intervention.Key words: Camptomelic dysplasia; dwarfism/congenital; bowing of longbones; sex-reversal

  17. Preserved fertility in a non-mosaic Klinefelter patient with a mutation in the fibroblast growth factor receptor 3 gene

    DEFF Research Database (Denmark)

    Juul, A; Aksglaede, L; Lund, A M;

    2007-01-01

    receptor 3 (FGFR3) gene, which is a gain-of-function mutation resulting in achondroplasia. The patient had phenotypic characteristics of achondroplasia (e.g. short limbed dwarfism and frontal bossing). Testicular volume was 8 ml at 27 years of age and repeated semen samples showed sperm concentrations of 0...... a child from a spontaneous pregnancy. The observed testicular size and function in our patient contrast the typical findings in classical Klinefelter syndrome. We speculate that the alteration of FGFR3 protein function in our Klinefelter patient alleviated the destruction of the seminiferous tubules...... and may suggest that the fibroblast growth factor family has a pleiotrophic function in human spermatogonia, which physiologically express FGFR3....

  18. A Review of Selected Genes with Known Effects on Performance and Health of Cattle

    Science.gov (United States)

    Casas, Eduardo; Kehrli, Marcus E.

    2016-01-01

    There are genetic conditions that influence production in dairy and beef cattle. The objective of this review was to describe relevant genetic conditions that have been associated with productivity and health in cattle. Genes or genomic regions that have been identified as a candidate for the condition will be included, and the genetic basis of the condition will be defined. Genes and genetic conditions included in this review are bovine leukocyte adhesion deficiency, deficiency of the uridine monophosphate synthase, bovine chronic interstitial nephritis, horn development, myostatin, complex vertebral malformation, leptin, osteopetrosis, apoptosis peptide activating factor 1, chondrodysplastic dwarfism, caseins, calpastatin, umbilical hernia, lactoglobulin, citrullinemia, cholesterol deficiency, prions, thyroglobulin, diacylglycerol acyltransferase, syndactyly, maple syrup urine disease, slick hair, Factor XI deficiency, and μ-Calpain. This review is not meant to be comprehensive, and relevant information is provided to ascertain genetic markers associated with the conditions. PMID:28018909

  19. Magnetic resonance imaging in patients with panhypopituitarism

    Energy Technology Data Exchange (ETDEWEB)

    Pozzi Mucelli, R.S. [Ist. di Radiologia, Univ. di Trieste, Ospedale di Cattinara (Italy); Frezza, F. [Ist. di Radiologia, Univ. di Trieste, Ospedale di Cattinara (Italy); Magnaldi, S. [Ist. di Radiologia, Univ. di Trieste, Ospedale di Cattinara (Italy); Proto, G. [Servizio di Endocrinologia, Ospedale Civile di Udine (Italy)

    1992-02-01

    Primary panhypopituitarism consists of functional deficiency of the anterior pituitary lobe, which appears during infancy or adolescence. The magnetic resonance findings in 10 patients with a history of primary hypopituitarism are presented. The findings include: reduced pituitary size in all cases; partially (8 cases) or totally (2 cases) empty sella; thin (4 cases), partially visible (3 cases) or absent (2 cases) pituitary stalk; absence of the posterior lobe in 9 cases; bright spot corresponding to an ectopic posterior lobe in 8 cases. These findings are similar to those already reported in pituitary dwarfism and may help understanding of the pathogenesis of the disease, which seems to be related to a pituitary stalk lesion. (orig.)

  20. Identification of a Novel Mutation in the COL2A1 Gene in a Chinese Family with Spondyloepiphyseal Dysplasia Congenita.

    Directory of Open Access Journals (Sweden)

    Xiangjun Huang

    Full Text Available Spondyloepiphyseal dysplasia congenita (SEDC is an autosomal dominant chondrodysplasia characterized by disproportionate short-trunk dwarfism, skeletal and vertebral deformities. Exome sequencing and Sanger sequencing were performed in a Chinese Han family with typical SEDC, and a novel mutation, c.620G>A (p.Gly207Glu, in the collagen type II alpha-1 gene (COL2A1 was identified. The mutation may impair protein stability, and lead to dysfunction of type II collagen. Family-based study suggested that the mutation is a de novo mutation. Our study extends the mutation spectrum of SEDC and confirms genotype-phenotype relationship between mutations at glycine in the triple helix of the alpha-1(II chains of the COL2A1 and clinical findings of SEDC, which may be helpful in the genetic counseling of patients with SEDC.

  1. Novel duck parvovirus identified in Cherry Valley ducks (Anas platyrhynchos domesticus), China.

    Science.gov (United States)

    Li, Chuanfeng; Li, Qi; Chen, Zongyan; Liu, Guangqing

    2016-10-01

    An unknown infectious disease in Cherry Valley ducks (Anas platyrhynchos domesticus) characterized by short beak and strong growth retardation occurred in China during 2015. The causative agent of this disease, tentatively named duck short beak and dwarfism syndrome (DSBDS), as well as the evolutionary relationships between this causative agent and all currently known avian-origin parvoviruses were clarified by virus isolation, transmission electron microscope (TEM) observation, analysis of nuclear acid type, (RT-)PCR identification, whole genome sequencing, and NS1 protein sequences-based phylogenetic analyses. The results indicated that the causative agent of DSBDS is closely related with the goose parvovirus-like virus, which is divergent from all currently known avian-origin parvoviruses and should be a novel duck parvovirus (NDPV). Copyright © 2016 Elsevier B.V. All rights reserved.

  2. 棕榈藤保护与开发面临的挑战:指南与政策%Challenges of Rattan Conservation and Development Guidelines and Policies

    Institute of Scientific and Technical Information of China (English)

    C. Lakshmana

    2008-01-01

    Rattan Canes are mainly distributed in the tropical forests, with limited distribution in temperate forests. They are widely used to decorate houses and offices with elegant, attractive furniture. Their attraction and durability is mainly responsible for its immense demand resulting in overexploitation, reduced productivity and gradual disappearance from accessible areas. Many species have reached such low numbers, that they may not be able to naturally regenerate themselves further. Rattan is facing the challenges of fire, shifting cultivation, over-exploitation, shrinking forests, dwarfism/prolonged rosette stage, etc.%阐述了世界棕榈藤的分布、资源状况、一些国家经营与利用现状以及棕榈藤在缓解气候变化中的作用,并对棕榈藤的保护和研究提出了建议.

  3. The pleiotropic ABNORMAL FLOWER AND DWARF1 affects plant height, floral development and grain yield in rice

    Institute of Scientific and Technical Information of China (English)

    Deyong Ren; Li Zhu; Zhenyu Gao; Guojun Dong; Guangheng Zhang; Longbiao Guo; Dali Zeng; and Qian Qian; Yuchun Rao; Liwen Wu; Qiankun Xu; Zizhuang Li; Haiping Yu; Yu Zhang; Yujia Leng; Jiang Hu

    2016-01-01

    Moderate plant height and successful establish-ment of reproductive organs play pivotal roles in rice grain production. The molecular mechanism that controls the two aspects remains unclear in rice. In the present study, we characterized a rice gene, ABNORMAL FLOWER AND DWARF1 (AFD1) that determined plant height, floral development and grain yield. The afd1 mutant showed variable defects including the dwarfism, long panicle, low seed setting and reduced grain yield. In addition, abnormal floral organs were also observed in the afd1 mutant including slender and thick hulls, and hull-like lodicules. AFD1 encoded a DUF640 domain protein and was ex-pressed in all tested tissues and organs. Subcellular localization showed AFD1-green fluorescent fusion protein (GFP) was localized in the nucleus. Meantime, our results suggested that AFD1 regulated the expression of cell division and expansion related genes.

  4. Mighty Dwarfs: Arabidopsis Autoimmune Mutants and Their Usages in Genetic Dissection of Plant Immunity

    Science.gov (United States)

    van Wersch, Rowan; Li, Xin; Zhang, Yuelin

    2016-01-01

    Plants lack the adaptive immune system possessed by mammals. Instead they rely on innate immunity to defend against pathogen attacks. Genomes of higher plants encode a large number of plant immune receptors belonging to different protein families, which are involved in the detection of pathogens and activation of downstream defense pathways. Plant immunity is tightly controlled to avoid activation of defense responses in the absence of pathogens, as failure to do so can lead to autoimmunity that compromises plant growth and development. Many autoimmune mutants have been reported, most of which are associated with dwarfism and often spontaneous cell death. In this review, we summarize previously reported Arabidopsis autoimmune mutants, categorizing them based on their functional groups. We also discuss how their obvious morphological phenotypes make them ideal tools for epistatic analysis and suppressor screens, and summarize genetic screens that have been carried out in various autoimmune mutant backgrounds. PMID:27909443

  5. Ichthyosis vulgaris and pycnodysostosis: an unusual occurrence.

    Science.gov (United States)

    Kshirsagar, Vinayak Y; Ahmed, Minhajuddin; Nagarsenkar, Suhel; Sahoo, Kulmani; Shah, Kuldeep B

    2012-01-01

    Pycnodysostosis is a rare autosomal recessive disorder whose gene responsible for this phenotype (CTSK), mapped to human chromosome 1q21, code for the enzyme cathepsin K, a lysosomal cysteine protease; with an estimated incidence of 1.7 per 1 million births. This clinical entity includes micromelic dwarfism, increased radiological bone density, dysplasia of the skull, acro-osteolysis, straightening of the mandibular angle and in some cases, dysplasia of the acromial end of the clavicle. Oral and maxillo-facial manifestations of this disease are very clear. Herein we reported a case of pycnodysostosis, showing short stature with widening of the sutures, unfused anterior and posterior fontanelles, crowding of teeth with dental caries and typical radiological features associated with ichthyosis vulgaris and palmoplantar keratoderma.

  6. Rambam-Hasharon syndrome of psychomotor retardation, short stature, defective neutrophil motility, and Bombay phenotype.

    Science.gov (United States)

    Frydman, M; Etzioni, A; Eidlitz-Markus, T; Avidor, I; Varsano, I; Shechter, Y; Orlin, J B; Gershoni-Baruch, R

    1992-10-01

    We describe 2 Arab patients, both offspring of unrelated consanguineous matings, with unusual facial appearance, severe mental retardation, microcephaly, cortical atrophy, seizures, hypotonia, dwarfism, and recurrent infections with neutrophilia. Neutrophil motility was markedly decreased but the opsonophagocytic activity was normal. Both patients lack the red blood cell (RBC) H antigen and manifest the Bombay (hh) phenotype. Familial endocardial fibroelastosis and familial tetralogy of Fallot segregated independently in one family. The occurrence of the same syndrome in 2 unrelated families suggests that the various aspects of the disorder are the pleiotropic effects of a single mutation. Homozygosity-by-descent for a deletion involving contiguous genes may explain the findings in this syndrome. Alternatively, a mutation which involves an ubiquitous GDP fucose donor rather than the enzyme (alpha 2-L-fucosyltransferase) or its substrate (glcNAc) may account for the pleiotropic manifestations in this syndrome.

  7. Gibberellic Acid: A Key Phytohormone for Spikelet Fertility in Rice Grain Production

    Science.gov (United States)

    Kwon, Choon-Tak; Paek, Nam-Chon

    2016-01-01

    The phytohormone gibberellic acid (GA) has essential signaling functions in multiple processes during plant development. In the “Green Revolution”, breeders developed high-yield rice cultivars that exhibited both semi-dwarfism and altered GA responses, thus improving grain production. Most studies of GA have concentrated on germination and cell elongation, but GA also has a pivotal role in floral organ development, particularly in stamen/anther formation. In rice, GA signaling plays an important role in spikelet fertility; however, the molecular genetic and biochemical mechanisms of GA in male fertility remain largely unknown. Here, we review recent progress in understanding the network of GA signaling and its connection with spikelet fertility, which is tightly associated with grain productivity in cereal crops. PMID:27223278

  8. The GH-IGF1 axis and longevity. The paradigm of IGF1 deficiency.

    Science.gov (United States)

    Laron, Zvi

    2008-01-01

    Primary or secondary IGF1 deficiency has been implicated in shortening of lifespan. This paper reviews available data on the influence of IGF1 deficiency on lifespan and longevity in animals and man. It has been shown that inactivation of the IGF1 gene or of the GH receptor in both invertebrates (C-elegans, flies-Drosphila) and rodents (mice and rats), leading to IGF1 deficiency, prolong life, particularly in females. In man, evaluation of the 2 largest cohorts of patients with Laron syndrome (inactive GH receptor resulting in IGF1 deficiency) in Israel and Ecuador revealed that despite their dwarfism and marked obesity, patients are alive at the ages of 75-78 years, with some having reached even more advanced ages. It is assumed that a major contributing factor is their protection from cancer, a major cause of death in the general population.

  9. Insulin-like growth factor-I treatment of children with Laron syndrome (primary growth hormone insensitivity).

    Science.gov (United States)

    Laron, Zvi

    2008-03-01

    Laron syndrome (LS, congenital primary GH insensitivity) is caused by deletions or mutations in the GH receptor gene, resulting in an inability to generate insulin-like growth factor-I (IGF-I). If untreated, the deficiency of IGF-I results in severe dwarfism, as well as skeletal and muscular underdevelopment. The only treatment is the daily administration of recombinant IGF-I. This review summarizes the present experience by several groups worldwide. The main conclusions are: A. The one or two injections regimen result in the same growth velocity; B. The growth velocity obtained with IGF-I administration is smaller than that observed with hGH in children with congenital isolated GH deficiency; C. Overdosage of IGF-I causes a series of adverse effects which can be avoided by carefully monitoring the serum IGF-I and GH levels.

  10. Clinical and Molecular Features of Laron Syndrome, A Genetic Disorder Protecting from Cancer.

    Science.gov (United States)

    Janecka, Anna; Kołodziej-Rzepa, Marta; Biesaga, Beata

    2016-01-01

    Laron syndrome (LS) is a rare, genetic disorder inherited in an autosomal recessive manner. The disease is caused by mutations of the growth hormone (GH) gene, leading to GH/insulin-like growth factor type 1 (IGF1) signalling pathway defect. Patients with LS have characteristic biochemical features, such as a high serum level of GH and low IGF1 concentration. Laron syndrome was first described by the Israeli physician Zvi Laron in 1966. Globally, around 350 people are affected by this syndrome and there are two large groups living in separate geographic regions: Israel (69 individuals) and Ecuador (90 individuals). They are all characterized by typical appearance such as dwarfism, facial phenotype, obesity and hypogenitalism. Additionally, they suffer from hypoglycemia, hypercholesterolemia and sleep disorders, but surprisingly have a very low cancer risk. Therefore, studies on LS offer a unique opportunity to better understand carcinogenesis and develop new strategies of cancer treatment.

  11. Consequences of not treating children with laron syndrome (primary growth hormone insensitivity).

    Science.gov (United States)

    Laron, Z

    2001-01-01

    The follow-up of a large cohort of patients with Laron syndrome (LS) from infancy to adult age has enabled us to determine the effects of long-term insulin-like growth factor-I (IGF-I) deficiency on auxological, biochemical, physiological and psychological parameters. We found that early and continuous IGF-I deficiency (the anabolic effector of growth hormone) causes dwarfism, acromicria, organomicria, marked obesity, insulin resistance, retardation of skeletal maturation and osteoporosis, as well as muscular and central nervous tissue underdevelopment, and a series of biochemical changes including hypercholesterolemia. These multiple pathologies impair the quality of life of these patients. It is concluded that patients with LS need IGF-I replacement treatment throughout life.

  12. Long-term IGF-I treatment of children with Laron syndrome increases adiposity.

    Science.gov (United States)

    Laron, Zvi; Ginsberg, Shira; Lilos, Pnina; Arbiv, Mira; Vaisman, Nahum

    2006-02-01

    Laron syndrome (LS) is an autosomal recessive disease caused by deletions or mutations in the GH receptor gene leading to an inability of insulin-like growth factor I (IGF-I) generation. Among the major resulting body changes are dwarfism and obesity. The only effective treatment is daily administration of biosynthetic IGF-I. Body composition determination by DEXA (dual energy X-ray absorptiometry) of three girls with LS treated by IGF-I for 1, 3 and 11 1/2 years, respectively, revealed that concomitantly with the increase in growth there was a significant increase in body adipose tissue to double or triple the normal values. Due to the underdevelopment of the muscular and skeletal systems body mass index (BMI) did not accurately reflect the degree of obesity. In conclusion, IGF-I similar to insulin, exerts an adipogenic effect.

  13. Ellis-van Creveld syndrome in an Indian child: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Veena, K.M.; Jagadishchandra, H.; Rao, Prasanna Kumar; Chatra, Laxmikanth [Yenepoya Dental College, Yenepoya University, Mangalore (India)

    2011-12-15

    Ellis-van Creveld syndrome is a rare congenital genetic disorder having autosomal recessive inheritance. It is a syndrome affecting the Amish population of Pennsylvania in USA with prevalence rate of 1/5,000 live at birth. In non-Amish population, the birth prevalence is 7/1,000,000. The syndrome is characterized by bilateral postaxial polydactyly of the hands, chondrodysplasia of long bones resulting in acromesomelic dwarfism, ectodermal dysplasia affecting nails as well as teeth and congenital heart malformation. There were very rare reports of this syndrome in dentistry. The present case focuses on the striking and constant oral findings of these patients, which are the main diagnostic features of this syndrome. Since the oral manifestations affect the esthetic, speech, and jaw growth of the child, the dentists have an important role to play in proper management of such case.

  14. Beneficial effects of anti-growth hormone antiserum in avian muscular dystrophy.

    Science.gov (United States)

    Kurtenbach, E; Moraes, S S; Trocado, M T; Lôbo, G F; Nascimento, P S; Verjovski-Almeida, S

    1989-08-01

    Human subjects and mice have been found to have a milder progression of muscular dystrophy when the disease is associated with genotypically determined dwarfism. In this paper we describe an experimental test for reducing growth hormone in dystrophic chickens that uses rabbit anti-chicken growth hormone anti-serum (anti-cGH). Antiserum was injected daily into dystrophic (line 413) male chickens from day 1 to day 8 after hatching. Dystrophic chickens injected with anti-cGH maintained a significantly higher score in the standardized test for righting ability (P less than 0.001-0.051) from 3 to 9 1/2 wk after hatching when compared with dystrophic controls. The observed prolongation of the functional ability of injected dystrophic animals suggests that growth hormone plays a role in potentiating the symptoms of dystrophy in chickens.

  15. The pleiotropic ABNORMAL FLOWER AND DWARF1 affects plant height, floral development and grain yield in rice

    Science.gov (United States)

    Ren, Deyong; Rao, Yuchun; Wu, Liwen; Xu, Qiankun; Li, Zizhuang; Yu, Haiping; Zhang, Yu; Leng, Yujia; Hu, Jiang; Zhu, Li; Gao, Zhenyu; Dong, Guojun; Zhang, Guangheng; Guo, Longbiao

    2016-01-01

    Abstract Moderate plant height and successful establishment of reproductive organs play pivotal roles in rice grain production. The molecular mechanism that controls the two aspects remains unclear in rice. In the present study, we characterized a rice gene, ABNORMAL FLOWER AND DWARF1 (AFD1) that determined plant height, floral development and grain yield. The afd1 mutant showed variable defects including the dwarfism, long panicle, low seed setting and reduced grain yield. In addition, abnormal floral organs were also observed in the afd1 mutant including slender and thick hulls, and hull‐like lodicules. AFD1 encoded a DUF640 domain protein and was expressed in all tested tissues and organs. Subcellular localization showed AFD1‐green fluorescent fusion protein (GFP) was localized in the nucleus. Meantime, our results suggested that AFD1 regulated the expression of cell division and expansion related genes. PMID:26486996

  16. Research on X-linked growth hormone deficiency and related genes%X连锁隐性遗传性生长激素缺乏症及其相关基因的研究

    Institute of Scientific and Technical Information of China (English)

    王春林; 梁黎

    2013-01-01

    Growth hormone deficiency (GHD) is a common cause of dwarfism.Most GHD patients are sporadic,whilst 5%-30% are of familial type.X-linked GHD patients are relatively rare.We hereby provide a literature review and report on our latest findings on the disease.%生长激素缺乏症(growth hormone deficiency,GHD)是临床常见的导致矮小的疾病.GHD大多散发,约5%~30%呈家族遗传,其中X染色体连锁遗传者(X-linked growth hormone deficiency,XLGHD)较为罕见.我们将系统回顾XLGHD相关致病基因的研究以及最新的发现.

  17. Becker′s nevus syndrome

    Directory of Open Access Journals (Sweden)

    Sathyanarayana B Dasegowda

    2014-01-01

    Full Text Available Becker′s nevus is a cutaneous hamartoma characterized by circumscribed hyperpigmentation with hypertrichosis. Becker′s nevus syndrome is an association of Becker′s nevus with unilateral breast hypoplasia and muscle, skin, and/or skeletal abnormalities. We here report a case of a 15 year-old female who presented with bilateral Becker′s nevus over her groins, thighs, vulva, and in front of the neck from the age of 5 years. She had associated mental retardation, delayed development of mile stones, delayed puberty, dwarfism, depressed nasal bridge, long slender digits, crowding of lateral toes, valgus deformity of first metatarsophalangeal joint, mitral valve prolapse, muddy conjunctiva with hypertrophic and hyperpigmented caruncle of both eyes, ichthyosis, brownish hair, and absence of axillary and pubic hair. On histopathological examination collagen hamartoma underneath the Becker′s nevus was found.

  18. Inhibition of cell proliferation, cell expansion and differentiation by the Arabidopsis SUPERMAN gene in transgenic tobacco plants.

    Science.gov (United States)

    Bereterbide, A; Hernould, M; Castera, S; Mouras, A

    2001-11-01

    Plant development depends upon the control of growth, organization and differentiation of cells derived from shoot and root meristems. Among the genes involved in flower organ determination, the cadastral gene SUPERMAN controls the boundary between whorls 3 and 4 and the growth of the adaxial outer ovule integument by down-regulating cell divisions. To determine the precise function of this gene we overexpressed ectopically the Arabidopsis thaliana (L.) Heynh. SUPERMAN gene in tobacco (Nicotiana tabacum L.). The transgenic plants exhibited a dwarf phenotype. Histologically and cytologically detailed analyses showed that dwarfism is correlated with a reduction in cell number, which is in agreement with the SUPERMAN function in Arabidopsis. Furthermore, a reduction in cell expansion and an impairment of cell differentiation were observed in tobacco organs. These traits were observed in differentiated vegetative and floral organs but not in meristem structures. A potential effect of the SUPERMAN transcription factor in the control of gibberellin biosynthesis is discussed.

  19. Bad bones, absent smell, selfish testes: the pleiotropic consequences of human FGF receptor mutations.

    Science.gov (United States)

    Wilkie, Andrew O M

    2005-04-01

    The discovery in 1994 that highly specific mutations of fibroblast growth factor (FGF) receptor 3 caused the most common form of human short-limbed dwarfism, achondroplasia, heralded a new era in FGF receptor (FGFR) biology. A decade later, the purpose of this review is to survey how the study of humans with FGFR mutations continues to provide insights into FGFR function in health and disease, and the clinical applications of these findings. Amongst the most interesting recent discoveries have been the description of novel phenotypes associated with FGFR1 and FGFR3 mutations; identification of fundamental differences in the cellular mechanisms of mutant FGFR2 and FGFR3 action; and the direct identification of FGFR2 and FGFR3 mutations in sperm. These clinical observations illustrate the pleiotropism of FGFR action and fuel ongoing efforts to understand the rich biology and pathophysiology of the FGF signalling system.

  20. Development of the thyroid gland.

    Science.gov (United States)

    Nilsson, Mikael; Fagman, Henrik

    2017-06-15

    Thyroid hormones are crucial for organismal development and homeostasis. In humans, untreated congenital hypothyroidism due to thyroid agenesis inevitably leads to cretinism, which comprises irreversible brain dysfunction and dwarfism. Elucidating how the thyroid gland - the only source of thyroid hormones in the body - develops is thus key for understanding and treating thyroid dysgenesis, and for generating thyroid cells in vitro that might be used for cell-based therapies. Here, we review the principal mechanisms involved in thyroid organogenesis and functional differentiation, highlighting how the thyroid forerunner evolved from the endostyle in protochordates to the endocrine gland found in vertebrates. New findings on the specification and fate decisions of thyroid progenitors, and the morphogenesis of precursor cells into hormone-producing follicular units, are also discussed. © 2017. Published by The Company of Biologists Ltd.

  1. Molecular and Cellular Basis of Autosomal Recessive Primary Microcephaly

    Directory of Open Access Journals (Sweden)

    Marine Barbelanne

    2014-01-01

    Full Text Available Autosomal recessive primary microcephaly (MCPH is a rare hereditary neurodevelopmental disorder characterized by a marked reduction in brain size and intellectual disability. MCPH is genetically heterogeneous and can exhibit additional clinical features that overlap with related disorders including Seckel syndrome, Meier-Gorlin syndrome, and microcephalic osteodysplastic dwarfism. In this review, we discuss the key proteins mutated in MCPH. To date, MCPH-causing mutations have been identified in twelve different genes, many of which encode proteins that are involved in cell cycle regulation or are present at the centrosome, an organelle crucial for mitotic spindle assembly and cell division. We highlight recent findings on MCPH proteins with regard to their role in cell cycle progression, centrosome function, and early brain development.

  2. Open and closed lip schizencephaly in Seckel syndrome: a case report.

    Science.gov (United States)

    Thapa, Rajoo; Mallick, Debkrishna; Biswas, Biswajit; Ghosh, Apurba

    2010-04-01

    Seckel syndrome (Online Mendelian Inheritance in Man database Number 210600) is the classic prototype of primordial bird-headed dwarfism. In addition to the characteristic craniofacial dysmorphism and skeletal defects, abnormalities of the cardiovascular, hematopoietic, endocrine, and central nervous systems are described. The full phenotypic spectrum of this clinically and genetically heterogeneous syndrome is yet to be delineated. Presented herein is a boy 2 years and 5 months old, with Seckel syndrome, born to second-degree consanguineous Muslim parents. In addition to the classic phenotype of the disorder, this patient had both, an open and a closed lip schizencephaly detected on cranial computed tomography (CT) scan. To our knowledge, the association of schizencephaly and Seckel syndrome is not described previously in the English language literature. In addition, presented briefly is a review of the anatomical cerebral cortical malformations associated with this syndrome.

  3. The gene for the Ellis-van Creveld syndrome is located on chromosome 4p16

    Energy Technology Data Exchange (ETDEWEB)

    Polymeropoulos, M.H.; Ide, S.E. [National Institute of Health, Bethesda, MD (United States); Wright, M. [Univ. of Newcastle Upon Tyne (United Kingdom)] [and others

    1996-07-01

    Ellis-van Creveld syndrome (EVC) is an autosomal recessive disorder characterized by disproportionate dwarfism, polydactyly, and congenital heart disease. This rare disorder is found with increased frequency among the Old Order Amish community in Lancaster County, Pennsylvania. We have used linkage analysis to localize the gene responsible for the EVC phenotype in nine interrelated Amish pedigrees and three unrelated families from Mexico, Ecuador, and Brazil. We now report the linkage for the Ellisvan Creveld syndrome gene to markers on the distal short arm of human chromosome 4, with Z{sub max} = 6.91 at {theta} = 0.02 for marker HOX7, in a region proximal to the FGFR3 gene responsible for the achondroplasia phenotype. 17 refs., 2 figs., 1 tab.

  4. A common FGFR3 gene mutation is present in achondroplasia but not in hypochondroplasia

    Energy Technology Data Exchange (ETDEWEB)

    Stoilov, I.; Kilpatrick, M.W.; Tsipouras, P. [Univ. of Connecticut Health Center, Farmington, CT (United States)

    1995-01-02

    Achondroplasia is the most common type of genetic dwarfism. It is characterized by disproportionate short stature and other skeletal anomalies resulting from a defect in the maturation of the chondrocytes in the growth plate of the cartilage. Recent studies mapped the achondroplasia gene on chromosome region 4p16.3 and identified a common mutation in the gene encoding the fibroblast growth factor receptor 3 (FGFR3). In an analysis of 19 achondroplasia families from a variety of ethnic backgrounds we confirmed the presence of the G380R mutation in 21 of 23 achondroplasia chromosomes studied. In contrast, the G380R mutation was not found in any of the 8 hypochondroplasia chromosomes studied. Futhermore, linkage studies in a 3-generation family with hypochondroplasia show discordant segregation with markers in the 4p16.3 region suggesting that at least some cases of hypochondroplasia are caused by mutations in a gene other than FGFR3. 27 refs., 2 figs.

  5. Genetic linkage of mild pseudoachondroplasia (PSACH) to markers in the pericentromeric region of chromosome 19

    Energy Technology Data Exchange (ETDEWEB)

    Briggs, M.D.; Rasmussen, M.; Garber, P.; Rimoin, D.L.; Cohn, D.H. (Steven Spielberg Pediatric Research Center, Los Angeles, CA (United States)); Weber, J.L. (Marshfield Medical Research Foundation, WI (United States)); Yuen, J.; Reinker, K. (Univ. of Hawaii, Honolulu, HI (United States))

    1993-12-01

    Pseudoachondroplasia (PSACH) is a dominantly inherited form of short-limb dwarfism characterized by dysplastic changes in the spine, epiphyses, and metaphyses and early onset osteoarthropathy. Chondrocytes from affected individuals accumulate an unusual appearing material in the rough endoplasmic reticulum, which has led to the hypothesis that a structural abnormality in a cartilage-specific protein produces the phenotype. The authors recently identified a large family with a mild form of pseudoachondroplasia. By genetic linkage to a dinucleotide repeat polymorphic marker (D19S199), they have localized the disease gene to chromosome 19 (maximum lod score of 7.09 at a recombination fraction of 0.03). Analysis of additional markers and recombinations between the linked markers and the phenotype suggests that the disease gene resides within a 6.3-cM interval in the immediate pericentromeric region of the chromosome. 39 refs., 2 figs., 1 tab.

  6. Case report 512: Spondyloenchondrodysplasia (SED) in two siblings

    Energy Technology Data Exchange (ETDEWEB)

    Ziv, N.; Grunebaum, M.; Kornreich, L.; Mimouni, M.

    1989-01-01

    A pair of siblings are presented with the diagnosis of spondyloenchondrodysplasia (SED) as a disorder in which the chondrocytes in the various growth plates of the long bones and in certain primary ossification centers (vertebral body) fail to mature. Typical features of enchondromatosis are noted. In addition, the spine shows platyspondyly and vertical radiolucent linear clefts just adjacent to the posterior margins of the vertebral bodies. A 'bubbly' appearance is noted in the posterior aspects of the vertebral bodies with irregular sclerotic end plates and a tongue-like configuration of their anterior borders. All laboratory data were normal. The two children may be compared with Schorr's two children reported in 1976 with similar findings. Some degree of dwarfism exists in the children. The tabular summary of the case reported in this article and the two cases of Schorr are appended.

  7. Characterization of a gene from the EDM1-PSACH region of human chromosome 19p

    Energy Technology Data Exchange (ETDEWEB)

    Lennon, G.G.; Giorgi, D.; Martin, J.R. [Lawrence Livermore National Lab., CA (United States)] [and others

    1994-09-01

    Genetic linkage mapping has indicated that both multiple epiphyseal dysplasia (EDM1), a dominantly inherited chondrodysplasia, and pseudoachondroplasia (PSACH), a skeletal disorder associated with dwarfism, map to a 2-3 Mb region of human chromosome 19p. We have isolated a partial cDNA from this region using hybrid selection, and report on progress towards the characterization of the genomic structure and transcription of the corresponding gene. Sequence analysis of the cDNA to date indicates that this gene is likely to be expressed within extracellular matrix tissues. Defects in this gene or neighboring gene family members may therefore lead to EDM1, PSACH, or other connective tissue and skeletal disorders.

  8. Thanatophoric dysplasia: Antenatal to postmortem

    Directory of Open Access Journals (Sweden)

    Chanabasappa V Chavadi

    2015-01-01

    Full Text Available Thanatophoric dwarfism (TD, literally meaning death seeking dwarf, is the most common form of lethal bone dysplasia characterized by severe micromelia, extra folds of skin and narrow chest. Other signs include small ribs, underdeveloped lungs, cloverleaf skull, hypertelorism and protuberant abdomen. A short neck, depressed nasal bridge and hypoplastic mandible may also be present. Hydrocephalus is uncommon but is another poor prognostic sign. The diagnosis is usually made with the ultrasonography in the second trimester. Based on the morphological characters, this condition is sub-divided into type 1 and type 2. Fetuses with this condition are either still-born or die shortly after birth. Antenatal sonographic, postpartum radiological and autopsy findings of a case of type 1 TD with a relatively uncommon association of hydrocephalus is discussed.

  9. Concomitant achondroplasia and developmental dysplasia of the hip

    Directory of Open Access Journals (Sweden)

    Tennison L. Malcolm, MD

    2015-12-01

    Full Text Available Achondroplasia (ACH is the most common form of hereditary dwarfism and presents with multiple musculoskeletal anomalies but is not normally associated with premature hip arthritis. Developmental dysplasia of the hip (DDH is a spectrum of disease resulting in shallow acetabular depth and a propensity for chronic femoral subluxation or dislocation; it is among the most common causes of premature arthritis. This case report describes the diagnosis of symptomatic DDH in a patient with ACH and highlights difficulties of primary total hip arthroplasty (THA as a treatment option. Intraoperative radiographic imaging is advised to ensure proper prosthesis placement. Femoral osteotomy may aid visualization, reduction, and avoidance of soft tissue injury. Concomitant ACH and DDH is a challenging problem that can be successfully treated with modified THA.

  10. Ellis-van Creveld Syndrome: A Case Report of Two Brothers

    Directory of Open Access Journals (Sweden)

    Tibin K Baby

    2016-01-01

    Full Text Available Ellis-van Creveld (EVC syndrome is a rare genetic disorder with autosomal recessive transmission, clinically presenting as bilateral postaxial polydactyly, chondrodysplasia of long bones resulting in acromesomelic dwarfism and ectodermal dysplasia. Mutation in EVC1 and EVC2 gene located in a head to head configuration on chromosome 4p16 has been associ - ated with this syndrome. In Amish community of Pennsylvania, EVC prevalence rate is 1/5,000 and, in non-Amish population, the birth prevalence is 7/1,000,000. Prenatal abnormalities include narrow thorax, shortening of long bones, hexadactyly and cardiac defects. Heart defects, especially atrial septation defects, occur in about 60% of cases. Cognitive and motor development is quite normal. The oral manifestations include upper labiogingival fusion, partial harelip, conical teeth, enamel hypoplasia, hypodontia and neonatal teeth. This case report focuses on striking oral findings and main diagnostic features of this syndrome.

  11. Pre-mRNA splicing in disease and therapeutics.

    Science.gov (United States)

    Singh, Ravi K; Cooper, Thomas A

    2012-08-01

    In metazoans, alternative splicing of genes is essential for regulating gene expression and contributing to functional complexity. Computational predictions, comparative genomics, and transcriptome profiling of normal and diseased tissues indicate that an unexpectedly high fraction of diseases are caused by mutations that alter splicing. Mutations in cis elements cause missplicing of genes that alter gene function and contribute to disease pathology. Mutations of core spliceosomal factors are associated with hematolymphoid neoplasias, retinitis pigmentosa, and microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1). Mutations in the trans regulatory factors that control alternative splicing are associated with autism spectrum disorder, amyotrophic lateral sclerosis (ALS), and various cancers. In addition to discussing the disorders caused by these mutations, this review summarizes therapeutic approaches that have emerged to correct splicing of individual genes or target the splicing machinery.

  12. Ellis-Van Creveld Syndrome: Report of a Family with 3 Cases

    Directory of Open Access Journals (Sweden)

    Mahyar Mohammadi Fard

    2009-01-01

    Full Text Available "nEllis-van Creveld Syndrome (EVC is a rare inherited genetic disorder characterized by polydactyly (extra fingers and toes, dwarfism, and abnormalities in the heart, teeth, nails, and hair. The incidence of EVC is extremely rare in the general population. It is estimated that EVC affects one in 60,000 live births in the general United States population and are much lower in European countries, with one child born with EVC in every 150,000 live births. "nHerein we present three cases of EVC syndrome in one family (An 8-year-old boy and his sisters, two 11 and 6-year-old girls who were admitted to Birjand Imam Reza hospital complaining of short stature. The clinical findings in the physical examination are explained and the role of plain X-rays, echocardiography and cardiac angiography in the diagnosis and management of the anomalies are discussed in these rare 3 cases.  

  13. Ichthyosis vulgaris and pycnodysostosis: An unusual occurrence

    Directory of Open Access Journals (Sweden)

    Vinayak Y. Kshirsagar

    2012-11-01

    Full Text Available Pycnodysostosis is a rare autosomal recessive disorder whose generesponsible for this phenotype (CTSK, mapped to human chromosome1q21, code for the enzyme cathepsin K, a lysosomal cysteineprotease; with an estimated incidence of 1.7 per 1 million births. This clinical entity includes micromelic dwarfism, increased radiological bone density, dysplasia of the skull, acro-osteolysis, straightening of the mandibular angle and in some cases, dysplasia of the acromial end of the clavicle. Oral and maxillo-facial manifestations of this disease are very clear. Herein we reported a case of pycnodysostosis, showing short stature with widening of the sutures, unfused anterior and posterior fontanelles, crowding of teeth with dental caries and typical radiological features associated with ichthyosis vulgaris and palmoplantar keratoderma.

  14. Dexamethasone stimulates expression of C-type Natriuretic Peptide in chondrocytes

    Directory of Open Access Journals (Sweden)

    Beier Frank

    2006-11-01

    Full Text Available Abstract Background Growth of endochondral bones is regulated through the activity of cartilaginous growth plates. Disruption of the physiological patterns of chondrocyte proliferation and differentiation – such as in endocrine disorders or in many different genetic diseases (e.g. chondrodysplasias – generally results in dwarfism and skeletal defects. For example, glucocorticoid administration in children inhibits endochondral bone growth, but the molecular targets of these hormones in chondrocytes remain largely unknown. In contrast, recent studies have shown that C-type Natriuretic Peptide (CNP is an important anabolic regulator of cartilage growth, and loss-of-function mutations in the human CNP receptor gene cause dwarfism. We asked whether glucocorticoids could exert their activities by interfering with the expression of CNP or its downstream signaling components. Methods Primary mouse chondrocytes in monolayer where incubated with the synthetic glucocorticoid Dexamethasone (DEX for 12 to 72 hours. Cell numbers were determined by counting, and real-time PCR was performed to examine regulation of genes in the CNP signaling pathway by DEX. Results We show that DEX does influence expression of key genes in the CNP pathway. Most importantly, DEX significantly increases RNA expression of the gene encoding CNP itself (Nppc. In addition, DEX stimulates expression of Prkg2 (encoding cGMP-dependent protein kinase II and Npr3 (natriuretic peptide decoy receptor genes. Conversely, DEX was found to down-regulate the expression of the gene encoding its receptor, Nr3c1 (glucocorticoid receptor, as well as the Npr2 gene (encoding the CNP receptor. Conclusion Our data suggest that the growth-suppressive activities of DEX are not due to blockade of CNP signaling. This study reveals a novel, unanticipated relationship between glucocorticoid and CNP signaling and provides the first evidence that CNP expression in chondrocytes is regulated by endocrine

  15. Isolation and characterisation of a dwarf rice mutant exhibiting defective gibberellins biosynthesis.

    Science.gov (United States)

    Ji, S H; Gururani, M A; Lee, J W; Ahn, B-O; Chun, S-C

    2014-03-01

    We have isolated a severe dwarf mutant derived from a Ds (Dissociation) insertion mutant rice (Oryza sativa var. japonica c.v. Dongjin). This severe dwarf phenotype, has short and dark green leaves, reduced shoot growth early in the seedling stage, and later severe dwarfism with failure to initiate flowering. When treated with bioactive GA3 , mutants are restored to the normal wild-type phenotype. Reverse transcription PCR analyses of 22 candidate genes related to the gibberellin (GA) biosynthesis pathway revealed that among 22 candidate genes tested, a dwarf mutant transcript was not expressed only in one OsKS2 gene. Genetic analysis revealed that the severe dwarf phenotype was controlled by recessive mutation of a single nuclear gene. The putative OsKS2 gene was a chromosome 4-located ent-kaurene synthase (KS), encoding the enzyme that catalyses an early step of the GA biosynthesis pathway. Sequence analysis revealed that osks2 carried a 1-bp deletion in the ORF region of OsKS2, which led to a loss-of-function mutation. The expression pattern of OsKS2 in wild-type cv Dongjin, showed that it is expressed in all organs, most prominently in the stem and floral organs. Morphological characteristics of the dwarf mutant showed dramatic modifications in internal structure and external morphology. We propose that dwarfism in this mutant is caused by a point mutation in OsKS2, which plays a significant role in growth and development of higher plants. Further investigation on OsKS2 and other OsKS-like proteins is underway and may yield better understanding of the putative role of OsKS in severe dwarf mutants.

  16. A semidwarf phenotype of barley uzu results from a nucleotide substitution in the gene encoding a putative brassinosteroid receptor.

    Science.gov (United States)

    Chono, Makiko; Honda, Ichiro; Zeniya, Haruko; Yoneyama, Koichi; Saisho, Daisuke; Takeda, Kazuyoshi; Takatsuto, Suguru; Hoshino, Tsuguhiro; Watanabe, Yoshiaki

    2003-11-01

    Brassinosteroids (BRs) play important roles throughout plant growth and development. Despite the importance of clarifying the mechanism of BR-related growth regulation in cereal crops, BR-related cereal mutants have been identified only in rice (Oryza sativa). We previously found that semidwarf barley (Hordeum vulgare) accessions carrying the "uzu" gene, called "uzu" barley in Japan, are non-responding for brassinolide (BL). We then performed chemical and molecular analyses to clarify the mechanisms of uzu dwarfism using isogenic line pairs of uzu gene. The response of the uzu line to BL was significantly lower than that of its corresponding normal line. Measurement of BRs showed that the uzu line accumulates BRs, similar to known BR-insensitive mutants. The marker synteny of rice and barley chromosomes suggests that the uzu gene may be homologous to rice D61, a rice homolog of Arabidopsis BR-insensitive 1 (BRI1), encoding a BR-receptor protein. A barley homolog of BRI1, HvBRI1, was isolated by using degenerate primers. A comparison of HvBRI1 sequences in uzu and normal barley varieties showed that the uzu phenotype is correlated with a single nucleotide substitution. This substitution results in an amino acid change at a highly conserved residue in the kinase domain of the BR-receptor protein. These results may indicate that uzu dwarfism is caused by the missense mutation in HvBRI1. The uzu gene is being introduced into all hull-less barley cultivars in Japan as an effective dwarf gene for practical use, and this is the first report about an agronomically important mutation related to BRs.

  17. Nuclear isoforms of fibroblast growth factor 2 are novel inducers of hypophosphatemia via modulation of FGF23 and KLOTHO.

    Science.gov (United States)

    Xiao, Liping; Naganawa, Takahiro; Lorenzo, Joseph; Carpenter, Thomas O; Coffin, J Douglas; Hurley, Marja M

    2010-01-22

    FGF2 transgenic mice were developed in which type I collagen regulatory sequences drive the nuclear high molecular weight FGF2 isoforms in osteoblasts (TgHMW). The phenotype of TgHMW mice included dwarfism, decreased bone mineral density (BMD), osteomalacia, and decreased serum phosphate (P(i)). When TgHMW mice were fed a high P(i) diet, BMD was increased, and dwarfism was partially reversed. The TgHMW phenotype was similar to mice overexpressing FGF23. Serum FGF23 was increased in TgHMW mice. Fgf23 mRNA in bones and fibroblast growth factor receptors 1c and 3c and Klotho mRNAs in kidneys were increased in TgHMW mice, whereas the renal Na(+)/P(i) co-transporter Npt2a mRNA was decreased. Immunohistochemistry and Western blot analyses of TgHMW kidneys showed increased KLOTHO and decreased NPT2a protein. The results suggest that overexpression of HMW FGF2 increases FGF23/FGFR/KLOTHO signaling to down-regulate NPT2a, causing P(i) wasting, osteomalacia, and decreased BMD. We assessed whether HMW FGF2 expression was altered in the Hyp mouse, a mouse homolog of the human disease X-linked hypophosphatemic rickets/osteomalacia. Fgf2 mRNA was increased in bones, and Western blots showed increased FGF2 protein in nuclear fractions from osteoblasts of Hyp mice. In addition, immunohistochemistry demonstrated co-localization of FGF23 and HMW FGF2 protein in osteoblasts and osteocytes from Hyp mice. This study reveals a novel mechanism of regulation of the FGF23-P(i) homeostatic axis.

  18. Impact of trace metal concentrations on coccolithophore growth and morphology: laboratory simulations of Cretaceous stress

    Directory of Open Access Journals (Sweden)

    G. Faucher

    2017-07-01

    Full Text Available The Cretaceous ocean witnessed intervals of profound perturbations such as volcanic input of large amounts of CO2, anoxia, eutrophication and introduction of biologically relevant metals. Some of these extreme events were characterized by size reduction and/or morphological changes of a few calcareous nannofossil species. The correspondence between intervals of high trace metal concentrations and coccolith dwarfism suggests a negative effect of these elements on nannoplankton biocalcification processes in past oceans. In order to test this hypothesis, we explored the potential effect of a mixture of trace metals on growth and morphology of four living coccolithophore species, namely Emiliania huxleyi, Gephyrocapsa oceanica, Pleurochrysis carterae and Coccolithus pelagicus. The phylogenetic history of coccolithophores shows that the selected living species are linked to Mesozoic species showing dwarfism under excess metal concentrations. The trace metals tested were chosen to simulate the environmental stress identified in the geological record and upon known trace metal interactions with living coccolithophore algae.Our laboratory experiments demonstrated that elevated trace metal concentrations, similarly to the fossil record, affect coccolithophore algae size and/or weight. Smaller coccoliths were detected in E. huxleyi and C. pelagicus, while coccoliths of G. oceanica showed a decrease in size only at the highest trace metal concentrations. P. carterae coccolith size was unresponsive to changing trace metal concentrations. These differences among species allow discriminating the most- (P. carterae, intermediate- (E. huxleyi and G. oceanica and least-tolerant (C. pelagicus taxa. The fossil record and the experimental results converge on a selective response of coccolithophores to metal availability.These species-specific differences must be considered before morphological features of coccoliths are used to reconstruct paleo-chemical conditions.

  19. Inheritance and identification of molecular markers associated with a novel dwarfing gene in barley

    Directory of Open Access Journals (Sweden)

    Sun Genlou

    2010-10-01

    Full Text Available Abstract Background Dwarfing genes have widely been used in barley breeding program. More than 30 types of dwarfs or semidwarfs have been reported, but a few has been exploited in barley breeding because pleiotropic effects of dwarfing genes cause some undesired traits. The plant architecture of newly discovered dwarfing germplasm "Huaai 11" consisted of desirable agronomic traits such as shortened stature and early maturity. Genetic factor controlling the plant height in dwarf line Huaai 11 was investigated. Results The Huaai 11 was crossed with tall varieties Monker, Mpyt, Zhenongda 3, Zaoshu 3, Advance, Huadamai 1, Huadamai 6, Hyproly and Ris01508. All the F1 plants displayed tall trait. Both tall and dwarf plants appeared in all the F2 populations with a 3:1 segregation ratio, suggesting that dwarfism of Huaai 11 is controlled by a single recessive gene, btwd1. Allelism test indicated that this dwarfing gene in the Huaai 11 is nonallelic with the gene br, uzu, sdw1 and denso. Using a double haploid population derived from a cross of Huadamai 6 and Huaai 11 and SSR markers the novel dwarfing gene was mapped onto the long arm of chromosome 7H, and closely linked to Bmac031 and Bmac167 with genetic distance of 2.2 cM. Conclusion Huaai 11 is a new source of dwarf for broadening the genetic base of dwarfism. This dwarf source was controlled by a recessive dwarfing gene btwd1, was mapped onto the long arm of chromosome 7H.

  20. Impact of trace metal concentrations on coccolithophore growth and morphology: laboratory simulations of Cretaceous stress

    Science.gov (United States)

    Faucher, Giulia; Hoffmann, Linn; Bach, Lennart T.; Bottini, Cinzia; Erba, Elisabetta; Riebesell, Ulf

    2017-07-01

    The Cretaceous ocean witnessed intervals of profound perturbations such as volcanic input of large amounts of CO2, anoxia, eutrophication and introduction of biologically relevant metals. Some of these extreme events were characterized by size reduction and/or morphological changes of a few calcareous nannofossil species. The correspondence between intervals of high trace metal concentrations and coccolith dwarfism suggests a negative effect of these elements on nannoplankton biocalcification processes in past oceans. In order to test this hypothesis, we explored the potential effect of a mixture of trace metals on growth and morphology of four living coccolithophore species, namely Emiliania huxleyi, Gephyrocapsa oceanica, Pleurochrysis carterae and Coccolithus pelagicus. The phylogenetic history of coccolithophores shows that the selected living species are linked to Mesozoic species showing dwarfism under excess metal concentrations. The trace metals tested were chosen to simulate the environmental stress identified in the geological record and upon known trace metal interactions with living coccolithophore algae.Our laboratory experiments demonstrated that elevated trace metal concentrations, similarly to the fossil record, affect coccolithophore algae size and/or weight. Smaller coccoliths were detected in E. huxleyi and C. pelagicus, while coccoliths of G. oceanica showed a decrease in size only at the highest trace metal concentrations. P. carterae coccolith size was unresponsive to changing trace metal concentrations. These differences among species allow discriminating the most- (P. carterae), intermediate- (E. huxleyi and G. oceanica) and least-tolerant (C. pelagicus) taxa. The fossil record and the experimental results converge on a selective response of coccolithophores to metal availability.These species-specific differences must be considered before morphological features of coccoliths are used to reconstruct paleo-chemical conditions.

  1. Changes in coccolith sizes through Oceanic Anoxic Event 2: a proxy of ocean acidification?

    Science.gov (United States)

    Faucher, Giulia; Erba, Elisabetta

    2013-04-01

    results were compared to the morphometric data collected through OAE1a. During OAE1a dwarfism and malformation are restricted to the C isotopic negative shift and most profound paleoenvironmental perturbations. In the OAE2 interval dwarfism is most pronounced in the last part of the C isotopic anomaly, and coccolith malformation is negligible. Based on available data, climatic and fertility changes per se appear to be of marginal relevance to coccolith morphologies. In particular, the nannofossil record of paleo-fertility during OAE2 is not straightforward, since increases or decreases in abundance were documented in different settings. Similarly to OAE1a, we speculate that during OAE2, excess CO2 played a fundamental role in nannoplankton calcification, and that coccolith dwarfism might be a proxy of ocean acidification. In the analyzed sections, during OAE2, dwarf coccoliths occur at levels with metal peaks, perhaps also-alternatively recording a species-specific intolerance to metal toxicity.

  2. Changes in calcareous nannoplankton calcification during the latest Cenomanian Oceanic Anoxic Event 2 and similarity with other Cretaceous Oceanic Anoxic Events

    Science.gov (United States)

    Faucher, Giulia; Erba, Elisabetta; Bottini, Cinzia

    2016-04-01

    The Cenomanian has been characterized by greenhouse climate conditions and profound environmental perturbations, including the latest Cenomanian Oceanic Anoxic Event 2 (OAE 2), an episode of widespread organic matter burial in oxygen-depleted oceans. OAE 2 is thought to be related to the emplacement of the Caribbean Plateau which probably introduced in the atmosphere a large amount of CO2 with consequent impact on biota, climate and ocean chemistry. The perturbation of the carbon cycle is reflected in the carbon isotopic record that evidences a positive shift at the OAE 2 onset and subsequent C-isotopic peaks. The aim of this study is the identification of possible changes in coccolith size/shape as a response to paleoenvironmental perturbations associated with OAE 2. Biometric analyses were performed on selected coccolith species (Biscutum constans, Discorhabdus rotatorius, Watznaueria barnesiae and Zeugrabdothus erectus) from five sections spanning the Cenomanian-Turonian boundary interval including OAE 2. The study provided evidence for size fluctuations and dwarfism of B. constans, Z. erectus and D. rotatorius during OAE 2, followed by a recovery at the end of the event. On the contrary, W. barnesiae displays constant sizes through the event. High-resolution investigations showed that B. constans follows the same size trends in all the analysed sections with i) a decrease in size at the OAE 2 onset where an increase in pCO2 is observed, ii) a partial increase in size back to pre-OAE 2 values around the first δ13C peak (peak A), where a decrease in pCO2 concentration is reconstructed iii) and a subsequent more expressed decrease in size reaching minimum values around the δ13C peak B where trace metal abundance has been identified. Small specimens are present till the end of OAE 2 and only after δ13C peak D a partial recovery in size is observed. Nannoplankton dwarfism is here interpreted as forced by rapidly increasing pCO2 during the formation of the

  3. Body size evolution in insular speckled rattlesnakes (Viperidae: Crotalus mitchellii).

    Science.gov (United States)

    Meik, Jesse M; Lawing, A Michelle; Pires-daSilva, André

    2010-03-04

    Speckled rattlesnakes (Crotalus mitchellii) inhabit multiple islands off the coast of Baja California, Mexico. Two of the 14 known insular populations have been recognized as subspecies based primarily on body size divergence from putative mainland ancestral populations; however, a survey of body size variation from other islands occupied by these snakes has not been previously reported. We examined body size variation between island and mainland speckled rattlesnakes, and the relationship between body size and various island physical variables among 12 island populations. We also examined relative head size among giant, dwarfed, and mainland speckled rattlesnakes to determine whether allometric differences conformed to predictions of gape size (and indirectly body size) evolving in response to shifts in prey size. Insular speckled rattlesnakes show considerable variation in body size when compared to mainland source subspecies. In addition to previously known instances of gigantism on Angel de la Guarda and dwarfism on El Muerto, various degrees of body size decrease have occurred frequently in this taxon, with dwarfed rattlesnakes occurring mostly on small, recently isolated, land-bridge islands. Regression models using the Akaike information criterion (AIC) showed that mean SVL of insular populations was most strongly correlated with island area, suggesting the influence of selection for different body size optima for islands of different size. Allometric differences in head size of giant and dwarf rattlesnakes revealed patterns consistent with shifts to larger and smaller prey, respectively. Our data provide the first example of a clear relationship between body size and island area in a squamate reptile species; among vertebrates this pattern has been previously documented in few insular mammals. This finding suggests that selection for body size is influenced by changes in community dynamics that are related to graded differences in area over what are

  4. Identifying quantitative trait loci affecting resistance to congenital hypothyroidism in 129/SvJcl strain mice.

    Directory of Open Access Journals (Sweden)

    Yayoi Hosoda

    Full Text Available Tyrosylprotein sulfotransferase 2 (TPST2 is one of the enzymes responsible for tyrosine O-sulfation and catalyzes the sulfation of the specific tyrosine residue of thyroid stimulating hormone receptor (TSHR. Since this modification is indispensable for the activation of TSH signaling, a non-functional TPST2 mutation (Tpst2(grt in DW/J-grt mice leads to congenital hypothyroidism (CH characterized by severe thyroid hypoplasia and dwarfism related to TSH hyporesponsiveness. Previous studies indicated that the genetic background of the 129(+Ter/SvJcl (129 mouse strain ameliorates Tpst2(grt-induced CH. To identify loci responsible for CH resistance in 129 mice, we performed quantitative trait locus (QTL analysis using backcross progenies from susceptible DW/J and resistant 129 mice. We used the first principal component calculated from body weights at 5, 8 and 10 weeks as an indicator of CH, and QTL analysis mapped a major QTL showing a highly significant linkage to the distal portion of chromosome (Chr 2; between D2Mit62 and D2Mit304, particularly close to D2Mit255. In addition, two male-specific QTLs showing statistically suggestive linkage were also detected on Chrs 4 and 18, respectively. All QTL alleles derived from the 129 strain increased resistance to growth retardation. There was also a positive correlation between recovery from thyroid hypoplasia and the presence of the 129 allele at D2Mit255 in male progenies. These results suggested that the major QTL on Chr 2 is involved in thyroid development. Moreover, since DW/J congenic strain mice carrying both a Tpst2(grt mutation and 129 alleles in the major QTL show resistance to dwarfism and thyroid hypoplasia, we confirmed the presence of the resistant gene in this region, and that it is involved in thyroid development. Further genetical analysis should lead to identification of genes for CH tolerance and, from a better understanding of thyroid organogenesis and function, the subsequent

  5. Body size evolution in insular speckled rattlesnakes (Viperidae: Crotalus mitchellii.

    Directory of Open Access Journals (Sweden)

    Jesse M Meik

    Full Text Available BACKGROUND: Speckled rattlesnakes (Crotalus mitchellii inhabit multiple islands off the coast of Baja California, Mexico. Two of the 14 known insular populations have been recognized as subspecies based primarily on body size divergence from putative mainland ancestral populations; however, a survey of body size variation from other islands occupied by these snakes has not been previously reported. We examined body size variation between island and mainland speckled rattlesnakes, and the relationship between body size and various island physical variables among 12 island populations. We also examined relative head size among giant, dwarfed, and mainland speckled rattlesnakes to determine whether allometric differences conformed to predictions of gape size (and indirectly body size evolving in response to shifts in prey size. METHODOLOGY/PRINCIPAL FINDINGS: Insular speckled rattlesnakes show considerable variation in body size when compared to mainland source subspecies. In addition to previously known instances of gigantism on Angel de la Guarda and dwarfism on El Muerto, various degrees of body size decrease have occurred frequently in this taxon, with dwarfed rattlesnakes occurring mostly on small, recently isolated, land-bridge islands. Regression models using the Akaike information criterion (AIC showed that mean SVL of insular populations was most strongly correlated with island area, suggesting the influence of selection for different body size optima for islands of different size. Allometric differences in head size of giant and dwarf rattlesnakes revealed patterns consistent with shifts to larger and smaller prey, respectively. CONCLUSIONS/SIGNIFICANCE: Our data provide the first example of a clear relationship between body size and island area in a squamate reptile species; among vertebrates this pattern has been previously documented in few insular mammals. This finding suggests that selection for body size is influenced by changes in

  6. XBP1-Independent UPR Pathways Suppress C/EBP-β Mediated Chondrocyte Differentiation in ER-Stress Related Skeletal Disease.

    Directory of Open Access Journals (Sweden)

    Trevor L Cameron

    2015-09-01

    Full Text Available Schmid metaphyseal chondrodysplasia (MCDS involves dwarfism and growth plate cartilage hypertrophic zone expansion resulting from dominant mutations in the hypertrophic zone collagen, Col10a1. Mouse models phenocopying MCDS through the expression of an exogenous misfolding protein in the endoplasmic reticulum (ER in hypertrophic chondrocytes have demonstrated the central importance of ER stress in the pathology of MCDS. The resultant unfolded protein response (UPR in affected chondrocytes involved activation of canonical ER stress sensors, IRE1, ATF6, and PERK with the downstream effect of disrupted chondrocyte differentiation. Here, we investigated the role of the highly conserved IRE1/XBP1 pathway in the pathology of MCDS. Mice with a MCDS collagen X p.N617K knock-in mutation (ColXN617K were crossed with mice in which Xbp1 was inactivated specifically in cartilage (Xbp1CartΔEx2, generating the compound mutant, C/X. The severity of dwarfism and hypertrophic zone expansion in C/X did not differ significantly from ColXN617K, revealing surprising redundancy for the IRE1/XBP1 UPR pathway in the pathology of MCDS. Transcriptomic analyses of hypertrophic zone cartilage identified differentially expressed gene cohorts in MCDS that are pathologically relevant (XBP1-independent or pathologically redundant (XBP1-dependent. XBP1-independent gene expression changes included large-scale transcriptional attenuation of genes encoding secreted proteins and disrupted differentiation from proliferative to hypertrophic chondrocytes. Moreover, these changes were consistent with disruption of C/EBP-β, a master regulator of chondrocyte differentiation, by CHOP, a transcription factor downstream of PERK that inhibits C/EBP proteins, and down-regulation of C/EBP-β transcriptional co-factors, GADD45-β and RUNX2. Thus we propose that the pathology of MCDS is underpinned by XBP1 independent UPR-induced dysregulation of C/EBP-β-mediated chondrocyte differentiation

  7. Evolution and Production of Calcareous Nannoplankton During the Cretaceous as Proxies of LIP-induced Oceanic Fertilization, Acidification and Anoxia

    Science.gov (United States)

    Erba, E.; Bottini, C.; Tiraboschi, D.

    2008-12-01

    Through the Phanerozoic, biota have been intimately linked to Earth's degassing inducing major changes in composition and structure of the ocean-atmosphere system. Emplacement of large igneous provinces (LIPs) has been the primary natural source of atmCO2 with dramatic consequences on climate and ecosystems. During the mid-Cretaceous the Ontong Java-Manihiki and Caribbean Plateaus LIPs are recognized as responsible of pCO2 as high as 2000 ppm. Coeval biocalcification crises occurred in pelagic and neritic settings, suggesting a causal link between high concentrations of carbon dioxide and drops in benthic and planktonic calcifiers' efficiency. Within the oceanic biosphere, calcareous nannoplankton play a key-role as: (1) is widespread and consists of cosmopolitan and endemic taxa; (2) has a 220 My-long evolutionary history; (3) is one the most effective calcite producers; (4) is relevant for the C cycle; (5) is extremely sensitive to environmental variations. Diversity pulses of Cretaceous calcareous nannoplankton are grossly coeval with LIP construction, climate and sea-level changes, variations in ocean structure and composition, suggesting that evolutionary patterns are closely linked to environmental modifications. We explored time-intervals of LIP formation marked by nannoplankton adaptation/evolution, quantifying evolutionary rates, species richness, abundance, calcite production and morphometry. High-resolution investigations of the initial phase of both early Aptian oceanic anoxic event (OAE) 1a and latest Cenomanian OAE 2 pointed out major evolutionary changes, decreases in heavily calcified nannoliths and occurrence of dwarf coccoliths. Nannoplankton calcification crises and dwarfism is here interpreted as forced by rapidly increasing pCO2 during formation of the Ontong Java-Maniniki and Caribbean Plateaus. Alternatively or concurrently, calcification crash and dwarfism might result from enhanced fertility associated to OAE1a and OAE2 regardless of ocean

  8. The BAH domain of ORC1 links H4K20me2 to DNA replication licensing and Meier-Gorlin syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kuo, Alex J; Song, Jikui; Cheung, Peggie; Ishibe-Murakami, Satoko; Yamazoe, Sayumi; Chen, James K; Patel, Dinshaw J; Gozani, Or [Stanford; (MSKCC); (Stanford-MED)

    2012-07-11

    The recognition of distinctly modified histones by specialized 'effector' proteins constitutes a key mechanism for transducing molecular events at chromatin to biological outcomes. Effector proteins influence DNA-templated processes, including transcription, DNA recombination and DNA repair; however, no effector functions have yet been identified within the mammalian machinery that regulate DNA replication. Here we show that ORC1 - a component of ORC (origin of replication complex), which mediates pre-DNA replication licensing - contains a bromo adjacent homology (BAH) domain that specifically recognizes histone H4 dimethylated at lysine 20 (H4K20me2). Recognition of H4K20me2 is a property common to BAH domains present within diverse metazoan ORC1 proteins. Structural studies reveal that the specificity of the BAH domain for H4K20me2 is mediated by a dynamic aromatic dimethyl-lysine-binding cage and multiple intermolecular contacts involving the bound peptide. H4K20me2 is enriched at replication origins, and abrogating ORC1 recognition of H4K20me2 in cells impairs ORC1 occupancy at replication origins, ORC chromatin loading and cell-cycle progression. Mutation of the ORC1 BAH domain has been implicated in the aetiology of Meier-Gorlin syndrome (MGS), a form of primordial dwarfism, and ORC1 depletion in zebrafish results in an MGS-like phenotype. We find that wild-type human ORC1, but not ORC1-H4K20me2-binding mutants, rescues the growth retardation of orc1 morphants. Moreover, zebrafish depleted of H4K20me2 have diminished body size, mirroring the phenotype of orc1 morphants. Together, our results identify the BAH domain as a novel methyl-lysine-binding module, thereby establishing the first direct link between histone methylation and the metazoan DNA replication machinery, and defining a pivotal aetiological role for the canonical H4K20me2 mark, via ORC1, in primordial dwarfism.

  9. Transgenerational developmental effects and genomic instability after X-irradiation of preimplantation embryos: Studies on two mouse strains

    Energy Technology Data Exchange (ETDEWEB)

    Jacquet, P., E-mail: pjacquet@sckcen.be [Molecular and Cellular Biology, Institute for Environment, Health and Safety, SCK.CEN, Boeretang 200, B-2400 Mol (Belgium); Buset, J.; Neefs, M. [Molecular and Cellular Biology, Institute for Environment, Health and Safety, SCK.CEN, Boeretang 200, B-2400 Mol (Belgium); Vankerkom, J. [Division of Environmental Research, VITO, Boeretang 200, B-2400 Mol (Belgium); Benotmane, M.A.; Derradji, H. [Molecular and Cellular Biology, Institute for Environment, Health and Safety, SCK.CEN, Boeretang 200, B-2400 Mol (Belgium); Hildebrandt, G. [Department of Radiotherapy and Radiation Oncology, University of Leipzig, Stephanstrasse 9a, D-04103 Leipzig (Germany); Department of Radiotherapy, University of Rostock, Suedring 75, D-18059 Rostock (Germany); Baatout, S. [Molecular and Cellular Biology, Institute for Environment, Health and Safety, SCK.CEN, Boeretang 200, B-2400 Mol (Belgium)

    2010-05-01

    Recent results have shown that irradiation of a single cell, the zygote or 1-cell embryo of various mouse strains, could lead to congenital anomalies in the fetuses. In the Heiligenberger strain, a link between the radiation-induced congenital anomalies and the development of a genomic instability was also suggested. Moreover, further studies showed that in that strain, both congenital anomalies and genomic instability could be transmitted to the next generation. The aim of the experiments described in this paper was to investigate whether such non-targeted transgenerational effects could also be observed in two other radiosensitive mouse strains (CF1 and ICR), using lower radiation doses. Irradiation of the CF1 and ICR female zygotes with 0.2 or 0.4 Gy did not result in a decrease of their fertility after birth, when they had reached sexual maturity. Moreover, females of both strains that had been X-irradiated with 0.2 Gy exhibited higher rates of pregnancy, less resorptions and more living fetuses. Additionally, the mean weight of living fetuses in these groups had significantly increased. Exencephaly and dwarfism were observed in CF1 fetuses issued from control and X-irradiated females. In the control group of that strain, polydactyly and limb deformity were also found. The yields of abnormal fetuses did not differ significantly between the control and X-irradiated groups. Polydactyly, exencephaly and dwarfism were observed in fetuses issued from ICR control females. In addition to these anomalies, gastroschisis, curly tail and open eye were observed at low frequencies in ICR fetuses issued from X-irradiated females. Again, the frequencies of abnormal fetuses found in the different groups did not differ significantly. In both CF1 and ICR mouse strains, irradiation of female zygotes did not result in the development of a genomic instability in the next generation embryos. Overall, our results suggest that, at the moderate doses used, developmental defects

  10. Loss of imprinting at the Dlk1-Gtl2 locus caused by insertional mutagenesis in the Gtl2 5' region

    Directory of Open Access Journals (Sweden)

    Appelbe Oliver K

    2006-10-01

    Full Text Available Abstract Background The Dlk1 and Gtl2 genes define a region of mouse chromosome 12 that is subject to genomic imprinting, the parental allele-specific expression of a gene. Although imprinted genes play important roles in growth and development, the mechanisms by which imprinting is established and maintained are poorly understood. Differentially methylated regions (DMRs, which carry methylation on only one parental allele, are involved in imprinting control at many loci. The Dlk1-Gtl2 region contains three known DMRs, the Dlk1 DMR in the 3' region of Dlk1, the intergenic DMR 15 kb upstream of Gtl2, and the Gtl2 DMR at the Gtl2 promoter. Three mouse models are analyzed here that provide new information about the regulation of Dlk1-Gtl2 imprinting. Results A previously existing insertional mutation (Gtl2lacZ, and a targeted deletion in which the Gtl2 upstream region was replaced by a Neo cassette (Gtl2Δ5'Neo, display partial lethality and dwarfism upon paternal inheritance. Molecular characterization shows that both mutations cause loss of imprinting and changes in expression of the Dlk1, Gtl2 and Meg8/Rian genes. Dlk1 levels are decreased upon paternal inheritance of either mutation, suggesting Dlk1 may be causative for the lethality and dwarfism. Loss of imprinting on the paternal chromosome in both Gtl2lacZ and Gtl2Δ5'Neo mice is accompanied by the loss of paternal-specific Gtl2 DMR methylation, while maternal loss of imprinting suggests a previously unknown regulatory role for the maternal Gtl2 DMR. Unexpectedly, when the Neo gene is excised, Gtl2Δ5' animals are of normal size, imprinting is unchanged and the Gtl2 DMR is properly methylated. The exogenous DNA sequences integrated upstream of Gtl2 are therefore responsible for the growth and imprinting effects. Conclusion These data provide further evidence for the coregulation of the imprinted Dlk1 and Gtl2 genes, and support a role for Dlk1 as an important neonatal growth factor. The

  11. Osseous abnormalities and CT findings in stueve-wiedemann-syndrome (SWS); Ossaere Manifestationen und CT-Befunde bei der seltenen Skelettdysplasie Stueve-Wiedemann (SWS)

    Energy Technology Data Exchange (ETDEWEB)

    Langer, R. [UAE University, Dept. of Radiology, Al Ain (United Arab Emirates); Al-Gazali, L. [UAE University, Dept. of Paediatrics (United Arab Emirates); Haas, D. [FMHS - UAE Univ. and Tawam Hospital - Dept. of Radiology (United Arab Emirates); Raupp, P.; Varady, E. [Dept. of Paediatrics Al Ain (United Arab Emirates)

    2004-02-01

    Purpose: analysis of typical conventional radiological and CT findings in our group of patients with the rare skeletal dysplasia Stueve-Wiedemann-Syndrome (SWS) and comparison with published data. Materials and methods: in 16 newborns with clinically dysmorphic features, dwarfism, and bowed limbs, radiographs of the chest and skeleton were obtained for classification of the underlying skeletal dysplasia. For the first time, computed tomography was performed for further investigation of midface hypoplasia. The early diagnosis of SWS could be made by correlation of the radiological and clinical findings. For evaluation of progression, follow-up radiological examinations of the skeleton were performed in four children surviving infancy. Results: clinically, the newborns with SWS showed dwarfisms, midface hypoplasia, bowed extremities with contractures and had severe problems with respiration, feeding, and swallowing as well as episodes of hyperthermia. Skeletal radiographs revealed bowing of the long tubular bones, most pronounced at the lower extremities. Additional findings were internal triangular cortical diaphyseal thickening at the concave side of the bowing, wide metaphyses with abnormal trabecular pattern and radiolucencies. Four patients survived infancy. Clinically, they suffered from recurrent aspiration pneumonia and recurrent episodes of hyperthermia as well as form cutaneous and mucosal infections. The follow-up radiographs showed progressive bowing of the long tubular bones as well as progressive metaphyseal decalcification. Conclusions: skeletal abnormalities in SWS are so characteristic that an early post partum diagnosis can be made. However, a close cooperation between radiologists, clinicians, and geneticists is required for correlation of clinical and radiological findings. The few cases that survive infancy have progressing orthopaedic problems. (orig.) [German] Ziel: Die typischen radiologischen und CT-Befunde beim kongenitalen Stueve

  12. Impact of trace metal concentrations on coccolithophore growth and morphology: species-specific responses in past and present ocean

    Science.gov (United States)

    Faucher, Giulia; Hoffmann, Linn; Bach, Lennart Thomas; Bottini, Cinzia; Erba, Elisabetta; Riebesell, Ulf

    2017-04-01

    The Cretaceous witnessed intervals of profound perturbation named "Oceanic Anoxic Events (OAEs)" characterized by volcanic injection of large amounts of CO2, ocean anoxia, eutrophication, and introduction of biologically relevant metals. Some of these extreme events were characterized by size reduction and/or morphological changes of a number of nannofossil species. To detect the cause/s of such changes in the fossil record is challenging. Evidence of a correspondence between intervals of high trace metals concentrations and nannofossil dwarfism may be suggestive for a negative effect of these elements on nannoplankton biocalcification process. In order to verify the hypothesis that anomalously high quantities of essential and/or toxic metals were the cause of coccolith dwarfism, we explored the toxicities of a mixture of trace metals on four living coccolithophores species, namely Emiliania huxleyi, Gephyrocapsa oceanica, Pleurochrysis carterae and Coccolithus pelagicus. The trace metals tested were chosen based upon concentration peaks identified in the geological record and upon known trace metal interaction with living coccolithophores algae. Our results demonstrate a species-specific response to trace metal enrichment in living coccolithophores: E. huxleyi, G. oceanica and C. pelagicus showed a decrease in their growth rate with progressively and exponentially increased trace metal concentrations, while P. carterae is unresponsive to trace metal content. Furthermore, E. huxleyi, G. oceanica and C. pelagicus evidenced a decrease in the cell diameter. Smaller coccoliths were detected in E. huxleyi and C. pelagicus, while coccolith of G. oceanica showed a decrease in size only at the highest trace metal concentrations tested. P. carterae size was unresponsive for changing trace metal concentration. Our results on living coccolithophore algae, demonstrate that elevated trace metal concentrations not only affect growth but also coccolith size and/or weight and that

  13. De morseir syndrome presenting as ambiguous genitalia

    Directory of Open Access Journals (Sweden)

    Anubhav Thukral

    2012-01-01

    Full Text Available Background: A 10-year-old boy presented with genital ambiguity, poor linear growth, and delayed milestones. The aim and to highlight that although rare but congenital, hypogonadotropic hypogonadism may rarely present as ambiguity. Materials and Methods: The patient was found to have bilateral cryptorchidism with proximal penile hypospadias, microphallus with a proportionate dwarfism with mildly delayed bone age, and karyotype 46XY. Euthyroid with normal steroid axis, growth hormone insufficient as suggested by auxology, low IGF1, and poor response to clonidine stimulation. MRI brain shows hypoplastic corpus callosum, hypoplastic anterior pituitary, and ectopic posterior pituitary bright spot. Results: The patient underwent laparoscopic removal of right intrabdominal testis and orchidoplexy was performed on the left one. Testicular biopsy revealed no malignancy and growth hormone replacement was initiated. The patient awaits definitive repair of hypospadias. Conclusion: As a provisional diagnosis of combined growth hormone and gonadotropin deficiency, most probable diagnosis is septo-optic dysplasia or de moseir syndrome leading to genital ambiguity.

  14. FGFR signalling in women's cancers.

    Science.gov (United States)

    Fearon, Abbie E; Gould, Charlotte R; Grose, Richard P

    2013-12-01

    FGFs, in a complex with their receptors (FGFRs) and heparan sulfate (HS), are responsible for a range of cellular functions, from embryogenesis to metabolism. Both germ line and somatic FGFR mutations are known to play a role in a range of diseases, most notably craniosynestosis dysplasias, dwarfism and cancer. Because of the ability of FGFR signalling to induce cell proliferation, migration and survival, FGFRs are readily co-opted by cancer cells. Mutations in, and amplifications of, these receptors are found in a range of cancers with some of the most striking clinical findings relating to their contribution to pathogenesis and progression of female cancers. Here, we outline the molecular mechanisms of FGFR signalling and discuss the role of this pathway in women's cancers, focusing on breast, endometrial, ovarian and cervical carcinomas, and their associated preclinical and clinical data. We also address the rationale for therapeutic intervention and the need for FGFR-targeted therapy to selectively target cancer cells in view of the fundamental roles of FGF signalling in normal physiology.

  15. Multikinase activity of fibroblast growth factor receptor (FGFR) inhibitors SU5402, PD173074, AZD1480, AZD4547 and BGJ398 compromises the use of small chemicals targeting FGFR catalytic activity for therapy of short-stature syndromes.

    Science.gov (United States)

    Gudernova, Iva; Vesela, Iva; Balek, Lukas; Buchtova, Marcela; Dosedelova, Hana; Kunova, Michaela; Pivnicka, Jakub; Jelinkova, Iva; Roubalova, Lucie; Kozubik, Alois; Krejci, Pavel

    2016-01-01

    Activating mutations in the fibroblast growth factor receptor 3 (FGFR3) cause the most common genetic form of human dwarfism, achondroplasia (ACH). Small chemical inhibitors of FGFR tyrosine kinase activity are considered to be viable option for treating ACH, but little experimental evidence supports this claim. We evaluated five FGFR tyrosine kinase inhibitors (TKIs) (SU5402, PD173074, AZD1480, AZD4547 and BGJ398) for their activity against FGFR signaling in chondrocytes. All five TKIs strongly inhibited FGFR activation in cultured chondrocytes and limb rudiment cultures, completely relieving FGFR-mediated inhibition of chondrocyte proliferation and maturation. In contrast, TKI treatment of newborn mice did not improve skeletal growth and had lethal toxic effects on the liver, lungs and kidneys. In cell-free kinase assays as well as in vitro and in vivo cell assays, none of the tested TKIs demonstrated selectivity for FGFR3 over three other FGFR tyrosine kinases. In addition, the TKIs exhibited significant off-target activity when screened against a panel of 14 unrelated tyrosine kinases. This was most extensive in SU5402 and AZD1480, which inhibited DDR2, IGF1R, FLT3, TRKA, FLT4, ABL and JAK3 with efficiencies similar to or greater than those for FGFR. Low target specificity and toxicity of FGFR TKIs thus compromise their use for treatment of ACH. Conceptually, different avenues of therapeutic FGFR3 targeting should be investigated.

  16. Altered expression of cytosolic/nuclear HSC70-1 molecular chaperone affects development and abiotic stress tolerance in Arabidopsis thaliana.

    Science.gov (United States)

    Cazalé, Anne-Claire; Clément, Mathilde; Chiarenza, Serge; Roncato, Marie-Anne; Pochon, Nathalie; Creff, Audrey; Marin, Elena; Leonhardt, Nathalie; Noël, Laurent D

    2009-01-01

    Molecular chaperones of the heat shock cognate 70 kDa (HSC70) family are highly conserved in all living organisms and assist nascent protein folding in normal physiological conditions as well as in biotic and abiotic stress conditions. In the absence of specific inhibitors or viable knockout mutants, cytosolic/nuclear HSC70-1 overexpression (OE) and mutants in the HSC70 co-chaperone SGT1 (suppressor of G(2)/M allele of skp1) were used as genetic tools to identify HSC70/SGT1 functions in Arabidopsis development and abiotic stress responses. HSC70-1 OE caused a reduction in root and shoot meristem activities, thus explaining the dwarfism of those plants. In addition, HSC70-1 OE did not impair auxin-dependent phenotypes, suggesting that SGT1 functions previously identified in auxin signalling are HSC70 independent. While responses to abiotic stimuli such as UV-C exposure, phosphate starvation, or seedling de-etiolation were not perturbed by HSC70-1 OE, it specifically conferred gamma-ray hypersensitivity and tolerance to salt, cadmium (Cd), and arsenic (As). Cd and As perception was not perturbed, but plants overexpressing HSC70-1 accumulated less Cd, thus providing a possible molecular explanation for their tolerance phenotype. In summary, genetic evidence is provided for HSC70-1 involvement in a limited set of physiological processes, illustrating the essential and yet specific functions of this chaperone in development and abiotic stress responses in Arabidopsis.

  17. Partial isodisomy for maternal chromosome 7 and short stature in an individual with a mutation at the COL1A2 locus.

    Science.gov (United States)

    Spotila, L D; Sereda, L; Prockop, D J

    1992-12-01

    Uniparental disomy for chromosome 7 has been described previously in two individuals with cystic fibrosis. Here, we describe a third case that was discovered because the proband was homozygous for a mutation in the COL1A2 gene for type I procollagen, although his mother was heterozygous and his father did not have the mutation. Phenotypically, the proband was similar to the two previously reported cases with uniparental disomy for chromosome 7, in that he was short in stature and growth retarded. Paternity was assessed with five polymorphic markers. Chromosome 7 inheritance in the proband was analyzed using 12 polymorphic markers distributed along the entire chromosome. Similar analysis of the proband's two brothers established the phase of the alleles at the various loci, assuming minimal recombination. The proband inherited only maternal alleles at five loci and was homozygous at all loci examined, except one. He was heterozygous for an RFLP at the IGBP-1 locus at 7p13-p12. The results suggest that the isodisomy was not complete because of a recombination event involving the proximal short arms of two maternal chromosomes. In addition, the phenotype of proportional dwarfism in the proband suggests imprinting of one or more growth-related genes on chromosome 7.

  18. Partial isodisomy for maternal chromosome 7 and short stature in an individual with a mutation at the COL1A2 locus

    Energy Technology Data Exchange (ETDEWEB)

    Spotila, L.D.; Sereda, L.; Prockop, D.J. (Jefferson Medical College, Philadelphia, PA (United States))

    1992-12-01

    Uniparental disomy for chromosome 7 has been described previously in two individuals with cystic fibrosis. Here, the authors describe a third case that was discovered because the proband was homozygous for a mutation in the COL1A2 gene for type I procollagen, although his mother was heterozygous and his father did not have the mutation. Phenotypically, the proband was similar to the two previously reported cases with uniparental disomy for chromosome 7, in that he was short in stature and growth retarded. Paternity was assessed with five polymorphic markers. Chromosome 7 inheritance in the proband was analyzed using 12 polymorphic markers distributed along the entire chromosome. Similar analysis of the proband's two brothers established the phase of the alleles at the various loci, assuming minimal recombination. The proband inherited only maternal alleles at five loci and was homozygous at all loci examined, except one. He was heterozygous for an RFLP at the IGBP-1 locus at 7p13-p12. The results suggest that the isodisomy was not complete because of a recombination event involving the proximal short arms of two maternal chromosomes. In addition, the phenotype of proportional dwarfism in the proband suggests imprinting of one or more growth-related genes on chromosome 7. 42 refs., 5 figs., 3 tabs.

  19. Isolation and Genomic Characterization of a Duck-Origin GPV-Related Parvovirus from Cherry Valley Ducklings in China.

    Science.gov (United States)

    Chen, Hao; Dou, Yanguo; Tang, Yi; Zhang, Zhenjie; Zheng, Xiaoqiang; Niu, Xiaoyu; Yang, Jing; Yu, Xianglong; Diao, Youxiang

    2015-01-01

    A newly emerged duck parvovirus, which causes beak atrophy and dwarfism syndrome (BADS) in Cherry Valley ducks, has appeared in Northern China since March 2015. To explore the genetic diversity among waterfowl parvovirus isolates, the complete genome of an identified isolate designated SDLC01 was sequenced and analyzed in the present study. Genomic sequence analysis showed that SDLC01 shared 90.8%-94.6% of nucleotide identity with goose parvovirus (GPV) isolates and 78.6%-81.6% of nucleotide identity with classical Muscovy duck parvovirus (MDPV) isolates. Phylogenetic analysis of 443 nucleotides (nt) of the fragment A showed that SDLC01 was highly similar to a mule duck isolate (strain D146/02) and close to European GPV isolates but separate from Asian GPV isolates. Analysis of the left inverted terminal repeat regions revealed that SDLC01 had two major segments deleted between positions 160-176 and 306-322 nt compared with field GPV and MDPV isolates. Phylogenetic analysis of Rep and VP1 encoded by two major open reading frames of parvoviruses revealed that SDLC01 was distinct from all GPV and MDPV isolates. The viral pathogenicity and genome characterization of SDLC01 suggest that the novel GPV (N-GPV) is the causative agent of BADS and belongs to a distinct GPV-related subgroup. Furthermore, N-GPV sequences were detected in diseased ducks by polymerase chain reaction and viral proliferation was demonstrated in duck embryos and duck embryo fibroblast cells.

  20. Development of a TaqMan-based real-time PCR assay for the detection of Novel GPV.

    Science.gov (United States)

    Niu, Xiaoyu; Chen, Hao; Yang, Jing; Yu, Xianglong; Ti, Jinfeng; Wang, Aihua; Diao, Youxiang

    2016-11-01

    The newly emerged disease, duck beak atrophy and dwarfism syndrome (BADS), is caused by novel goose parovirus (N-GPV). Although N-GPV infection has severe consequences, few methods for detecting this virus have been developed. Therefore, the availability of rapid and reliable molecular diagnostic methods would aid future studies of this novel virus. Clinical specimens from 138 suspected cases of N-GPV infection and 120 cloacal swabs from breeding ducks were used in this study. The targeted sequence of N-GPV cloned into the pMD18-T vector was used to generate the N-GPV DNA standard curve. The specificity of the assay was validated using duck plague virus, GPV, duck hepatitis virus, avian influenza virus, duck reovirus, tembusu virus, and fowl adenovirus. The lowest limit of detection was 8.8×10(1)copies/μL with a good linear standard curve (Y=-3.3682X+37.220, R(2)=0.9953) over a wide range of input DNA, of which the concentration was between 8.8×10(1) to 8.8×10(8)copies/μL. The results show that the real-time PCR assay is a highly sensitive, specific, reproducible, and versatile method for quantitatively detecting N-GPV DNA, and thus can be used to detect this virus, thereby facilitating epidemiological investigations of animals with BADS. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Fetal deficiency of lin28 programs life-long aberrations in growth and glucose metabolism.

    Science.gov (United States)

    Shinoda, Gen; Shyh-Chang, Ng; Soysa, T Yvanka de; Zhu, Hao; Seligson, Marc T; Shah, Samar P; Abo-Sido, Nora; Yabuuchi, Akiko; Hagan, John P; Gregory, Richard I; Asara, John M; Cantley, Lewis C; Moss, Eric G; Daley, George Q

    2013-08-01

    LIN28A/B are RNA binding proteins implicated by genetic association studies in human growth and glucose metabolism. Mice with ectopic over-expression of Lin28a have shown related phenotypes. Here, we describe the first comprehensive analysis of the physiologic consequences of Lin28a and Lin28b deficiency in knockout (KO) mice. Lin28a/b-deficiency led to dwarfism starting at different ages, and compound gene deletions showed a cumulative dosage effect on organismal growth. Conditional gene deletion at specific developmental stages revealed that fetal but neither neonatal nor adult deficiency resulted in growth defects and aberrations in glucose metabolism. Tissue-specific KO mice implicated skeletal muscle-deficiency in the abnormal programming of adult growth and metabolism. The effects of Lin28b KO could be rescued by Tsc1 haplo-insufficiency in skeletal muscles. Our data implicate fetal expression of Lin28a/b in the regulation of life-long effects on metabolism and growth, and demonstrate that fetal Lin28b acts at least in part via mTORC1 signaling.

  2. Value of systematic post mortem radiographic examinations of fetuses - 400 cases

    Energy Technology Data Exchange (ETDEWEB)

    Kalifa, G.; Sellier, N.; Barbet, J.P.; Labbe, F.; Houette, A.

    1989-01-01

    A retrospective study of 400 cases of fetal deaths has been carried out to assess the value of systematic post mortem radiological examination. Apart from general diagnosis purpose, special attention was given to the assessment of bone age and mineralization. The results were correlated with the clinical, U.S., chromosomal and pathological data. Computerized analysis of our information show the following results: (1) The radiological examination was valuable for the final diagnosis in 13.5% of cases. (2) It brings additional information in 34.5% of cases. (3) It had no diagnostic value in 52%. Furthermore several points deserve attention such as apparition of teeth (21 weeks), calcaneum (24 weeks). Major osteoporosis was always associated with a constitutional bone disease or an infectious process. An excessive length of the upper limbs (12) was seen in 11 cases of anencephaly. We suggest that a radiological examination should not be routinely performed, when the diagnosis is otherwise obvious, but should be considered in the presence of dwarfism, or other limb abnormalities and when the gestational age is uncertain. The films provide essential information especially for further genetic counselling.

  3. Structural Variations in Articular Cartilage Matrix Are Associated with Early-Onset Osteoarthritis in the Spondyloepiphyseal Dysplasia Congenita (Sedc Mouse

    Directory of Open Access Journals (Sweden)

    Robert E. Seegmiller

    2013-08-01

    Full Text Available Heterozgyous spondyloepiphyseal dysplasia congenita (sedc/+ mice expressing a missense mutation in col2a1 exhibit a normal skeletal morphology but early-onset osteoarthritis (OA. We have recently examined knee articular cartilage obtained from homozygous (sedc/sedc mice, which express a Stickler-like phenotype including dwarfism. We examined sedc/sedc mice at various levels to better understand the mechanistic process resulting in OA. Mutant sedc/sedc, and control (+/+ cartilages were compared at two, six and nine months of age. Tissues were fixed, decalcified, processed to paraffin sections, and stained with hematoxylin/eosin and safranin O/fast green. Samples were analyzed under the light microscope and the modified Mankin and OARSI scoring system was used to quantify the OA-like changes. Knees were stained with 1C10 antibody to detect the presence and distribution of type II collagen. Electron microscopy was used to study chondrocyte morphology and collagen fibril diameter. Compared with controls, mutant articular cartilage displayed decreased fibril diameter concomitant with increases in size of the pericellular space, Mankin and OARSI scores, cartilage thickness, chondrocyte clustering, proteoglycan staining and horizontal fissuring. In conclusion, homozygous sedc mice are subject to early-onset knee OA. We conclude that collagen in the mutant’s articular cartilage (both heterozygote and homozygote fails to provide the normal meshwork required for matrix integrity and overall cartilage stability.

  4. Plastidial NAD-dependent malate dehydrogenase is critical for embryo development and heterotrophic metabolism in Arabidopsis.

    Science.gov (United States)

    Beeler, Seraina; Liu, Hung-Chi; Stadler, Martha; Schreier, Tina; Eicke, Simona; Lue, Wei-Ling; Truernit, Elisabeth; Zeeman, Samuel C; Chen, Jychian; Kötting, Oliver

    2014-03-01

    In illuminated chloroplasts, one mechanism involved in reduction-oxidation (redox) homeostasis is the malate-oxaloacetate (OAA) shuttle. Excess electrons from photosynthetic electron transport in the form of nicotinamide adenine dinucleotide phosphate, reduced are used by NADP-dependent malate dehydrogenase (MDH) to reduce OAA to malate, thus regenerating the electron acceptor NADP. NADP-MDH is a strictly redox-regulated, light-activated enzyme that is inactive in the dark. In the dark or in nonphotosynthetic tissues, the malate-OAA shuttle was proposed to be mediated by the constitutively active plastidial NAD-specific MDH isoform (pdNAD-MDH), but evidence is scarce. Here, we reveal the critical role of pdNAD-MDH in Arabidopsis (Arabidopsis thaliana) plants. A pdnad-mdh null mutation is embryo lethal. Plants with reduced pdNAD-MDH levels by means of artificial microRNA (miR-mdh-1) are viable, but dark metabolism is altered as reflected by increased nighttime malate, starch, and glutathione levels and a reduced respiration rate. In addition, miR-mdh-1 plants exhibit strong pleiotropic effects, including dwarfism, reductions in chlorophyll levels, photosynthetic rate, and daytime carbohydrate levels, and disordered chloroplast ultrastructure, particularly in developing leaves, compared with the wild type. pdNAD-MDH deficiency in miR-mdh-1 can be functionally complemented by expression of a microRNA-insensitive pdNAD-MDH but not NADP-MDH, confirming distinct roles for NAD- and NADP-linked redox homeostasis.

  5. Short stature with umbilical hernia - Not always due to cretinism: A report of two cases

    Directory of Open Access Journals (Sweden)

    Sharvil S Gadve

    2012-01-01

    Full Text Available A 7-year-old boy presented with umbilical hernia and short stature. Growth retardation, recurrent upper respiratory tract infections and delayed developmental milestones were present from infancy. Umbilical hernia was diagnosed at the age of 5 years. On examination, he had short-trunk dwarfism, large head circumference, coarse facial features, joint stiffness, hepatosplenomegaly, and mild mental retardation. He had normal biochemical parameters, thyroid function tests and arterial blood gas analysis. Radiological evaluation showed that the child had Hunter syndrome with findings of J-shaped sellaturcica, proximal bulleting of metacarpals, spatulated ribs and anterior beaking of lumbar vertebrae. The second case was a 6-year-old girl with umbilical hernia, short stature, normal biochemistry and radiological findings of mucopolysaccharidosis. However, she also had corneal opacity; confirmed by slit-lamp examination, which led to the diagnosis of Hurler-Scheie syndrome. Enzymatic studies could not be done in both the cases, as they are not available at most centers.

  6. Pathogenesis of Morquio A syndrome: an autopsied case reveals systemic storage disorder.

    Science.gov (United States)

    Yasuda, Eriko; Fushimi, Kazunari; Suzuki, Yasuyuki; Shimizu, Katsuji; Takami, Tsuyoshi; Zustin, Jozef; Patel, Pravin; Ruhnke, Kristen; Shimada, Tsutomu; Boyce, Bobbie; Kokas, Terry; Barone, Carol; Theroux, Mary; Mackenzie, William; Nagel, Barbara; Ryerse, Jan S; Orii, Kenji E; Iida, Hiroki; Orii, Tadao; Tomatsu, Shunji

    2013-07-01

    Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage disorder caused by deficiency of N-acetylgalactosamine-6-sulfate sulfatase, which results in systemic accumulation of glycosaminoglycans (GAGs), keratan sulfate and chondroitin-6-sulfate. Accumulation of these GAGs causes characteristic features as disproportionate dwarfism associated with skeletal deformities, genu valgum, pigeon chest, joint laxity, and kyphoscoliosis. However, the pathological mechanism of systemic skeletal dysplasia and involvement of other tissues remain unanswered in the paucity of availability of an autopsied case and successive systemic analyses of multiple tissues. We report here a 20-year-old male autopsied case with MPS IVA, who developed characteristic skeletal features by the age of 1.5 years and died of acute respiratory distress syndrome five days later after occipito-C1-C2 cervical fusion. We pathohistologically analyzed postmortem tissues including trachea, lung, thyroid, humerus, aorta, heart, liver, spleen, kidney, testes, bone marrow, and lumbar vertebrae. The postmortem tissues relevant with clinical findings demonstrated 1) systemic storage materials in multiple tissues beyond cartilage, 2) severely vacuolated and ballooned chondrocytes in trachea, humerus, vertebrae, and thyroid cartilage with disorganized extracellular matrix and poor ossification, 3) appearance of foam cells and macrophages in lung, aorta, heart valves, heart muscle, trachea, visceral organs, and bone marrow, and 4) storage of chondrotin-6-sulfate in aorta. This is the first autopsied case with MPS IVA whose multiple tissues have been analyzed pathohistologically and these pathological findings should provide a new insight into pathogenesis of MPS IVA.

  7. Chromosomal instability associated with a novel BLM frameshift mutation (c.1980-1982delAA) in two unrelated Tunisian families with Bloom syndrome.

    Science.gov (United States)

    Ben Salah, G; Salem, I Hadj; Masmoudi, A; Ben Rhouma, B; Turki, H; Fakhfakh, F; Ayadi, H; Kamoun, H

    2014-10-01

    The Bloom syndrome (BS) is an autosomal recessive disorder associated with dwarfism, immunodeficiency, reduced fertility and cancer risk. BS cells show genomic instability, particularly an hyper exchange between the sister chromatids due to a defective processing of the DNA replication intermediates. It is caused by mutations in the BLM gene which encodes a member of the RecQ family of DExH box DNA helicases. In this study, we reported cytogenetic, BLM linkage and mutational analyses for two affected Tunisian families. The Cytogenetic parameters were performed by chromosomal aberration (CA) and sister chromatid exchange (SCE) assays and results showed a significant increase in mean frequency of CA and SCE in BS cells. BLM linkage performed by microsatellite genotyping revealed homozygous haplotypes for the BS patients, evidence of linkage to BLM gene. Mutational analysis by direct DNA sequencing revealed a novel frameshift mutation (c.1980-1982delAA) in exon 8 of BLM gene, resulting in a truncated protein (p.Lys662fsX5). The truncated protein could explain genomic instability and its related symptoms in the BS patients. The screening of this mutation is useful for BS diagnosis confirmation in Tunisian families.

  8. Case Report: Atypical Cornelia de Lange Syndrome [version 2; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Vito Leanza

    2015-05-01

    Full Text Available Cornelia de Lange Syndrome (CdLS (also called Bushy Syndrome or Amsterdam dwarfism, is a genetic disorder that can lead to several alterations. This disease affects both physical and neuropsychiatric development. The various abnormalities include facial dysmorphia (arched eyebrows, synophrys, depressed nasal bridge, long philtrum, down-turned angles of the mouth, upper-extremity malformations, hirsutism, cardiac defects, and gastrointestinal alterations. The prevalence of this syndrome is approximately one per 15,000. Ultrasound is not the perfect means to diagnose CdLS, however, many abnormalities can be detected prenatally by scrupulous image observation. We report an atypical CdLS case characterized by increased nuchal translucency in the first trimester, normal karyotype, saddle nose, micrognathia with receding jaw, low set ears, facies senilis, arthrogryposis of the hands, absence of the Aranzio ductus venous, dilatation of gallbladder and bowel, a unique umbilical artery, increased volume of amniotic fluid, and intrauterine growth retardation ending with the interruption of pregnancy.

  9. Altered architecture and enhanced drought tolerance in rice via the down-regulation of indole-3-acetic acid by TLD1/OsGH3.13 activation.

    Science.gov (United States)

    Zhang, Sheng-Wei; Li, Chen-Hui; Cao, Jia; Zhang, Yong-Cun; Zhang, Su-Qiao; Xia, Yu-Feng; Sun, Da-Ye; Sun, Ying

    2009-12-01

    Plant architecture is determined by genetic and developmental programs as well as by environmental factors. Sessile plants have evolved a subtle adaptive mechanism that allows them to alter their growth and development during periods of stress. Phytohormones play a central role in this process; however, the molecules responsible for integrating growth- and stress-related signals are unknown. Here, we report a gain-of-function rice (Oryza sativa) mutant, tld1-D, characterized by (and named for) an increased number of tillers, enlarged leaf angles, and dwarfism. TLD1 is a rice GH3.13 gene that encodes indole-3-acetic acid (IAA)-amido synthetase, which is suppressed in aboveground tissues under normal conditions but which is dramatically induced by drought stress. The activation of TLD1 reduced the IAA maxima at the lamina joint, shoot base, and nodes, resulting in subsequent alterations in plant architecture and tissue patterning but enhancing drought tolerance. Accordingly, the decreased level of free IAA in tld1-D due to the conjugation of IAA with amino acids greatly facilitated the accumulation of late-embryogenesis abundant mRNA compared with the wild type. The direct regulation of such drought-inducible genes by changes in the concentration of IAA provides a model for changes in plant architecture via the process of drought adaptation, which occurs frequently in nature.

  10. Small-bodied humans from Palau, Micronesia.

    Directory of Open Access Journals (Sweden)

    Lee R Berger

    Full Text Available UNLABELLED: Newly discovered fossil assemblages of small bodied Homo sapiens from Palau, Micronesia possess characters thought to be taxonomically primitive for the genus Homo. BACKGROUND: Recent surface collection and test excavation in limestone caves in the rock islands of Palau, Micronesia, has produced a sizeable sample of human skeletal remains dating roughly between 940-2890 cal ybp. PRINCIPLE FINDINGS: Preliminary analysis indicates that this material is important for two reasons. First, individuals from the older time horizons are small in body size even relative to "pygmoid" populations from Southeast Asia and Indonesia, and thus may represent a marked case of human insular dwarfism. Second, while possessing a number of derived features that align them with Homo sapiens, the human remains from Palau also exhibit several skeletal traits that are considered to be primitive for the genus Homo. SIGNIFICANCE: These features may be previously unrecognized developmental correlates of small body size and, if so, they may have important implications for interpreting the taxonomic affinities of fossil specimens of Homo.

  11. A strategy to provide long-term control of weedy rice while mitigating herbicide resistance transgene flow, and its potential use for other crops with related weeds.

    Science.gov (United States)

    Gressel, Jonathan; Valverde, Bernal E

    2009-07-01

    Transgenic herbicide-resistant rice is needed to control weeds that have evolved herbicide resistance, as well as for the weedy (feral, red) rice problem, which has been exacerbated by shifting to direct seeding throughout the world-firstly in Europe and the Americas, and now in Asia, as well as in parts of Africa. Transplanting had been the major method of weedy rice control. Experience with imidazolinone-resistant rice shows that gene flow to weedy rice is rapid, negating the utility of the technology. Transgenic technologies are available that can contain herbicide resistance within the crop (cleistogamy, male sterility, targeting to chloroplast genome, etc.), but such technologies are leaky. Mitigation technologies tandemly couple (genetically link) the gene of choice (herbicide resistance) with mitigation genes that are neutral or good for the crop, but render hybrids with weedy rice and their offspring unfit to compete. Mitigation genes confer traits such as non-shattering, dwarfism, no secondary dormancy and herbicide sensitivity. It is proposed to use glyphosate and glufosinate resistances separately as genes of choice, and glufosinate, glyphosate and bentazone susceptibilities as mitigating genes, with a six-season rotation where each stage kills transgenic crop volunteers and transgenic crop x weed hybrids from the previous season.

  12. Hypochondroplasia, Acanthosis Nigricans, and Insulin Resistance in a Child with FGFR3 Mutation: Is It Just an Association?

    Directory of Open Access Journals (Sweden)

    Manal Mustafa

    2014-01-01

    Full Text Available FGFR3 mutations cause wide spectrum of disorders ranging from skeletal dysplasias (hypochondroplasia, achondroplasia, and thanatophoric dysplasia, benign skin tumors (epidermal nevi, seborrhaeic keratosis, and acanthosis nigricans, and epithelial malignancies (multiple myeloma and prostate and bladder carcinoma. Hypochondroplasia is the most common type of short-limb dwarfism in children resulting from fibroblast growth factor receptor 3 (FGFR3 mutation. Acanthosis nigricans might be seen in severe skeletal dysplasia, including thanatophoric dysplasia and SADDAN syndrome, without a biochemical evidence of hyperinsulinemia. Insulin insensitivity and acanthosis nigricans are uncommonly seen in hypochondroplasia patients with FGFR3 mutations which may represent a new association. We aim to describe the association of hypochondroplasia, acanthosis nigricans, and insulin resistance in a child harboring FGFR3 mutation. To our knowledge, this is the first case report associating the p.N540 with acanthosis nigricans and the second to describe hyperinsulinemia in hypochondroplasia. This finding demonstrates the possible coexistence of insulin insensitivity and acanthosis nigricans in hypochondroplasia patients.

  13. A simple and rapid quantitative method of detection of the common achondroplasia mutation: Analysis in mismatch repair deficient cells

    Directory of Open Access Journals (Sweden)

    Grewal Raji

    2004-01-01

    Full Text Available Achondroplasia is the most common form of dwarfism and has an incidence of approximately 1/7,500. In more than 97% of cases, it is caused by a recurrent point mutation, a G to A substitution at nucleotide position 1138 (G1138A of the fibroblast growth factor receptor 3 gene. Although this is an autosomal dominant condition, more than 90% of all mutations occur sporadically making this one of the most mutagenic sites in the human genome. The reasons for the high spontaneous G1138A mutation rate are not known. This investigation was performed by developing a simple and rapid semi-quantitative allele specific PCR based assay capable of reliably detecting more than 25 mutant G1138A copies in a pool of 300,000 wild type molecules. Using this assay, the G1138A mutation frequency was measured in cell lines deficient in mismatch repair (LoVo, SW48 and comparing it with controls. No differences were found in the frequency of this point mutation between the mismatch repair deficient and wild type cell lines.

  14. Arabidopsis VASCULAR-RELATED UNKNOWN PROTEIN1 regulates xylem development and growth by a conserved mechanism that modulates hormone signaling.

    Science.gov (United States)

    Grienenberger, Etienne; Douglas, Carl J

    2014-04-01

    Despite a strict conservation of the vascular tissues in vascular plants (tracheophytes), our understanding of the genetic basis underlying the differentiation of secondary cell wall-containing cells in the xylem of tracheophytes is still far from complete. Using coexpression analysis and phylogenetic conservation across sequenced tracheophyte genomes, we identified a number of Arabidopsis (Arabidopsis thaliana) genes of unknown function whose expression is correlated with secondary cell wall deposition. Among these, the Arabidopsis VASCULAR-RELATED UNKNOWN PROTEIN1 (VUP1) gene encodes a predicted protein of 24 kD with no annotated functional domains but containing domains that are highly conserved in tracheophytes. Here, we show that the VUP1 expression pattern, determined by promoter-β-glucuronidase reporter gene expression, is associated with vascular tissues, while vup1 loss-of-function mutants exhibit collapsed morphology of xylem vessel cells. Constitutive overexpression of VUP1 caused dramatic and pleiotropic developmental defects, including severe dwarfism, dark green leaves, reduced apical dominance, and altered photomorphogenesis, resembling brassinosteroid-deficient mutants. Constitutive overexpression of VUP homologs from multiple tracheophyte species induced similar defects. Whole-genome transcriptome analysis revealed that overexpression of VUP1 represses the expression of many brassinosteroid- and auxin-responsive genes. Additionally, deletion constructs and site-directed mutagenesis were used to identify critical domains and amino acids required for VUP1 function. Altogether, our data suggest a conserved role for VUP1 in regulating secondary wall formation during vascular development by tissue- or cell-specific modulation of hormone signaling pathways.

  15. Methylation of Gibberellins by Arabidopsis GAMT1 and GAMT2

    Energy Technology Data Exchange (ETDEWEB)

    Varbanova,M.; Yamaguchi, S.; Yang, Y.; McKelvey, K.; Hanada, A.; Borochov, R.; Yu, F.; Jikumaru, Y.; Ross, J.; et al

    2007-01-01

    Arabidopsis thaliana GAMT1 and GAMT2 encode enzymes that catalyze formation of the methyl esters of gibberellins (GAs). Ectopic expression of GAMT1 or GAMT2 in Arabidopsis, tobacco (Nicotiana tabacum), and petunia (Petunia hybrida) resulted in plants with GA deficiency and typical GA deficiency phenotypes, such as dwarfism and reduced fertility. GAMT1 and GAMT2 are both expressed mainly in whole siliques (including seeds), with peak transcript levels from the middle until the end of silique development. Within whole siliques, GAMT2 was previously shown to be expressed mostly in developing seeds, and we show here that GAMT1 expression is also localized mostly to seed, suggesting a role in seed development. Siliques of null single GAMT1 and GAMT2 mutants accumulated high levels of various GAs, with particularly high levels of GA1 in the double mutant. Methylated GAs were not detected in wild-type siliques, suggesting that methylation of GAs by GAMT1 and GAMT2 serves to deactivate GAs and initiate their degradation as the seeds mature. Seeds of homozygous GAMT1 and GAMT2 null mutants showed reduced inhibition of germination, compared with the wild type, when placed on plates containing the GA biosynthesis inhibitor ancymidol, with the double mutant showing the least inhibition. These results suggest that the mature mutant seeds contained higher levels of active GAs than wild-type seeds.

  16. Strigolactones stimulate internode elongation independently of gibberellins.

    Science.gov (United States)

    de Saint Germain, Alexandre; Ligerot, Yasmine; Dun, Elizabeth A; Pillot, Jean-Paul; Ross, John J; Beveridge, Christine A; Rameau, Catherine

    2013-10-01

    Strigolactone (SL) mutants in diverse species show reduced stature in addition to their extensive branching. Here, we show that this dwarfism in pea (Pisum sativum) is not attributable to the strong branching of the mutants. The continuous supply of the synthetic SL GR24 via the root system using hydroponics can restore internode length of the SL-deficient rms1 mutant but not of the SL-response rms4 mutant, indicating that SLs stimulate internode elongation via RMS4. Cytological analysis of internode epidermal cells indicates that SLs control cell number but not cell length, suggesting that SL may affect stem elongation by stimulating cell division. Consequently, SLs can repress (in axillary buds) or promote (in the stem) cell division in a tissue-dependent manner. Because gibberellins (GAs) increase internode length by affecting both cell division and cell length, we tested if SLs stimulate internode elongation by affecting GA metabolism or signaling. Genetic analyses using SL-deficient and GA-deficient or DELLA-deficient double mutants, together with molecular and physiological approaches, suggest that SLs act independently from GAs to stimulate internode elongation.

  17. Impact of Crab Bioturbation on Nitrogen-Fixation Rates in Red Sea Mangrove Sediment

    KAUST Repository

    Qashqari, Maryam S.

    2017-05-01

    Mangrove plants are a productive ecosystem that provide several benefits for marine organisms and industry. They are considered to be a food source and habitat for many organisms. However, mangrove growth is limited by nutrient availability. According to some recent studies, the dwarfism of the mangrove plants is due to the limitation of nitrogen in the environment. Biological nitrogen fixation is the process by which atmospheric nitrogen is fixed into ammonium. Then, this fixed nitrogen can be uptaken by plants. Hence, biological nitrogen fixation increases the input of nitrogen in the mangrove ecosystem. In this project, we focus on measuring the rates of nitrogen fixation on Red Sea mangrove (Avicennia marina) located at Thuwal, Saudi Arabia. The nitrogen fixation rates are calculated by the acetylene reduction assay. The experimental setup will allow us to analyze the effect of crab bioturbation on nitrogen fixing rates. This study will help to better understand the nitrogen dynamics in mangrove ecosystems in Saudi Arabia. Furthermore, this study points out the importance of the sediment microbial community in mangrove trees development. Finally, the role of nitrogen fixing bacteria should be taken in account for future restoration activities.

  18. Hyperphagic short stature: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Varsha S Jagtap

    2012-01-01

    Full Text Available A 5½-year-old adopted girl was referred to us in view of short stature. After ruling out systemic illness, she was evaluated for growth hormone deficiency (GHD by stimulation tests. The peak value was 3.47 ng/ml. She was then started on growth hormone (GH. At the end of 6 months of GH therapy, her height velocity was only 3 cm/year. There was a lack of attachment between the mother and the child. She had history of hyperphagia, stealing, and hoarding food. Psychiatry consultation confirmed that the child had appetite disorder, and hence was diagnosed as hyperphagic short stature (HSS. The girl and her parents are undergoing psychiatric therapy for the same. Psychosocial dwarfism seems to originate from serious disturbances in the mother-child relationship. These children mimic patients with GHD, but have poor response to GH therapy. This case underscores the importance of social environment in the growth of the individual.

  19. PHOSPHATIDYLSERINE SYNTHASE1 is Required for Inflorescence Meristem and Organ Development in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Chengwu Liu; Hengfu Yin; Peng Gao; Xiaohe Hu; Jun Yang; Zhongchi Liu; Xiangdong Fu

    2013-01-01

    Phosphatidylserine (PS),a quantitatively minor membrane phospholipid,is involved in many biological processes besides its role in membrane structure.One PS synthesis gene,PHOSPHATIDYLSERINE SYNTHASE1 (PSS1),has been discovered to be required for microspore development in Arabidopsis thaliana L.but how PSS1 affects postembryonic development is still largely unknown.Here,we show that PSS1 is also required for inflorescence meristem and organ development in Arabidopsis.Disruption of PSS1 causes severe dwarfism,smaller lateral organs and reduced size of inflorescence meristem.Morphological and molecular studies suggest that both cell division and cell elongation are affected in the pss1-1 mutant.RNA in situ hybridization and promoter GUS analysis show that expression of both WUSCHEL (WUS) and CLAVATA3 (CLV3) depend on PSS1.Moreover,the defect in meristem maintenance is recovered and the expression of WUS and CLV3 are restored in the pss1-1 clv1-1 double mutant.Both SHOOTSTEMLESS (STM) and BREVIPEDICELLUS (BP) are upregulated,and auxin distribution is disrupted in rosette leaves of pss1-1.However,expression of BP,which is also a regulator of internode development,is lost in the pss1-1 inflorescence stem.Our data suggest that PSS1 plays essential roles in inflorescence meristem maintenance through the WUS-CLV pathway,and in leaf and internode development by differentially regulating the class Ⅰ KNOX genes.

  20. The maximum rate of mammal evolution

    Science.gov (United States)

    Evans, Alistair R.; Jones, David; Boyer, Alison G.; Brown, James H.; Costa, Daniel P.; Ernest, S. K. Morgan; Fitzgerald, Erich M. G.; Fortelius, Mikael; Gittleman, John L.; Hamilton, Marcus J.; Harding, Larisa E.; Lintulaakso, Kari; Lyons, S. Kathleen; Okie, Jordan G.; Saarinen, Juha J.; Sibly, Richard M.; Smith, Felisa A.; Stephens, Patrick R.; Theodor, Jessica M.; Uhen, Mark D.

    2012-03-01

    How fast can a mammal evolve from the size of a mouse to the size of an elephant? Achieving such a large transformation calls for major biological reorganization. Thus, the speed at which this occurs has important implications for extensive faunal changes, including adaptive radiations and recovery from mass extinctions. To quantify the pace of large-scale evolution we developed a metric, clade maximum rate, which represents the maximum evolutionary rate of a trait within a clade. We applied this metric to body mass evolution in mammals over the last 70 million years, during which multiple large evolutionary transitions occurred in oceans and on continents and islands. Our computations suggest that it took a minimum of 1.6, 5.1, and 10 million generations for terrestrial mammal mass to increase 100-, and 1,000-, and 5,000-fold, respectively. Values for whales were down to half the length (i.e., 1.1, 3, and 5 million generations), perhaps due to the reduced mechanical constraints of living in an aquatic environment. When differences in generation time are considered, we find an exponential increase in maximum mammal body mass during the 35 million years following the Cretaceous-Paleogene (K-Pg) extinction event. Our results also indicate a basic asymmetry in macroevolution: very large decreases (such as extreme insular dwarfism) can happen at more than 10 times the rate of increases. Our findings allow more rigorous comparisons of microevolutionary and macroevolutionary patterns and processes.

  1. Isolation and ectopic expression of a bamboo MADS-box gene

    Institute of Scientific and Technical Information of China (English)

    TIAN Bo; CHEN Yongyan; YAN Yuanxin; LI Dezhu

    2005-01-01

    A cDNA named DlMADS18 was isolated from the young spikelets of the sweet bamboo, Dendrocalamus latiflorus by RACE. DNA sequence analysis showed that DlMADS18 was composed of full ORF and 3'UTR, but without 5′UTR. The cDNA contained 1039 nucleotides and encoded a putative protein of 249 amino acid residues. The gene displayed the structure of a typical plant MADS box gene, which consisted of an MADS domain, K domain, a short I region, and the C-terminal region. Phylogenetic analysis of plant MADS box genes based on amino acid sequences revealed that DlMADS18 was grouped into the AGAMOUS-LIKE 6 (AGL6)-like subfamily. It was most likely homologous to the OsMADS6 of rice (Oryza sativa), with 88% sequence identity for the entire amino acid sequences. The DlMADS18 also showed relatively high amino acid sequence identity (59%) to AGL6 of Arabidopsis thaliana. To study the functions of DlMADS18, DlMADS18 cDNA clone driven by the CaMV 35S promoter was transformed into Arabidopsis plants. Transgenic plants of DlMADS18 exhibited the phenotypes of curled leaves, dwarfism, and early flowering with clustered terminal flowers. These results indicated that DlMADS18 may probably be involved in controlling the flowering time of D. Latiflorus.

  2. Neuroimaging features of Cornelia de Lange syndrome.

    Science.gov (United States)

    Whitehead, Matthew T; Nagaraj, Usha D; Pearl, Phillip L

    2015-07-01

    Cornelia de Lange syndrome is a rare genetic disease characterized by distinctive facial dysmorphia and dwarfism. Multiple organ system involvement is typical. Various central nervous system (CNS) aberrations have been described in the pathology literature; however, the spectrum of neuroimaging manifestations is less well documented. To present neuroimaging findings from a series of eight patients with Cornelia de Lange syndrome. The CT/MR database at a single academic children's hospital was searched for the terms "Cornelia," "Brachmann" and "de Lange." The search yielded 18 exams from 16 patients. Two non-CNS and six exams without available images were excluded. Ten exams from eight patients were evaluated by a board-certified neuroradiologist. All patients had skull base dysplasia, most with an unusual coronal basioccipital cleft (7/8). All brain MR exams showed microcephaly, volume loss and gyral simplification (5/5). Six patients had an absent massa intermedia. Four patients had small globe anterior segments; three had optic pathway hypoplasia. Basilar artery fenestration was present in two patients; vertebrobasilar hypoplasia was present in one patient. The inner ear vestibules were dysplastic in two patients. One patient had pachymeningeal thickening. Spinal anomalies included scoliosis, segmentation anomalies, endplate irregularities, basilar invagination, foramen magnum stenosis and tethered spinal cord. Typical imaging manifestations of Cornelia de Lange syndrome include skull base dysplasia with coronal clival cleft, cerebral and brainstem volume loss, and gyral simplification. Membranous labyrinth dysplasia, anterior segment and optic pathway hypoplasia, basilar artery fenestration, absent massa intermedia and spinal anomalies may also be present.

  3. Phenotypic characteristics of hydrocephalus in stillborn Friesian foals.

    Science.gov (United States)

    Sipma, K D; Cornillie, P; Saulez, M N; Stout, T A E; Voorhout, G; Back, W

    2013-11-01

    Hydrocephalus is uncommon in horses. However, in recent years, it has become clear that the prevalence of hydrocephalus is greater in Friesian horses than in other breeds probably due to their limited gene pool. Before identification of candidate genes that predispose to the development of hydrocephalus in Friesian horses can be pursued, an in-depth, phenotypic, pathological description of the condition in Friesians would be of great benefit. Our study aimed to characterize the morphology of hydrocephalus in Friesian horses, to support further investigation of the genetic background of this condition. Four stillborn Friesian foals with hydrocephalus were examined macroscopically and microscopically and compared with 2 normal stillborn Friesian foals without hydrocephalus. In all clinical cases, tetraventricular and venous dilatations were observed, together with malformation of the petrosal bone and, as a result, narrowing of the jugular foramen. These observations suggest a communicative hydrocephalus with a diminished absorption of cerebrospinal fluid into the systemic circulation at the venous sinuses due to a distorted, nonfunctional jugular foramen. This type of hydrocephalus is also recognized in humans and dogs and has been linked genetically to chondrodysplasia; this has already been recognized in dwarfism, which is another monogenetic defect in Friesian horses.

  4. Mucopolysaccharidosis VI in a Siamese/short-haired European cat.

    Science.gov (United States)

    Macrì, B; Marino, F; Mazzullo, G; Trusso, A; De Maria, R; Amedeo, S; Divari, S; Castagnaro, M

    2002-10-01

    A 3-year-old Siamese/short-haired European cat was referred for clinical disease characterized by dwarfism, facial dysmorphia, paralysis, small and curled ears, corneal clouding and large areas of alopecia. X-ray examination showed multiple bone dysplasia. On the basis of clinical features a form of mucopolysaccharidosis was suspected. The cat, killed at the owner's request, presented several severe skeletal deformities such as long caudal limbs, enlarged thorax with sunken breastbone, vertebral ankylosis in many spinal segments and visceral involvement. Histologically, the cat showed diffuse vacuolization and enlargement of cells in cartilage, bone and visceral organs. Ultrastructurally, membrane-bound vacuoles were filled with fibrillar and fluffy-material or concentrically whorled lamellae. Arylsulphatase B activity was 3.24 nm/mg/h in the affected cat and 30.6 in a normal age-matched control (NC). The L-iduronidase activity was slightly increased. Quantitation of total glycosaminoglycans (GAGs) revealed a 4.5-fold increase in the affected cat as compared with NC, while electrophoretic run of specific GAGs [chondroitin sulphate (CA); hyaluronan (HA); heparan sulphate (HS); dermatan sulphate (DS); keratan sulphate (KS)] performed on a cellulose acetate sheet, showed a striking increase in the DS band. On densitometric analysis of the electrophoretic run stained with Alcian Blue 8GX, the absorption of DS was eight-fold increased as compared with NC. The clinical and morphological features, and the biochemical findings, were consistent with the diagnosis of feline mucopolysaccharidosis VI.

  5. Laron syndrome. First report from Greece.

    Science.gov (United States)

    Galli-Tsinopoulou, Assimina; Nousia-Arvanitakis, Sanda; Tsinopoulos, Ioannis; Bechlivanides, Christos; Shevah, Orit; Laron, Zvi

    2003-01-01

    Laron-type dwarfism is an autosomal recessive disorder caused by deletions or mutations of the growth hormone receptor gene. It is characterized by high circulating levels of growth hormone (GH) and low levels of insulin-like growth factor I (IGF-I). Patients are refractory to both endogenous and exogenous GH, and present severe growth retardation and obesity. Therapy with recombinant human insulin-like growth factor-I (rhIGF-I) accelerates linear growth. We describe a 2-year old girl with Laron syndrome, who presented with postnatal growth failure and hypoglycaemic seizures. Her evaluation disclosed high GH values during a glucagon test (peak GH value 170 ng/ml) and very low IGF I value (0.1 ng/ml) with no rise following GH administration. The growth velocity improved considerably with the administration of IGF I. Molecular analysis showed a heterozygous mutation on exon 4 of the GH receptor gene, inherited from the mother, a rather puzzling finding considering the clinical findings in mother and infant. This case constitutes the first report of Laron syndrome from Greece.

  6. IGF-1 and insulin as growth hormones.

    Science.gov (United States)

    Laron, Zvi

    2004-01-01

    IGF-1 generated in the liver is the anabolic effector and linear growth promoting hormone of the pituitary growth hormone (GH). This is evidenced by dwarfism in states of congenital IGF-1 deficiency, Igf1 gene mutation/deletions or knockouts, and in Laron syndrome (LS), due to GH receptor gene mutations/deletions or IGF-1 receptor blocking. In a positive way, daily IGF-1 administration to stunted patients with LS or hGH gene deletion accelerates linear growth velocity. IGF-1 acts on the proliferative cells of the epiphyseal cartilage. IGF-1 also induces organ and tissue growth; its absence causing organomicria. Insulin shares a common ancestry with IGF-1 and with 45% amino acid homology, as well as very close relationships in the structure of its receptors and post-receptor cascade, also acts as a growth hormone. It has protein anabolic activity and stimulates IGF-1 synthesis. Pancreas agenesis causes short babies, and obese children with hyperinsulinism, with or without pituitary GH, have an accelerated growth rate and skeletal maturation; so do babies with macrosomia. Whether the insulin growth effect is direct, or mediated by IGF-1 or leptin is controversial.

  7. Fifty seven years of follow-up of the Israeli cohort of Laron Syndrome patients-From discovery to treatment.

    Science.gov (United States)

    Laron, Zvi; Kauli, Rivka

    2016-06-01

    Clinical and laboratory investigations of dwarfed children newly Jewish immigrants from Yemen and Middle East and who resembled patients with isolated growth hormone deficiency were started by our group in 1958. In 1963 when we found that they have high serum levels of hGH, we knew that we had discovered a new disease of primary GH insensitivity. It was subsequently coined Laron Syndrome (LS, OMIM #262500). The etiopathogenesis was disclosed by 2 liver biopsies demonstrating a defect in the GH receptor. Subsequent investigations demonstrated deletions or mutations in the GHR gene. The defect lead to an inability of IGF-I generation, resulting in severe dwarfism, obesity, and other morphologic and biochemical pathologies due to IGF-I deficiency. With the biosynthesis of IGF-I in 1986, therapeutic trials started. Following closely our cohort of 69 patients with LS enabled us to study its features in untreated and IGF-I treated patients. This syndrome proved to be a unique model to investigate the effects of IGF-I dissociated from GH stimulation. In recent studies we found that homozygous patients for the GHR mutations are protected lifelong from developing malignancies, opening new directions of research.

  8. Discoid Meniscus Associated With Achondroplasia.

    Science.gov (United States)

    Hoernschemeyer, Daniel G; Atanda, Alfred; Dean-Davis, Ellen; Gupta, Sumit K

    2016-05-01

    Achondroplasia is the most common skeletal dysplasia. This form of dwarfism is caused by a point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene, leading to inhibition of endochondral ossification for these patients. This results in a normal trunk height but shortened limbs. The discoid meniscus may be an important associated finding to better understand the common complaints of leg pain for these patients. Although the incidence for a discoid meniscus is between 3% and 5% for the general population, it is unknown with achondroplasia. This case series includes 4 patients, with ages ranging from adolescence to early adulthood, with symptoms of knee pain that were not attributable to some of the more common findings seen in this patient population. Typically, patients with achondroplasia who experience knee pain are evaluated for more common and well-known etiologies such as genu varum, ligamentous instability, and neurogenic claudication. However, the authors propose that symptomatic discoid lateral meniscus should be added to the differential diagnosis for lower-extremity pain in the achondroplasia population. A thorough history and physical examination, in combination with magnetic resonance imaging, can aid in making the diagnosis. Treatment with arthroscopic debridement, saucerization of the meniscus, and repair for unstable injuries has yielded good outcomes for this patient population. [Orthopedics. 2016; 39(3):e498-e503.]. Copyright 2016, SLACK Incorporated.

  9. A mouse model for achondroplasia produced by targeting fibroblast growth factor receptor 3

    Science.gov (United States)

    Wang, Yingcai; Spatz, Michal K.; Kannan, Karuppiah; Hayk, Hovhannisyan; Avivi, Aaron; Gorivodsky, Marat; Pines, Mark; Yayon, Avner; Lonai, Peter; Givol, David

    1999-01-01

    Achondroplasia, the most common form of dwarfism in man, is a dominant genetic disorder caused by a point mutation (G380R) in the transmembrane region of fibroblast growth factor receptor 3 (FGFR3). We used gene targeting to introduce the human achondroplasia mutation into the murine FGFR3 gene. Heterozygotes for this point mutation that carried the neo cassette were normal whereas neo+ homozygotes had a phenotype similar to FGFR3-deficient mice, exhibiting bone overgrowth. This was because of interference with mRNA processing in the presence of the neo cassette. Removal of the neo selection marker by Cre/loxP recombination yielded a dominant dwarf phenotype. These mice are distinguished by their small size, shortened craniofacial area, hypoplasia of the midface with protruding incisors, distorted brain case with anteriorly shifted foramen magnum, kyphosis, and narrowed and distorted growth plates in the long bones, vertebrae, and ribs. These experiments demonstrate that achondroplasia results from a gain-of-FGFR3-function leading to inhibition of chondrocyte proliferation. These achondroplastic dwarf mice represent a reliable and useful model for developing drugs for potential treatment of the human disease. PMID:10200283

  10. Knock-in human FGFR3 achondroplasia mutation as a mouse model for human skeletal dysplasia

    Science.gov (United States)

    Lee, Yi-Ching; Song, I-Wen; Pai, Ya-Ju; Chen, Sheng-De; Chen, Yuan-Tsong

    2017-01-01

    Achondroplasia (ACH), the most common genetic dwarfism in human, is caused by a gain-of function mutation in fibroblast growth factor receptor 3 (FGFR3). Currently, there is no effective treatment for ACH. The development of an appropriate human-relevant model is important for testing potential therapeutic interventions before human clinical trials. Here, we have generated an ACH mouse model in which the endogenous mouse Fgfr3 gene was replaced with human FGFR3G380R (FGFR3ACH) cDNA, the most common mutation in human ACH. Heterozygous (FGFR3ACH/+) and homozygous (FGFR3ACH/ACH) mice expressing human FGFR3G380R recapitulate the phenotypes observed in ACH patients, including growth retardation, disproportionate shortening of the limbs, round head, mid-face hypoplasia at birth, and kyphosis progression during postnatal development. We also observed premature fusion of the cranial sutures and low bone density in newborn FGFR3G380R mice. The severity of the disease phenotypes corresponds to the copy number of activated FGFR3G380R, and the phenotypes become more pronounced during postnatal skeletal development. This mouse model offers a tool for assessing potential therapeutic approaches for skeletal dysplasias related to over-activation of human FGFR3, and for further studies of the underlying molecular mechanisms. PMID:28230213

  11. Neurosurgical implications of achondroplasia.

    Science.gov (United States)

    King, James A J; Vachhrajani, Shobhan; Drake, James M; Rutka, James T

    2009-10-01

    Achondroplasia is the most common form of human short-limbed dwarfism. The pediatric neurosurgeon is frequently required to treat children with achondroplasia who have hydrocephalus, cervicomedullary compression (CMD), and spinal canal stenosis. Accordingly, the authors have reviewed the experience of neurosurgery in children with achondroplasia at The Hospital for Sick Children. The medical records and neurosurgery database at The Hospital for Sick Children were searched to identify all children with achondroplasia who underwent at least 1 neurosurgical procedure between 1956 and the present. Twenty-nine children with achondroplasia underwent 85 surgical procedures: 52 for CSF diversion in 12 patients, 20 for CMD in 18 patients, 8 for spinal disorders in 4 patients, and 5 for miscellaneous purposes in 4 patients. The CSF shunts were placed almost exclusively before 1990 and were associated with a significant number of complications. Patients undergoing CMD did very well, with only 1 patient failing to improve clinically. This review provides a historical perspective on the evolution of treatment of pediatric patients with achondroplasia. The use of CSF diversion procedures, formerly fraught with complications, is now rare following the realization of the natural history of CSF space enlargement in these patients. Cervicomedullary compression is more commonly recognized due to better imaging. Central apnea is now better detected by routine sleep studies. Spine surgery, although rare, requires evaluation of both spinal stenosis and instability. These patients are best evaluated by a multidisciplinary team.

  12. Meckel's and condylar cartilages anomalies in achondroplasia result in defective development and growth of the mandible.

    Science.gov (United States)

    Biosse Duplan, Martin; Komla-Ebri, Davide; Heuzé, Yann; Estibals, Valentin; Gaudas, Emilie; Kaci, Nabil; Benoist-Lasselin, Catherine; Zerah, Michel; Kramer, Ina; Kneissel, Michaela; Porta, Diana Grauss; Di Rocco, Federico; Legeai-Mallet, Laurence

    2016-07-15

    Activating FGFR3 mutations in human result in achondroplasia (ACH), the most frequent form of dwarfism, where cartilages are severely disturbed causing long bones, cranial base and vertebrae defects. Because mandibular development and growth rely on cartilages that guide or directly participate to the ossification process, we investigated the impact of FGFR3 mutations on mandibular shape, size and position. By using CT scan imaging of ACH children and by analyzing Fgfr3(Y367C/+) mice, a model of ACH, we show that FGFR3 gain-of-function mutations lead to structural anomalies of primary (Meckel's) and secondary (condylar) cartilages of the mandible, resulting in mandibular hypoplasia and dysmorphogenesis. These defects are likely related to a defective chondrocyte proliferation and differentiation and pan-FGFR tyrosine kinase inhibitor NVP-BGJ398 corrects Meckel's and condylar cartilages defects ex vivo. Moreover, we show that low dose of NVP-BGJ398 improves in vivo condyle growth and corrects dysmorphologies in Fgfr3(Y367C/+) mice, suggesting that postnatal treatment with NVP-BGJ398 mice might offer a new therapeutic strategy to improve mandible anomalies in ACH and others FGFR3-related disorders. © The Author 2016. Published by Oxford University Press.

  13. Achondroplasia: from genotype to phenotype.

    Science.gov (United States)

    Richette, Pascal; Bardin, Thomas; Stheneur, Chantal

    2008-03-01

    This review focuses on the rheumatological features of achondroplasia, which is the most common skeletal dysplasia and the most frequent cause of short-limbed dwarfism. It is inherited in an autosomal dominant manner but results in the majority of cases of de novo mutations. The disease is related to a mutation in the fibroblast growth factor receptor-3 (FGFR3) gene encoding one member of the FGFR subfamily of tyrosine kinase receptors, which results in constitutive activation of the receptor. Biochemical studies of FGFR3 combined with experiments in knock-out mice have demonstrated that FGFR3 is a negative regulator of chondrocytes proliferation and differentiation in growth plate. This mutation induces a disturbance of endochondral bone formation. The diagnosis of achondroplasia is based on typical clinical and radiological features including short stature, macrocephaly with frontal bossing, midface hypoplasia and rhizomelic shortening of the limbs. The most common rheumatological complications of achondroplasia are medullar and radicular compressions due to spinal stenosis and deformities of the lower limbs. Current treatment and future therapies are discussed.

  14. Application of nuclear energy to agriculture. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Moh, C.C.

    1976-06-30

    The following research projects in radiation botany were conducted: mutation breeding of beans and cassava; biological response of coffee plants; and radiosensitivity of tropical plants. In the field of entomology experiments were conducted on radiosterilization of the Mediterranean fruit fly, the coffee leaf miner, the torsalo and the meliaceous shootborer. The following research projects in plant physiology were conducted: physiology of cassava plants; effects of temperature on germination of cacao seeds; physiology of cacao seeds; sulfur metabolism using /sup 35/S; diseases and parasites of banana fruits; the mechanism controlling dwarfism in a radioinduced single gene bean mutant; and the use of wetting agents in foliar nutrition. The following research projects in soil chemistry were conducted: acidity and cation movement in tropical soils; phosphate in soils of the humid tropics; movement, adsorption and desorption of sulfates; free iron and aluminium oxides in tropical soils; mineralization of organic nitrogen in soils on volcanic materials; soil chemical properties of recent volcanic ash; and spatial distribution of the absorbing roots in coffee. Discussions are presented of installation of radiation facilities and collection of rainfall for fallout analysis. (HLW)

  15. Transgenic Wuzhishan minipigs designed to express a dominant-negative porcine growth hormone receptor display small stature and a perturbed insulin/IGF-1 pathway.

    Science.gov (United States)

    Li, Feida; Li, Yong; Liu, Huan; Zhang, Xingju; Liu, Chuxin; Tian, Kai; Bolund, Lars; Dou, Hongwei; Yang, Wenxian; Yang, Huanming; Staunstrup, Nicklas Heine; Du, Yutao

    2015-12-01

    Growth hormone (GH) is an anabolic mitogen with widespread influence on cellular growth and differentiation as well as on glucose and lipid metabolism. GH binding to the growth hormone receptor (GHR) on hepatocytes prompts expression of insulin growth factor I (IGF-1) involved in nutritionally induced compensatory hyperplasia of pancreatic β-cell islets and insulin release. A prolonged hyperactivity of the IGF-1/insulin axis in the face of insulinotropic nutrition, on the other hand, can lead to collapse of the pancreatic islets and glucose intolerance. Individuals with Laron syndrome carry mutations in the GHR gene resulting in severe congenital IGF-1 deficiency and elevated GH serum levels leading to short stature as well as perturbed lipid and glucose metabolism. However, these individuals enjoy a reduced prevalence of acne, cancer and possibly diabetes. Minipigs have become important biomedical models for human conditions due to similarities in organ anatomy, physiology, and metabolism relative to humans. The purpose of this study was to generate transgenic Wuzhishan minipigs by handmade cloning with impaired systemic GHR activity and assess their growth profile and glucose metabolism. Transgenic minipigs featuring overexpression of a dominant-negative porcine GHR (GHR(dm)) presented postnatal growth retardation and proportionate dwarfism. Molecular changes included elevated GH serum levels and mild hyperglycemia. We believe that this model may prove valuable in the study of GH functions in relation to cancer, diabetes and longevity.

  16. Langerhans' Cell Histiocytosis (Histiocytosis X) of the Temporal Bone

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objectives Langerhans' Cell histiocytosis (LCH) is a rare disease, which remains poorly understood and whose cellular origin remains unknown. To increase understanding of temporal bone LCH, it is necessary to study recent advances in the diagnosis and treatment of this disease. Methods The long term(5 to 30 years) results of 21 temporal bone LCH cases treated between 1973 and 2003 were reviewed. Surgery, radiotherapy,pharmacologic therapy or a combination of these treatments were employed in these cases. Results Eighteen patients were cured (18/21, 85%). Six patients developed residual diabetes insipidus (DI) and dwarfism (28%).Three patients died (14%). Conclusions The Alessi classification system for LCH based on the extent of disease accurately predicts prognosis and is a useful guide in selecting treatment methodologies. X-ray, computed tomography and magnetic resonance imaging have proved useful in defining the extent of osseous and soft tissue diseases. Diagnosis of LCH is based on clinical presentations, radiographic findings and histopathological results.Surgery and radiotherapy are the main treatment modalities. Pharmacologic therapy should be used in patients with aggressive, disseminate, and refractory lesions. LCH has a predilection for children and prognosis depends on age and extent of vital organ involvement.

  17. Isolation and Genomic Characterization of a Duck-Origin GPV-Related Parvovirus from Cherry Valley Ducklings in China.

    Directory of Open Access Journals (Sweden)

    Hao Chen

    Full Text Available A newly emerged duck parvovirus, which causes beak atrophy and dwarfism syndrome (BADS in Cherry Valley ducks, has appeared in Northern China since March 2015. To explore the genetic diversity among waterfowl parvovirus isolates, the complete genome of an identified isolate designated SDLC01 was sequenced and analyzed in the present study. Genomic sequence analysis showed that SDLC01 shared 90.8%-94.6% of nucleotide identity with goose parvovirus (GPV isolates and 78.6%-81.6% of nucleotide identity with classical Muscovy duck parvovirus (MDPV isolates. Phylogenetic analysis of 443 nucleotides (nt of the fragment A showed that SDLC01 was highly similar to a mule duck isolate (strain D146/02 and close to European GPV isolates but separate from Asian GPV isolates. Analysis of the left inverted terminal repeat regions revealed that SDLC01 had two major segments deleted between positions 160-176 and 306-322 nt compared with field GPV and MDPV isolates. Phylogenetic analysis of Rep and VP1 encoded by two major open reading frames of parvoviruses revealed that SDLC01 was distinct from all GPV and MDPV isolates. The viral pathogenicity and genome characterization of SDLC01 suggest that the novel GPV (N-GPV is the causative agent of BADS and belongs to a distinct GPV-related subgroup. Furthermore, N-GPV sequences were detected in diseased ducks by polymerase chain reaction and viral proliferation was demonstrated in duck embryos and duck embryo fibroblast cells.

  18. Molecular detection of chicken parvovirus in broilers with enteric disorders presenting curving of duodenal loop, pancreatic atrophy, and mesenteritis.

    Science.gov (United States)

    Nuñez, L F N; Sá, L R M; Parra, S H S; Astolfi-Ferreira, C S; Carranza, C; Ferreira, A J P

    2016-04-01

    Enteric disorders are an important cause of economic losses in broiler chickens worldwide. Several agents have been associated with enteric problems, such as viruses, bacteria, and parasites. In this study, broiler chickens showing signs of enteric disorders were subjected to molecular diagnosis for several viral agents and also for pathological examination for elucidating this problem. Thus, the chickens were screened for avian nephritis virus (ANV), chicken astrovirus (CAstV), avian rotavirus (ArtV), avian reovirus (AReoV), infectious bronchitis virus (IBV), fowl adenovirus group I (FAdV-1), and chicken parvovirus (ChPV). Postmortem examinations revealed a curving of the duodenal loop (J-like appearance) and intestines filled with liquid and gaseous content. Histopathological analysis of the duodenal loop showed pancreatic atrophy, acute mesenteritis, and enteritis. PCR results showed that ChPV was the sole viral agent detected in samples with lesions such as the curved duodenal loop and pancreatic atrophy. Molecular characterization of the nucleotide and deduced amino acid sequences revealed a high similarity with other strains of ChPV from Brazil, Canada, United States, Europe, and Asia. These findings suggest an association between ChPV and the development of enteritis, pancreatitis, and pancreatic atrophy, which may lead to curling of the duodenal loop. Together, these alterations may disrupt the normal functioning of the digestive system, diminishing digestion and the absorption of dietary nutrients and consequently leading to reduced weight gain, flock impairment, dwarfism, and an elevated feed conversion rate.

  19. SLC39A8 Deficiency: A Disorder of Manganese Transport and Glycosylation.

    Science.gov (United States)

    Park, Julien H; Hogrebe, Max; Grüneberg, Marianne; DuChesne, Ingrid; von der Heiden, Ava L; Reunert, Janine; Schlingmann, Karl P; Boycott, Kym M; Beaulieu, Chandree L; Mhanni, Aziz A; Innes, A Micheil; Hörtnagel, Konstanze; Biskup, Saskia; Gleixner, Eva M; Kurlemann, Gerhard; Fiedler, Barbara; Omran, Heymut; Rutsch, Frank; Wada, Yoshinao; Tsiakas, Konstantinos; Santer, René; Nebert, Daniel W; Rust, Stephan; Marquardt, Thorsten

    2015-12-03

    SLC39A8 is a membrane transporter responsible for manganese uptake into the cell. Via whole-exome sequencing, we studied a child that presented with cranial asymmetry, severe infantile spasms with hypsarrhythmia, and dysproportionate dwarfism. Analysis of transferrin glycosylation revealed severe dysglycosylation corresponding to a type II congenital disorder of glycosylation (CDG) and the blood manganese levels were below the detection limit. The variants c.112G>C (p.Gly38Arg) and c.1019T>A (p.Ile340Asn) were identified in SLC39A8. A second individual with the variants c.97G>A (p.Val33Met) and c.1004G>C (p.Ser335Thr) on the paternal allele and c.610G>T (p.Gly204Cys) on the maternal allele was identified among a group of unresolved case subjects with CDG. These data demonstrate that variants in SLC39A8 impair the function of manganese-dependent enzymes, most notably β-1,4-galactosyltransferase, a Golgi enzyme essential for biosynthesis of the carbohydrate part of glycoproteins. Impaired galactosylation leads to a severe disorder with deformed skull, severe seizures, short limbs, profound psychomotor retardation, and hearing loss. Oral galactose supplementation is a treatment option and results in complete normalization of glycosylation. SLC39A8 deficiency links a trace element deficiency with inherited glycosylation disorders.

  20. Cockayne syndrome group B (CSB) protein: at the crossroads of transcriptional networks.

    Science.gov (United States)

    Vélez-Cruz, Renier; Egly, Jean-Marc

    2013-01-01

    Cockayne syndrome (CS) is a rare genetic disorder characterized by a variety of growth and developmental defects, photosensitivity, cachectic dwarfism, hearing loss, skeletal abnormalities, progressive neurological degeneration, and premature aging. CS arises due to mutations in the CSA and CSB genes. Both gene products are required for the transcription-coupled (TC) branch of the nucleotide excision repair (NER) pathway, however, the severe phenotype of CS patients is hard to reconcile with a sole defect in TC-NER. Studies using cells from patients and mouse models have shown that the CSB protein is involved in a variety of cellular pathways and plays a major role in the cellular response to stress. CSB has been shown to regulate processes such as the transcriptional recovery after DNA damage, the p53 transcriptional response, the response to hypoxia, the response to insulin-like growth factor-1 (IGF-1), transactivation of nuclear receptors, transcription of housekeeping genes and the transcription of rDNA. Some of these processes are also affected in combined XP/CS patients. These new advances in the function(s) of CSB shed light onto the etiology of the clinical features observed in CS patients and could potentially open therapeutic avenues for these patients in the future. Moreover, the study of CS could further our knowledge of the aging process.

  1. A single nucleotide mutation in Nppc is associated with a long bone abnormality in lbab mice

    Directory of Open Access Journals (Sweden)

    Roe Bruce A

    2007-04-01

    Full Text Available Abstract Background The long bone abnormality (lbab mouse is a new autosomal recessive mutant characterized by overall smaller body size with proportionate dwarfing of all organs and shorter long bones. Previous linkage analysis has located the lbab mutation on chromosome 1 between the markers D1Mit9 and D1Mit488. Results A genome-based positional approach was used to identify a mutation associated with lbab disease. A total of 122 genes and expressed sequence tags at the lbab region were screened for possible mutation by using genomic DNA from lbabl/lbab, lbab/+, and +/+ B6 mice and high throughput temperature gradient capillary electrophoresis. A sequence difference was identified in one of the amplicons of gene Nppc between lbab/lbab and +/+ mice. One-step reverse transcriptase polymerase chain reaction was performed to validate the difference of Nppc in different types of mice at the mRNA level. The mutation of Nppc was unique in lbab/lbab mice among multiple mouse inbred strains. The mutation of Nppc is co-segregated with lbab disease in 200 progenies produced from heterozygous lbab/+ parents. Conclusion A single nucleotide mutation of Nppc is associated with dwarfism in lbab/lbab mice. Current genome information and technology allow us to efficiently identify single nucleotide mutations from roughly mapped disease loci. The lbab mouse is a useful model for hereditary human achondroplasia.

  2. Overexpression of the phytochrome B gene from Arabidopsis thaliana increases plant growth and yield of cotton (Gossypium hirsutum)

    Institute of Scientific and Technical Information of China (English)

    Abdul Qayyum RAO; Muhammad IRFAN; Zafar SALEEM; Idrees Ahmad NASIR; Sheikh RIAZUDDIN; Tayyab HUSNAIN

    2011-01-01

    The phytochrome B (PHYB) gene of Arabidopsis thaliana was introduced into cotton through Agrobacterium tumefaciens. Integration and expression of PHYB gene in cotton plants were confirmed by molecular evidence.Messenger RNA (mRNA) expression in one of the transgenic lines, QCC11, was much higher than those of control and other transgenic lines. Transgenic cotton plants showed more than a two-fold increase in photosynthetic rate and more than a four-fold increase in transpiration rate and stomatal conductance. The increase in photosynthetic rate led to a 46% increase in relative growth rate and an 18% increase in net assimilation rate. Data recorded up to two generations,both in the greenhouse and in the field, revealed that overexpression ofArabidopsis thaliana PHYB gene in transgeniccotton plants resulted in an increase in the production of cotton by improving the cotton plant growth, with 35% more yield. Moreover, the presence of the Arabidopsis thaliana PHYB gene caused pleiotropic effects like semi-dwarfism,decrease in apical dominance, and increase in boll size.

  3. Virtual MRI endoscopy of the intracranial cerebrospinal fluid spaces

    Energy Technology Data Exchange (ETDEWEB)

    Shigematsu, Y.; Korogi, Y.; Hirai, T. [Kumamoto Univ. (Japan). Dept. of Radiology; Okuda, T.; Ikushima, I.; Sugahara, T.; Liang, L.; Ge, Y.; Takahashi, M.

    1998-10-01

    We used constructive interference in steady state (CISS) 3D Fourier transform (3DFT) MRI data sets to obtain three-dimensional (3D) virtual MRI endoscopic views of the intracranial cerebrospinal fluid (CSF) spaces, processing them with a commercially available perspective endoscopic algorithm. We investigated the potential of the intracranial virtual MRI endoscopy applied to visualisation of the pathology in 13 patients with surgically confirmed trigeminal neuralgia (3), hemifacial spasm (3), acoustic neuroma (3), suprasellar germinoma (1), Langerhans cell histiocytosis (1), lateral ventricle nodules (1) and pituitary dwarfism (1). All images were acquired using a 1.5-T imager employing a circular polarised head coil. The CISS-3DFT data sets were transferred to a workstation for processing with the perspective endoscopic algorithm. Postprocessing for virtual MRI endoscopy was possible for all data sets. The lesions in 12 patients, and their complex anatomical relationships with the surrounding structures, were well seen on the 3D images. A small acoustic neuroma in the internal auditory meatus was not seen using virtual endoscopy. Although virtual MRI endoscopy has limitations, it provides 3D images which cannot be acquired using any other procedure. (orig.) With 6 figs., 16 refs.

  4. Clinical and functional characterization of a patient carrying a compound heterozygous pericentrin mutation and a heterozygous IGF1 receptor mutation.

    Science.gov (United States)

    Müller, Eva; Dunstheimer, Desiree; Klammt, Jürgen; Friebe, Daniela; Kiess, Wieland; Kratzsch, Jürgen; Kruis, Tassilo; Laue, Sandy; Pfäffle, Roland; Wallborn, Tillmann; Heidemann, Peter H

    2012-01-01

    Intrauterine and postnatal longitudinal growth is controlled by a strong genetic component that regulates a complex network of endocrine factors integrating them with cellular proliferation, differentiation and apoptotic processes in target tissues, particularly the growth centers of the long bones. Here we report on a patient born small for gestational age (SGA) with severe, proportionate postnatal growth retardation, discreet signs of skeletal dysplasia, microcephaly and moyamoya disease. Initial genetic evaluation revealed a novel heterozygous IGF1R p.Leu1361Arg mutation affecting a highly conserved residue with the insulin-like growth factor type 1 receptor suggestive for a disturbance within the somatotropic axis. However, because the mutation did not co-segregate with the phenotype and functional characterization did not reveal an obvious impairment of the ligand depending major IGF1R signaling capabilities a second-site mutation was assumed. Mutational screening of components of the somatotropic axis, constituents of the IGF signaling system and factors involved in cellular proliferation, which are described or suggested to provoke syndromic dwarfism phenotypes, was performed. Two compound heterozygous PCNT mutations (p.[Arg585X];[Glu1774X]) were identified leading to the specification of the diagnosis to MOPD II. These investigations underline the need for careful assessment of all available information to derive a firm diagnosis from a sequence aberration.

  5. Clinical and functional characterization of a patient carrying a compound heterozygous pericentrin mutation and a heterozygous IGF1 receptor mutation.

    Directory of Open Access Journals (Sweden)

    Eva Müller

    Full Text Available Intrauterine and postnatal longitudinal growth is controlled by a strong genetic component that regulates a complex network of endocrine factors integrating them with cellular proliferation, differentiation and apoptotic processes in target tissues, particularly the growth centers of the long bones. Here we report on a patient born small for gestational age (SGA with severe, proportionate postnatal growth retardation, discreet signs of skeletal dysplasia, microcephaly and moyamoya disease. Initial genetic evaluation revealed a novel heterozygous IGF1R p.Leu1361Arg mutation affecting a highly conserved residue with the insulin-like growth factor type 1 receptor suggestive for a disturbance within the somatotropic axis. However, because the mutation did not co-segregate with the phenotype and functional characterization did not reveal an obvious impairment of the ligand depending major IGF1R signaling capabilities a second-site mutation was assumed. Mutational screening of components of the somatotropic axis, constituents of the IGF signaling system and factors involved in cellular proliferation, which are described or suggested to provoke syndromic dwarfism phenotypes, was performed. Two compound heterozygous PCNT mutations (p.[Arg585X];[Glu1774X] were identified leading to the specification of the diagnosis to MOPD II. These investigations underline the need for careful assessment of all available information to derive a firm diagnosis from a sequence aberration.

  6. Growth factors, aging and age-related diseases.

    Science.gov (United States)

    Balasubramanian, Priya; Longo, Valter D

    2016-06-01

    Simple organisms including yeast and flies with mutations in the IGF-1 and Tor-S6K pathways are dwarfs, are highly protected from toxins, and survive up to 3 times longer. Similarly, dwarf mice with deficiencies in the growth hormone-IGF-I axis are also long lived and protected from diseases. We recently reported that humans with Growth Hormone Receptor Deficiency (GHRD) rarely develop cancer or diabetes. These findings are in agreement with the effect of defects in the Tor-S6K pathways in causing dwarfism and protection of DNA. Because protein restriction reduces both GHR-IGF-1 axis and Tor-S6K activity, we examined links between protein intake, disease, and mortality in over 6000 US subjects in the NHANES CDC database. Respondents aged 50-65 reporting a high protein intake displayed an increase in IGF-I levels, a 75% increased risk of overall mortality and a 3-4 fold increased risk of cancer mortality in agreement with findings in mouse experiments. These studies point to a conserved link between proteins and amino acids, GHR-IGF-1/insulin, Tor-S6k signaling, aging, and diseases.

  7. Encephalopathy with calcifications of the basal ganglia in children. A reappraisal of Fahr's syndrome with respect to 14 new cases.

    Science.gov (United States)

    Billard, C; Dulac, O; Bouloche, J; Echenne, B; Lebon, P; Motte, J; Robain, O; Santini, J J

    1989-02-01

    Calcifications of the basal ganglia are described under the heading of "Fahr's syndrome". The clinical pattern is variable and the syndrome may be sporadic or familial. This study describes a personal series of 14 cases of encephalopathy with calcification of the basal ganglia and reviews the literature cases. A four-group classification is proposed. The first group includes encephalopathy, microcephaly, dwarfism, retinal degeneration or optic atrophy, symmetrical patchy demyelination with calcifications and probable autosomal recessive inheritance. Some cases have an early onset, a rapid evolution. Others have a later onset, longer course and retinal degeneration. In the second group, the children suffer from a congenital encephalopathy or a cerebral palsy without clear deterioration, without short stature, ocular impairment or persistent CSF abnormalities. This group has not been reported in the literature. The cases do not seem to be genetic. The precise cause in unknown but a sporadic non progressive anoxo-ischemic, or viral prenatal disease is suggested. In the third group, the association of encephalopathy, microcephaly, and persistent CSF lymphocytosis, has a high recurrence rate. The pathogenesis is still a matter of dispute. The fourth group is characterized by autosomal dominant calcifications of the basal ganglia with or without neurological abnormalities. Finally calcium metabolism disorders and mitochondrial encephalomyopathy may be associated with calcifications of the basal ganglia.

  8. Molecular and physiological changes in response to salt stress in Citrus macrophylla W plants overexpressing Arabidopsis CBF3/DREB1A.

    Science.gov (United States)

    Alvarez-Gerding, Ximena; Espinoza, Carmen; Inostroza-Blancheteau, Claudio; Arce-Johnson, Patricio

    2015-07-01

    Plant stress induced by high salinity has leading to an important reduction in crop yields. Due to their tropical origin, citrus fruits are highly sensitive to salts. Rootstocks are the root system of fruit trees, regulating ion uptake and transport to the canopy. Therefore, increasing their salt tolerance could improve the salt tolerance of the fruit tree. For this, we genetically-transformed an important rootstock for lemon, Citrus macrophylla W, to constitutively express the CBF3/DREB1A gene from Arabidopsis, a well-studied salinity tolerance transcription factor. Transgenic lines showed normal size, with no dwarfism. Under salt stress, some transgenic lines showed greater growth, similar accumulation of chloride and sodium in the leaves and better stomatal conductance, in comparison to wild-type plants. Quantitative real-time analyses showed a similar expression of several CBF3/DREB1A target genes, such as COR15A, LEA 4/5, INV, SIP1, P5CS, GOLS, ADC2 and LKR/SDH, in transgenic lines and wild type plants, with the exception of INV that shows increased expression in line 4C15. Under salt stress, all measured transcript increased in both wild type and transgenics lines, with the exception of INV. Altogether, these results suggest a higher salt tolerance of transgenic C. macrophylla plants induced by the overexpression of AtCBF3/DREB1A.

  9. No skeletal dysplasia in the Nariokotome boy KNM-WT 15000 (Homo erectus)--a reassessment of congenital pathologies of the vertebral column.

    Science.gov (United States)

    Schiess, Regula; Haeusler, Martin

    2013-03-01

    The Nariokotome boy skeleton KNM-WT 15000 is the most complete Homo erectus fossil and therefore is key for understanding human evolution. Nevertheless, since Latimer and Ohman (2001) reported on severe congenital pathology in KNM-WT 15000, it is questionable whether this skeleton can still be used as reference for Homo erectus skeletal biology. The asserted pathologies include platyspondylic and diminutive vertebrae implying a disproportionately short stature; spina bifida; condylus tertius; spinal stenosis; and scoliosis. Based on this symptom complex, the differential diagnosis of spondyloepiphyseal dysplasia tarda, an extremely rare form of skeletal dysplasia, has been proposed. Yet, our reanalysis of these pathologies shows that the shape of the KNM-WT 15000 vertebrae matches that of normal modern human adolescents. The vertebrae are not abnormally flat, show no endplate irregularities, and thus are not platyspondylic. As this is the hallmark of spondyloepiphyseal dysplasia tarda and related forms of skeletal dysplasia, the absence of platyspondyly refutes axial dysplasia and disproportionate dwarfism. Furthermore, we neither found evidence for spina bifida occulta nor manifesta, whereas the condylus tertius, a developmental anomaly of the cranial base, is not related to skeletal dysplasias. Other fossils indicate that the relatively small size of the vertebrae and the narrow spinal canal are characteristics of early hominins rather than congenital pathologies. Except for the recently described signs of traumatic lumbar disc herniation, the Nariokotome boy fossil therefore seems to belong to a normal Homo erectus youth without pathologies of the axial skeleton. Copyright © 2013 Wiley Periodicals, Inc.

  10. The maximum rate of mammal evolution

    Science.gov (United States)

    Evans, Alistair R.; Jones, David; Boyer, Alison G.; Brown, James H.; Costa, Daniel P.; Ernest, S. K. Morgan; Fitzgerald, Erich M. G.; Fortelius, Mikael; Gittleman, John L.; Hamilton, Marcus J.; Harding, Larisa E.; Lintulaakso, Kari; Lyons, S. Kathleen; Okie, Jordan G.; Saarinen, Juha J.; Sibly, Richard M.; Smith, Felisa A.; Stephens, Patrick R.; Theodor, Jessica M.; Uhen, Mark D.

    2012-01-01

    How fast can a mammal evolve from the size of a mouse to the size of an elephant? Achieving such a large transformation calls for major biological reorganization. Thus, the speed at which this occurs has important implications for extensive faunal changes, including adaptive radiations and recovery from mass extinctions. To quantify the pace of large-scale evolution we developed a metric, clade maximum rate, which represents the maximum evolutionary rate of a trait within a clade. We applied this metric to body mass evolution in mammals over the last 70 million years, during which multiple large evolutionary transitions occurred in oceans and on continents and islands. Our computations suggest that it took a minimum of 1.6, 5.1, and 10 million generations for terrestrial mammal mass to increase 100-, and 1,000-, and 5,000-fold, respectively. Values for whales were down to half the length (i.e., 1.1, 3, and 5 million generations), perhaps due to the reduced mechanical constraints of living in an aquatic environment. When differences in generation time are considered, we find an exponential increase in maximum mammal body mass during the 35 million years following the Cretaceous–Paleogene (K–Pg) extinction event. Our results also indicate a basic asymmetry in macroevolution: very large decreases (such as extreme insular dwarfism) can happen at more than 10 times the rate of increases. Our findings allow more rigorous comparisons of microevolutionary and macroevolutionary patterns and processes. PMID:22308461

  11. Genetic Analysis and Mapping of the Dominant Dwarfing Gene D-53 in Rice

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The dwarfing gene D-53 is one of a few dominant genes for dwarfing in rice (Oryza sativa L.). In the present study, our genetic analysis confirmed that mutant characteristics including dwarfing, profuse tillering, thin stems and small panicles are all controlled by the dominant D-53 gene. We measured the length of each internode of KL908, a D-53-carrying line, and classified the dwarfism of KL908 into the dn-type. In addition, we measured elongation of the second sheath and α-amylase activity in the endosperm, and we characterized KL908 as a dwarf mutant that was neither gibberellic acid-deficient nor gibberellic acid-insensitive. Using a large F2 population obtained by crossing KL908 with a wild-type variety, NJ6, the D-53 gene was mapped to the terminal region of the short arm of chromosome 11, with one simple sequence repeat marker, Ds3, co-segregating, and the other, K81114, located 0.6 cM away.

  12. Flow diversion for complex intracranial aneurysms in young children.

    Science.gov (United States)

    Navarro, Ramon; Brown, Benjamin L; Beier, Alexandra; Ranalli, Nathan; Aldana, Philipp; Hanel, Ricardo A

    2015-03-01

    Pediatric intracranial aneurysms are exceedingly rare and account for less than 5% of all intracranial aneurysms. Open surgery to treat such aneurysms has been shown to be more durable than endovascular techniques, and durability of treatment is particularly important in the pediatric population. Over the past 2 decades, however, a marked shift in aneurysm treatment from open surgery toward endovascular procedures has occurred for adults. The authors describe their early experience in treating 3 unruptured pediatric brain aneurysms using the Pipeline embolization device (PED). The first patient, a girl with Majewski osteodysplastic primordial dwarfism Type II who was harboring multiple intracranial aneurysms, underwent two flow diversion procedures for a vertebrobasilar aneurysm and a supraclinoid internal carotid artery aneurysm. The second patient underwent PED placement on a previously coiled but enlarging posterior communicating artery aneurysm. All procedures were uneventful, with no postsurgical complications, and led to complete angiographic obliteration of the aneurysms. To the authors' knowledge, this is the first series of flow diversion procedures in children reported in the medical literature. While flow diversion is a new and relatively untested technology in children, outcomes in adults have been promising. For challenging lesions in the pediatric population, flow diversion may have a valuable role as a well-tolerated, safe treatment with durable results. Many issues remain to be addressed, such as the durability of flow diverters over a very long follow-up and vessel response to growth in the presence of an endoluminal device.

  13. Meier-Gorlin syndrome mutations disrupt an Orc1 CDK inhibitory domain and cause centrosome reduplication.

    Science.gov (United States)

    Hossain, Manzar; Stillman, Bruce

    2012-08-15

    Like DNA replication, centrosomes are licensed to duplicate once per cell division cycle to ensure genetic stability. In addition to regulating DNA replication, the Orc1 subunit of the human origin recognition complex controls centriole and centrosome copy number. Here we report that Orc1 harbors a PACT centrosome-targeting domain and a separate domain that differentially inhibits the protein kinase activities of Cyclin E-CDK2 and Cyclin A-CDK2. A cyclin-binding motif (Cy motif) is required for Orc1 to bind Cyclin A and inhibit Cyclin A-CDK2 kinase activity but has no effect on Cyclin E-CDK2 kinase activity. In contrast, Orc1 inhibition of Cyclin E-CDK2 kinase activity occurs by a different mechanism that is affected by Orc1 mutations identified in Meier-Gorlin syndrome patients. The cyclin/CDK2 kinase inhibitory domain of Orc1, when tethered to the PACT domain, localizes to centrosomes and blocks centrosome reduplication. Meier-Gorlin syndrome mutations that disrupt Cyclin E-CDK2 kinase inhibition also allow centrosome reduplication. Thus, Orc1 contains distinct domains that control centrosome copy number and DNA replication. We suggest that the Orc1 mutations present in some Meier-Gorlin syndrome patients contribute to the pronounced microcephaly and dwarfism observed in these individuals by altering centrosome duplication in addition to DNA replication defects.

  14. A Meier-Gorlin syndrome mutation in a conserved C-terminal helix of Orc6 impedes origin recognition complex formation.

    Science.gov (United States)

    Bleichert, Franziska; Balasov, Maxim; Chesnokov, Igor; Nogales, Eva; Botchan, Michael R; Berger, James M

    2013-10-08

    In eukaryotes, DNA replication requires the origin recognition complex (ORC), a six-subunit assembly that promotes replisome formation on chromosomal origins. Despite extant homology between certain subunits, the degree of structural and organizational overlap between budding yeast and metazoan ORC has been unclear. Using 3D electron microscopy, we determined the subunit organization of metazoan ORC, revealing that it adopts a global architecture very similar to the budding yeast complex. Bioinformatic analysis extends this conservation to Orc6, a subunit of somewhat enigmatic function. Unexpectedly, a mutation in the Orc6 C-terminus linked to Meier-Gorlin syndrome, a dwarfism disorder, impedes proper recruitment of Orc6 into ORC; biochemical studies reveal that this region of Orc6 associates with a previously uncharacterized domain of Orc3 and is required for ORC function and MCM2-7 loading in vivo. Together, our results suggest that Meier-Gorlin syndrome mutations in Orc6 impair the formation of ORC hexamers, interfering with appropriate ORC functions. DOI:http://dx.doi.org/10.7554/eLife.00882.001.

  15. Drosophila model of Meier-Gorlin syndrome based on the mutation in a conserved C-Terminal domain of Orc6.

    Science.gov (United States)

    Balasov, Maxim; Akhmetova, Katarina; Chesnokov, Igor

    2015-11-01

    Meier-Gorlin syndrome (MGS) is an autosomal recessive disorder characterized by microtia, primordial dwarfism, small ears, and skeletal abnormalities. Patients with MGS often carry mutations in the genes encoding the components of the pre-replicative complex such as Origin Recognition Complex (ORC) subunits Orc1, Orc4, Orc6, and helicase loaders Cdt1 and Cdc6. Orc6 is an important component of ORC and has functions in both DNA replication and cytokinesis. Mutation in conserved C-terminal motif of Orc6 associated with MGS impedes the interaction of Orc6 with core ORC. In order to study the effects of MGS mutation in an animal model system we introduced MGS mutation in Orc6 and established Drosophila model of MGS. Mutant flies die at third instar larval stage with abnormal chromosomes and DNA replication defects. The lethality can be rescued by elevated expression of mutant Orc6 protein. Rescued MGS flies are unable to fly and display multiple planar cell polarity defects. © 2015 Wiley Periodicals, Inc.

  16. Mutation Analysis of COL1A1 and COL1A2 in Fetuses with Osteogenesis Imperfecta Type II/III.

    Science.gov (United States)

    Wang, Wenbo; Wu, Qichang; Cao, Lin; Sun, Li; Xu, Yasong; Guo, Qiwei

    2015-01-27

    Aim: To analyze COL1A1/2 mutations in prenatal-onset OI for determine the proportion of mutations in type I collagen genes among prenatal onset OI and to provide additional data for genotype-phenotype analyses. Material and Methods: Ten cases of severe fetal short-limb dwarfism detected by antenatal ultrasonography were referred to our center. Before the termination of pregnancy, cordocentesis was performed for fetal karyotype and COL1A1/2 gene sequencing analysis. Postmortem radiographic examination was performed at all instances for definitive diagnosis. Results: COL1A1 and COL1A2 SNP and mutations were identified in all the cases. Among these, one synonymous SNP and four synonymous SNPs were recognized in COL1A1/2, respectively, seven cases have distinct heterozygous mutations and six new COL1A1/2 gene mutations were identified. Conclusion: There has been substantial progress in the identification of the molecular defects responsible for skeletal dysplasias. With the constant increase in the number of identified mutations in COL1A1 and COL1A2, genotype-phenotype correlation is becoming increasingly pertinent. © 2015 S. Karger AG, Basel.

  17. Whole-exome re-sequencing in a family quartet identifies POP1 mutations as the cause of a novel skeletal dysplasia.

    Directory of Open Access Journals (Sweden)

    Evgeny A Glazov

    2011-03-01

    Full Text Available Recent advances in DNA sequencing have enabled mapping of genes for monogenic traits in families with small pedigrees and even in unrelated cases. We report the identification of disease-causing mutations in a rare, severe, skeletal dysplasia, studying a family of two healthy unrelated parents and two affected children using whole-exome sequencing. The two affected daughters have clinical and radiographic features suggestive of anauxetic dysplasia (OMIM 607095, a rare form of dwarfism caused by mutations of RMRP. However, mutations of RMRP were excluded in this family by direct sequencing. Our studies identified two novel compound heterozygous loss-of-function mutations in POP1, which encodes a core component of the RNase mitochondrial RNA processing (RNase MRP complex that directly interacts with the RMRP RNA domains that are affected in anauxetic dysplasia. We demonstrate that these mutations impair the integrity and activity of this complex and that they impair cell proliferation, providing likely molecular and cellular mechanisms by which POP1 mutations cause this severe skeletal dysplasia.

  18. XIAO is involved in the control of organ size by contributing to the regulation of signaling and homeostasis of brassinosteroids and cell cycling in rice.

    Science.gov (United States)

    Jiang, Yunhe; Bao, Liang; Jeong, So-Yoon; Kim, Seong-Ki; Xu, Caiguo; Li, Xianghua; Zhang, Qifa

    2012-05-01

    Organ size is determined by cell number and size, and involves two fundamental processes: cell proliferation and cell expansion. Although several plant hormones are known to play critical roles in shaping organ size by regulating the cell cycle, it is not known whether brassinosteroids (BRs) are also involved in regulating cell division. Here we identified a rice T-DNA insertion mutant for organ size, referred to as xiao, that displays dwarfism and erect leaves, typical BR-related phenotypes, together with reduced seed setting. XIAO is predicted to encode an LRR kinase. The small stature of the xiao mutant resulted from reduced organ sizes due to decreased cell numbers resulting from reduced cell division rate, as supported by the observed co-expression of XIAO with a number of genes involved in cell cycling. The xiao mutant displayed a tissue-specific enhanced BR response and greatly reduced BR contents at the whole-plant level. These results indicated that XIAO is a regulator of BR signaling and cell division. Thus, XIAO may provide a possible connection between BRs and cell-cycle regulation in controlling organ growth.

  19. LINE-1 Mediated Insertion into Poc1a (Protein of Centriole 1 A Causes Growth Insufficiency and Male Infertility in Mice.

    Directory of Open Access Journals (Sweden)

    Krista A Geister

    2015-10-01

    Full Text Available Skeletal dysplasias are a common, genetically heterogeneous cause of short stature that can result from disruptions in many cellular processes. We report the identification of the lesion responsible for skeletal dysplasia and male infertility in the spontaneous, recessive mouse mutant chagun. We determined that Poc1a, encoding protein of the centriole 1a, is disrupted by the insertion of a processed Cenpw cDNA, which is flanked by target site duplications, suggestive of a LINE-1 retrotransposon-mediated event. Mutant fibroblasts have impaired cilia formation and multipolar spindles. Male infertility is caused by defective spermatogenesis early in meiosis and progressive germ cell loss. Spermatogonial stem cell transplantation studies revealed that Poc1a is essential for normal function of both Sertoli cells and germ cells. The proliferative zone of the growth plate is small and disorganized because chondrocytes fail to re-align after cell division and undergo increased apoptosis. Poc1a and several other genes associated with centrosome function can affect the skeleton and lead to skeletal dysplasias and primordial dwarfisms. This mouse mutant reveals how centrosome dysfunction contributes to defects in skeletal growth and male infertility.

  20. Suppression of Dwarf and irregular xylem Phenotypes Generates Low-Acetylated Biomass Lines in Arabidopsis.

    Science.gov (United States)

    Bensussan, Matthieu; Lefebvre, Valérie; Ducamp, Aloïse; Trouverie, Jacques; Gineau, Emilie; Fortabat, Marie-Noëlle; Guillebaux, Alexia; Baldy, Aurélie; Naquin, Delphine; Herbette, Stéphane; Lapierre, Catherine; Mouille, Gregory; Horlow, Christine; Durand-Tardif, Mylène

    2015-06-01

    eskimo1-5 (esk1-5) is a dwarf Arabidopsis (Arabidopsis thaliana) mutant that has a constitutive drought syndrome and collapsed xylem vessels, along with low acetylation levels in xylan and mannan. ESK1 has xylan O-acetyltransferase activity in vitro. We used a suppressor strategy on esk1-5 to screen for variants with wild-type growth and low acetylation levels, a favorable combination for ethanol production. We found a recessive mutation in the KAKTUS (KAK) gene that suppressed dwarfism and the collapsed xylem character, the cause of decreased hydraulic conductivity in the esk1-5 mutant. Backcrosses between esk1-5 and two independent knockout kak mutants confirmed suppression of the esk1-5 effect. kak single mutants showed larger stem diameters than the wild type. The KAK promoter fused with a reporter gene showed activity in the vascular cambium, phloem, and primary xylem in the stem and hypocotyl. However, suppression of the collapsed xylem phenotype in esk1 kak double mutants was not associated with the recovery of cell wall O-acetylation or any major cell wall modifications. Therefore, our results indicate that, in addition to its described activity as a repressor of endoreduplication, KAK may play a role in vascular development. Furthermore, orthologous esk1 kak double mutants may hold promise for ethanol production in crop plants. © 2015 American Society of Plant Biologists. All Rights Reserved.

  1. Basal encephalocele associated with morning glory syndrome: case report Encefalocele basal associada a síndrome "morning glory": relato de caso

    Directory of Open Access Journals (Sweden)

    Ivanete Minotto

    2007-12-01

    Full Text Available The basal encephaloceles refer to rare entities and they correspond to herniation of brain tissue through defects of skull along the cribiform plate or the sphenoid bone. A rare morning glory syndrome, with characteristic retinal defect has been reported in association with basal encephaloceles. Hypophysis hormonal deficiencies may occur. We accounted for a pituitary dwarfism with delayed diagnosed transsphenoidal encephalocele associated with morning glory syndrome, showing the alterations found in retinography, computed tomography and magnetic resonance imaging.As encefaloceles basais são entidades raras e correspondem a herniações do tecido cerebral através de um defeito do crânio, ao longo da lâmina crivosa etmoidal ou do osso esfenoidal. A rara síndrome morning glory, com alterações de fundo de olho características pode apresentar-se associada à encefalocele basal. Deficiências hormonais hipofisárias podem ocorrer. Relatamos caso de nanismo hipofisário com encefalocele transesfenoidal de diagnóstico tardio associada à síndrome de morning glory, mostrando as alterações na retinografia, tomografia computadorizada e ressonância magnética.

  2. Defining the Sequence Elements and Candidate Genes for the Coloboma Mutation.

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Robb

    Full Text Available The chicken coloboma mutation exhibits features similar to human congenital developmental malformations such as ocular coloboma, cleft-palate, dwarfism, and polydactyly. The coloboma-associated region and encoded genes were investigated using advanced genomic, genetic, and gene expression technologies. Initially, the mutation was linked to a 990 kb region encoding 11 genes; the application of the genetic and genomic tools led to a reduction of the linked region to 176 kb and the elimination of 7 genes. Furthermore, bioinformatics analyses of capture array-next generation sequence data identified genetic elements including SNPs, insertions, deletions, gaps, chromosomal rearrangements, and miRNA binding sites within the introgressed causative region relative to the reference genome sequence. Coloboma-specific variants within exons, UTRs, and splice sites were studied for their contribution to the mutant phenotype. Our compiled results suggest three genes for future studies. The three candidate genes, SLC30A5 (a zinc transporter, CENPH (a centromere protein, and CDK7 (a cyclin-dependent kinase, are differentially expressed (compared to normal embryos at stages and in tissues affected by the coloboma mutation. Of these genes, two (SLC30A5 and CENPH are considered high-priority candidate based upon studies in other vertebrate model systems.

  3. MOS11: a new component in the mRNA export pathway.

    Directory of Open Access Journals (Sweden)

    Hugo Germain

    2010-12-01

    Full Text Available Nucleocytoplasmic trafficking is emerging as an important aspect of plant immunity. The three related pathways affecting plant immunity include Nuclear Localization Signal (NLS-mediated nuclear protein import, Nuclear Export Signal (NES-dependent nuclear protein export, and mRNA export relying on MOS3, a nucleoporin belonging to the Nup107-160 complex. Here we report the characterization, identification, and detailed analysis of Arabidopsis modifier of snc1, 11 (mos11. Mutations in MOS11 can partially suppress the dwarfism and enhanced disease resistance phenotypes of snc1, which carries a gain-of-function mutation in a TIR-NB-LRR type Resistance gene. MOS11 encodes a conserved eukaryotic protein with homology to the human RNA binding protein CIP29. Further functional analysis shows that MOS11 localizes to the nucleus and that the mos11 mutants accumulate more poly(A mRNAs in the nucleus, likely resulting from reduced mRNA export activity. Epistasis analysis between mos3-1 and mos11-1 revealed that MOS11 probably functions in the same mRNA export pathway as MOS3, in a partially overlapping fashion, before the mRNA molecules pass through the nuclear pores. Taken together, MOS11 is identified as a new protein contributing to the transfer of mature mRNA from the nucleus to the cytosol.

  4. Palaeopathology of human remains of the 1st century BC–3rd century AD from Armenia (Beniamin, Shirakavan I

    Directory of Open Access Journals (Sweden)

    Khudaverdyan Anahit Yu.

    2015-06-01

    Full Text Available The aim of this article was to document the pathology of the individuals from the archeological sites of Beniamin and Shirakavan I, Armenia, dated on the 1st century BC - 3rd century AD. The findings revealed that two groups differed in mean age at death of adults. At Beniamin it was 24 years, 40.8 years for males and 30.9 years for females, whereas at Shirakavanit it was 29.3 years, 29.6 years for males and 35.8 years for females. The greatest mortality appeared to have occurred when the children reached the age of one year (Beniamin. The population had high number of young-adult females with a cause of death associated with child-bearing. Very few females survived to old age. Traumatic conditions (63.64% and enamel hypoplasias (57.2% have a high frequency in the skeletal material from Shirakavan. The volume of selection of Shirakavan does not allow itself to so big discussion as it was possible with the Beniamin site. Fewer hypoplasias in Beniamin group indicate that food resources were more abundant and more easily exploited. The small frequency of a periodontal disorder indicates that dental hygiene was good during the Antiquity period. We here report a case of possible pituitary dwarfism and a case of decapitation.

  5. Morphological and cytological responses of Ammonia (foraminifera) to copper contamination: Implication for the use of foraminifera as bioindicators of pollution

    Energy Technology Data Exchange (ETDEWEB)

    Le Cadre, Valerie [Universite d' Angers, UPRES-EA 2644, Laboratoire de Geologie, 2 Bd Lavoisier 49045 Angers cedex (France) and LEBIM - Laboratoire d' Etude des Bio-Indicateurs Marins, 85350 Ile d' Yeu (France)]. E-mail: val.jeje@wanadoo.fr; Debenay, Jean-Pierre [Universite d' Angers, UPRES-EA 2644, Laboratoire de Geologie, 2 Bd Lavoisier 49045 Angers cedex (France); LEBIM - Laboratoire d' Etude des Bio-Indicateurs Marins, 85350 Ile d' Yeu (France)

    2006-09-15

    The effect of graded concentrations of copper was analyzed at morphological and cytological levels on two species of Ammonia (foraminifera) often found in polluted areas. The two species were sensitive to low concentration, but survived high concentration (threshold value < 10 {mu}g l{sup -1}, lethal value > 200 {mu}g l{sup -1}), which gives them a high potential value as bioindicators. Increasing concentrations lead to (1) increasing delay before production of new chambers, explaining dwarfism in polluted areas; (2) increasing delay before reproduction and decreasing number of juveniles, explaining low density; and (3) increasing proportion of deformed tests. Cytological modifications occurred only in deformed specimens (thickening of the organic lining, proliferation of fibrillar and of large lipidic vesicles, increased number of residual bodies). They may be responsible for anomalies in biomineralization processes. The detection of sulfur in deformed specimens suggests that foraminifers may have a detoxification mechanism with production of a metallothionein-like protein. - Results suggest a detoxification mechanism for copper in foraminifera.

  6. Forward Genetics by Sequencing EMS Variation-Induced Inbred Lines

    Directory of Open Access Journals (Sweden)

    Charles Addo-Quaye

    2017-02-01

    Full Text Available In order to leverage novel sequencing techniques for cloning genes in eukaryotic organisms with complex genomes, the false positive rate of variant discovery must be controlled for by experimental design and informatics. We sequenced five lines from three pedigrees of ethyl methanesulfonate (EMS-mutagenized Sorghum bicolor, including a pedigree segregating a recessive dwarf mutant. Comparing the sequences of the lines, we were able to identify and eliminate error-prone positions. One genomic region contained EMS mutant alleles in dwarfs that were homozygous reference sequences in wild-type siblings and heterozygous in segregating families. This region contained a single nonsynonymous change that cosegregated with dwarfism in a validation population and caused a premature stop codon in the Sorghum ortholog encoding the gibberellic acid (GA biosynthetic enzyme ent-kaurene oxidase. Application of exogenous GA rescued the mutant phenotype. Our method for mapping did not require outcrossing and introduced no segregation variance. This enables work when line crossing is complicated by life history, permitting gene discovery outside of genetic models. This inverts the historical approach of first using recombination to define a locus and then sequencing genes. Our formally identical approach first sequences all the genes and then seeks cosegregation with the trait. Mutagenized lines lacking obvious phenotypic alterations are available for an extension of this approach: mapping with a known marker set in a line that is phenotypically identical to starting material for EMS mutant generation.

  7. Novel mutations in natriuretic peptide receptor-2 gene underlie acromesomelic dysplasia, type maroteaux

    Directory of Open Access Journals (Sweden)

    Khan Saadullah

    2012-06-01

    Full Text Available Abstract Background Natriuretic peptides (NPs are peptide hormones that exert their biological actions by binding to three types of cell surface natriuretic peptide receptors (NPRs. The receptor NPR-B binding C-type natriuretic peptide (CNP acts locally as a paracrine and/or autocrine regulator in a wide variety of tissues. Mutations in the gene NPR2 have been shown to cause acromesomelic dysplasia-type Maroteaux (AMDM, an autosomal recessive skeletal disproportionate dwarfism disorder in humans. Methods In the study, presented here, genotyping of six consanguineous families of Pakistani origin with AMDM was carried out using polymorphic microsatellite markers, which are closely linked to the gene NPR2 on chromosome 9p21-p12. To screen for mutations in the gene NPR2, all of its coding exons and splice junction sites were PCR amplified from genomic DNA of affected and unaffected individuals of the families and sequenced. Results Sequence analysis of the gene NPR2 identified a novel missence mutation (p.T907M in five families, and a splice donor site mutation c.2986 + 2 T > G in the other family. Conclusion We have described two novel mutations in the gene NPR2. The presence of the same mutation (p.T907M and haplotype in five families (A, B, C, D, E is suggestive of a founder effect.

  8. Whole-exome re-sequencing in a family quartet identifies POP1 mutations as the cause of a novel skeletal dysplasia.

    Directory of Open Access Journals (Sweden)

    Evgeny A Glazov

    2011-03-01

    Full Text Available Recent advances in DNA sequencing have enabled mapping of genes for monogenic traits in families with small pedigrees and even in unrelated cases. We report the identification of disease-causing mutations in a rare, severe, skeletal dysplasia, studying a family of two healthy unrelated parents and two affected children using whole-exome sequencing. The two affected daughters have clinical and radiographic features suggestive of anauxetic dysplasia (OMIM 607095, a rare form of dwarfism caused by mutations of RMRP. However, mutations of RMRP were excluded in this family by direct sequencing. Our studies identified two novel compound heterozygous loss-of-function mutations in POP1, which encodes a core component of the RNase mitochondrial RNA processing (RNase MRP complex that directly interacts with the RMRP RNA domains that are affected in anauxetic dysplasia. We demonstrate that these mutations impair the integrity and activity of this complex and that they impair cell proliferation, providing likely molecular and cellular mechanisms by which POP1 mutations cause this severe skeletal dysplasia.

  9. Expression of a partially deleted gene of human type II procollagen (COL2A1) in transgenic mice produces a chondrodysplasia

    Energy Technology Data Exchange (ETDEWEB)

    Vandenberg, P.; Khillan, J.S.; Prockop, D.J.; Helminen, H.; Kontusaari, S.; Ala-Kokko, L. (Thomas Jefferson Univ., Philadelphia, PA (United States))

    1991-09-01

    A minigene version of the human gene for type II procollagen (COL2AI) was prepared that lacked a large central region containing 12 of the 52 exons and therefore 291 of the 1523 codons of the gene. The construct was modeled after sporadic in-frame deletions of collagen genes that cause synthesis of shortened pro{alpha} chains that associate with normal pro{alpha} chains and thereby cause degradation of the shortened and normal pro{alpha} chains through a process called procollagen suicide. The gene construct was used to prepare five lines of transgenic mice expressing the minigene. A large proportion of the mice expressing the minigene developed a phenotype of a chondrodysplasia with dwarfism, short and thick limbs, a short snout, a cranial bulge, a cleft palate, and delayed mineralization of bone. A number of mice died shortly after birth. Microscopic examination of cartilage revealed decreased density and organization of collagen fibrils. In cultured chondrocytes from the transgenic mice, the minigene was expressed as shortened pro{alpha}1(II) chains that were disulfide-linked to normal mouse pro{alpha}1(II) chains. Therefore, the phenotype is probably explained by depletion of the endogenous mouse type II procollagen through the phenomenon of procollagen suicide.

  10. Mutations in ribosomal proteins, RPL4 and RACK1, suppress the phenotype of a thermospermine-deficient mutant of Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Jun-ichi Kakehi

    Full Text Available Thermospermine acts in negative regulation of xylem differentiation and its deficient mutant of Arabidopsis thaliana, acaulis5 (acl5, shows excessive xylem formation and severe dwarfism. Studies of two dominant suppressors of acl5, sac51-d and sac52-d, have revealed that SAC51 and SAC52 encode a transcription factor and a ribosomal protein L10 (RPL10, respectively, and these mutations enhance translation of the SAC51 mRNA, which contains conserved upstream open reading frames in the 5' leader. Here we report identification of SAC53 and SAC56 responsible for additional suppressors of acl5. sac53-d is a semi-dominant allele of the gene encoding a receptor for activated C kinase 1 (RACK1 homolog, a component of the 40S ribosomal subunit. sac56-d represents a semi-dominant allele of the gene for RPL4. We show that the GUS reporter activity driven by the CaMV 35S promoter plus the SAC51 5' leader is reduced in acl5 and restored by sac52-d, sac53-d, and sac56-d as well as thermospermine. Furthermore, the SAC51 mRNA, which may be a target of nonsense-mediated mRNA decay, was found to be stabilized in these ribosomal mutants and by thermospermine. These ribosomal proteins are suggested to act in the control of uORF-mediated translation repression of SAC51, which is derepressed by thermospermine.

  11. Manipulation of Guaiacyl and Syringyl Monomer Biosynthesis in an Arabidopsis Cinnamyl Alcohol Dehydrogenase Mutant Results in Atypical Lignin Biosynthesis and Modified Cell Wall Structure

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Nickolas A.; Tobimatsu, Yuki; Ciesielski, Peter N.; Ximenes, Eduardo; Ralph, John; Donohoe, Bryon S.; Ladisch, Michael; Chapple, Clint

    2015-08-01

    Modifying lignin composition and structure is a key strategy to increase plant cell wall digestibility for biofuel production. Disruption of the genes encoding both cinnamyl alcohol dehydrogenases (CADs), including CADC and CADD, in Arabidopsis thaliana results in the atypical incorporation of hydroxycinnamaldehydes into lignin. Another strategy to change lignin composition is downregulation or overexpression of ferulate 5-hydroxylase (F5H), which results in lignins enriched in guaiacyl or syringyl units, respectively. Here, we combined these approaches to generate plants enriched in coniferaldehyde-derived lignin units or lignins derived primarily from sinapaldehyde. The cadc cadd and ferulic acid hydroxylase1 (fah1) cadc cadd plants are similar in growth to wild-type plants even though their lignin compositions are drastically altered. In contrast, disruption of CAD in the F5H-overexpressing background results in dwarfism. The dwarfed phenotype observed in these plants does not appear to be related to collapsed xylem, a hallmark of many other lignin-deficient dwarf mutants. cadc cadd, fah1 cadc cadd, and cadd F5H-overexpressing plants have increased enzyme-catalyzed cell wall digestibility. Given that these CAD-deficient plants have similar total lignin contents and only differ in the amounts of hydroxycinnamaldehyde monomer incorporation, these results suggest that hydroxycinnamaldehyde content is a more important determinant of digestibility than lignin content.

  12. Not all hypochondroplasia families are linked to chromosome 4p16.3

    Energy Technology Data Exchange (ETDEWEB)

    Rousseau, F.; Munnich, A.; Merrer, M.Le. [INSERM, Paris (France)] [and others

    1994-09-01

    Achondroplasia (ACH, MIM 100800) and hypochondroplasia (HCH, MIM 146000) are short limb dwarfism with enlarged head sharing some specific radiological features. Inter- and intrafamilial clinical variability and histolopathological aspects of the growth cartilage suggested that ACH and HCH are allelic disorders. Recently, the gene for achondroplasia was mapped to chromosome 4p and no recombinants were found in 9 families with hypochondroplasia between D4S111 and the telomere (Zmax=1.70, {theta}=0). By using an additional polymorphic DNA marker which detects VNTR-like polymorphism at the D4S227 locus and a new microsatellite at locus D4S? (AFM163yc1), we observed recombinant events with markers of the chromosome 4p16.3 in 3/10 hypochondroplasia families, indicating that not all hypochondroplasia families are linked to chromosome 4p. A fibroblast growth factor receptor (FGFR3) expressed in chondrocytes during endochondral ossification which is located in the 2.5 Mb candidate region for achondroplasia was regarded as a good candidate gene. No major rearrangement of the FGFR3 gene was detected by Southern blot analysis using an FGFR3 cDNA probe. Further investigations will be required to conclude as to the possible involvement of this gene in ACH.

  13. Correction of murine mucopolysaccharidosis VII by a human. beta. -glucuronidase transgene

    Energy Technology Data Exchange (ETDEWEB)

    Kyle, J.W.; Vogler, C.; Hoffmann, J.W.; Sly, W.S. (St. Louis Univ. School of Medicine, MO (USA)); Birkenmeier, E.H.; Gwynn, B. (Jackson Laboratory, Bar Harbor, ME (USA))

    1990-05-01

    The authors recently described a murine model for mucopolysaccharidosis VII in mice that have an inherited deficiency of {beta}-glucuronidase. Affected mice, of genotype gus{sup mps}/gus{sup mps}, present clinical manifestations similar to those of humans with mucopolysaccharidosis VII (Sly syndrome) and are shown here to have secondary elevations of other lysosomal enzymes. The mucopolysaccharidosis VII phenotype in both species includes dwarfism, skeletal deformities, and premature death. Lysosome storage is visualized within enlarged vesicles and correlates biochemically with accumulation of undegraded and partially degraded glycosaminoglycans. In this report they describe the consequences of introducing the human {beta}-glucuronidase gene, GUSB, into gus{sup mps}/gus{sup mps} mice that produce virtually no murine {beta}-glucuronidase. Transgenic mice homozygous for the mucopolysaccharidosis VII mutation expressed high levels of human {beta}-glucuronidase activity in all tissues examined and were phenotypically normal. Biochemically, both the intralysosomal storage of glycosaminoglycans and the secondary elevation of other acid hydrolases were corrected. These findings demonstrate that the GUSB transgene is expressed in gus{sup mps}/gus{sup mps} mice and that human {beta}-glucuronidase corrects the murine mucopolysaccharidosis storage disease.

  14. Recessive omodysplasia: five new cases and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Elcioglu, Nursel H. [Department of Pediatric Genetics, Marmara University Hospital, Tophanelioglu cad 15, Altunizade, 34660 Istanbul (Turkey); Gustavson, Karl H. [Department of Clinical Genetics, Uppsala University Children' s Hospital, Uppsala (Sweden); Wilkie, Andrew O.M. [Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford (United Kingdom); Yueksel-Apak, Memune [Institute of Child Health, University of Istanbul, Istanbul (Turkey); Spranger, Juergen W. [Universitaets-Kinderklinik Mainz, Mainz (Germany); Greenwood Genetic Center, Greenwood, South Carolina (United States)

    2004-01-01

    Autosomal recessive omodysplasia (MIM 258315) is a rare skeletal dysplasia characterized by severe congenital micromelia with shortening and distal tapering of the humeri and femora to give a club-like appearance. Fewer than 20 cases have been reported in the literature so far. The purpose of this study was to more clearly describe the clinical and radiographic phenotypes and their changes with age. Five new patients, including two sibs, with autosomal recessive omodysplasia are presented. Clinical features are rhizomelic dwarfism with limited extension of elbows and knees and a distinct face with a short nose, depressed nasal bridge, long philtrum, midline haemangiomas in infants and cryptorchidism in males. Radiological findings are distal hypoplasia of the short humerus and femur with characteristic radial dislocation and radioulnar diastasis. Based on a review of these and 16 previously reported patients, the regressive nature of the humerofemoral changes and the obvious male predominance are stressed. Phenotypic similarities with the atelosteogenesis group of disorders and with diastrophic dysplasia suggest common pathogenetic mechanisms. (orig.)

  15. Glycosylation of inositol phosphorylceramide sphingolipids is required for normal growth and reproduction in Arabidopsis

    Energy Technology Data Exchange (ETDEWEB)

    Tartaglio, Virginia [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Rennie, Emilie A. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Univ. of Nebraska, Lincoln, NE (United States). Center for Plant Science Innovation and Dept. of Biochemistry; Cahoon, Rebecca [Univ. of Nebraska, Lincoln, NE (United States). Center for Plant Science Innovation and Dept. of Biochemistry; Wang, George [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Baidoo, Edward [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Mortimer, Jennifer C. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Cahoon, Edgar B. [Univ. of Nebraska, Lincoln, NE (United States). Center for Plant Science Innovation and Dept. of Biochemistry; Scheller, Henrik V. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Univ. of California, Berkeley, CA (United States). Dept. of Plant and Microbial Biology

    2016-09-19

    Sphingolipids are a major component of plant plasma membranes and endomembranes, and mediate a diverse range of biological processes. Study of the highly glycosylated glycosyl inositol phosphorylceramide (GIPC) sphingolipids has been slow as a result of challenges associated with the extractability of GIPCs, and their functions in the plant remain poorly characterized. We recently discovered an Arabidopsis GIPC glucuronosyltransferase, INOSITOL PHOSPHORYLCERAMIDE GLUCURONOSYLTRANSFERASE 1 (IPUT1), which is the first enzyme in the GIPC glycosylation pathway. Plants homozygous for the iput1 loss-of-function mutation were unobtainable, and so the developmental effects of reduced GIPC glucuronosylation could not be analyzed in planta. Using a pollen-specific rescue construct, we have here isolated homozygous iput1 mutants. The iput1 mutants show severe dwarfism, compromised pollen tube guidance, and constitutive activation of salicyclic acid-mediated defense pathways. The mutants also possess reduced GIPCs, increased ceramides, and an increased incorporation of short-chain fatty acids and dihydroxylated bases into inositol phosphorylceramides and GIPCs. The assignment of a direct role for GIPC glycan head groups in the impaired processes in iput1 mutants is complicated by the vast compensatory changes in the sphingolipidome; however, our results reveal that the glycosylation steps of GIPC biosynthesis are important regulated components of sphingolipid metabolism. In conclusion, this study corroborates previously suggested roles for GIPC glycans in plant growth and defense, suggests important role s for them in reproduction and demonstrates that the entire sphingolipidome is sensitive to their status.

  16. Precise localization of multiple epiphyseal dysplasia and pseudoachondroplasia mutations by genetic and physical mapping of chromosome 19

    Energy Technology Data Exchange (ETDEWEB)

    Knowlton, R.G.; Cekleniak, J.A. [Jefferson Medical College, Philadelphia, PA (United States); Cohn, D.H. [Cedars-Sinai Medical Center, Los Angeles, CA (United States)] [and others

    1994-09-01

    Multiple epiphyseal dysplasia (EDM1), a dominantly inherited chondrodysplasia resulting in peripheral joint deformities and premature osteoarthritis, and pseudoachondroplasia (PSACH), a more severe disorder associated with short-limbed dwarfism, have recently been mapped to the pericentromeric region of chromosome 19. Chondrocytes from some PSACH patients accumulate lamellar deposits in the endoplasmic reticulum that are immunologically cross-reactive with aggrecan. However, neither aggrecan nor any known candidate gene maps to the EDM1/PSACH region of chromosome 19. Genetic linkage mapping in two lage families had placed the disease locus between D19S215 (19p12) and D19S212 (19p13.1), an interval of about 3.5 Mb. With at least five potentially informative cross-overs within this interval, recombination mapping at greater resolution was undertaken. From cosmids assigned to the region by fluorescence in situ hybridization and contig assembly, dinucleotide repeat tracts were identified for use as polymorphic genetic markers. Linkage data from three new dinucleotide repeat markers from cosmids mapped between D19S212 and D19S215 limit the EDM1/PSACH locus to an interval spanning approximately 2 Mb.

  17. Genetic analysis and fine-mapping of a dwarfing with withered leaf-tip mutant in rice

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A dwarf mutant of rice(Oryza.sativa L.)by mutagenesis of ethylene methylsulfonate(EMS)treatment from Nipponbare was identified.The mutant exhibited phenotypes of dwarfism and withered leaf tip(dwll).Based on the internode length of dwl1,this mutant be longs to the dm type of dwarfing.Analysis of elongation of the second sheath and α-amylase activity in endosperm showed that the phenotype caused by dwll was insensitive to gibberellin acid treatment.Using a large F2 population derived from a cross between the dwll and an indica rice variety,TN1,the DWLl gene was mapped to the terminal region of the long arm of chromosome 3.Fine-mapping de-limited it into a 46 kb physical distance between two STS markers,HL921 and HL944,where 6 open reading frames were predicted.Cloning of DWL1 will contribute to dissecting molecular mechanism that regulates plant height in rice,which will be beneficial to molecular assisted selection of this important trait.

  18. Mucopolysaccharidoses and anaesthetic risks.

    Science.gov (United States)

    Sjøgren, P; Pedersen, T; Steinmetz, H

    1987-04-01

    The purpose of this review is to asses the current knowledge of mucopolysaccharidosis (MPS), with reference to the serious complications which may arise in connection with anaesthesia and operation. MPS consists of a heterogeneous group of hereditary diseases which are characterized by an abnormal accumulation of mucopolysaccharides, especially in cartilaginous and bone tissue. Because of their progressive and disabling nature, frequent surgical intervention is common, and is associated with a high degree of per- and postoperative risk. The clinical manifestations of MPS are frequently dwarfism, scaphocephaly, grotesque facial features with snub nose, hypertelorism, macroglossia and dental anomalies. The chest is deformed by pectus carinatum or excavatum, club-formed ribs and kyphosis with gibbus. Furthermore, cardiomegaly, abdomen pendens, hepatosplenomegaly, umbilical hernia, corneal clouding, conductive deafness and subnormal intelligence are common findings. Prior to operation, patients should be thoroughly evaluated through clinical examination and laboratory investigations. In particular, lung function should be optimized by lung physiotherapy and treatment of airway infections. When inducing general anaesthesia, spontaneous respiration is recommended until the patient has been intubated, as airway anomalies, bleeding and salivation may make intubation extremely difficult. Local or regional anaesthesia is often preferable, though age and mental status are relative contraindications. When used in combination with careful sedation, many problems may be overcome. Postoperatively, it is important to treat stagnation of secretions and airway infections with lung physiotherapy positive end-expiratory pressure, and antibiotics. In connection with anesthesia, it is vital to monitor the patient carefully before, during and after anaesthesia.

  19. Ror2 signaling is required for local upregulation of GDF6 and activation of BMP signaling at the neural plate border.

    Science.gov (United States)

    Schille, Carolin; Bayerlová, Michaela; Bleckmann, Annalen; Schambony, Alexandra

    2016-09-01

    The receptor tyrosine kinase Ror2 is a major Wnt receptor that activates β-catenin-independent signaling and plays a conserved role in the regulation of convergent extension movements and planar cell polarity in vertebrates. Mutations in the ROR2 gene cause recessive Robinow syndrome in humans, a short-limbed dwarfism associated with craniofacial malformations. Here, we show that Ror2 is required for local upregulation of gdf6 at the neural plate border in Xenopus embryos. Ror2 morphant embryos fail to upregulate neural plate border genes and show defects in the induction of neural crest cell fate. These embryos lack the spatially restricted activation of BMP signaling at the neural plate border at early neurula stages, which is required for neural crest induction. Ror2-dependent planar cell polarity signaling is required in the dorsolateral marginal zone during gastrulation indirectly to upregulate the BMP ligand Gdf6 at the neural plate border and Gdf6 is sufficient to rescue neural plate border specification in Ror2 morphant embryos. Thereby, Ror2 links Wnt/planar cell polarity signaling to BMP signaling in neural plate border specification and neural crest induction.

  20. Ellis-van Creveld syndrome in a fetus with rhizomelia and polydactyly. Report of a case diagnosed by genetic analysis, and correlation with pathological andradiologic findings.

    Science.gov (United States)

    Peraita-Ezcurra, Milena; Martínez-García, Mónica; Ruiz-Pérez, Víctor L; Sánchez-Gutiérrez, María Eugenia; Fenollar-Cortés, María; Vélez-Monsalve, Camilo; Ramos-Corrales, Carmen; Pastor, Ignacio; Santonja, Carlos; Trujillo-Tiebas, María José

    2012-05-10

    Ellis-van Creveld syndrome is an autosomal recessive disorder mainly characterized by a disproportionate limb dwarfism, chondroectodermal dysplasia, congenital heart disease, postaxial polydactyly, and dysplastic fingernails and teeth. Only 300 cases have been published worldwide. We report a 21-week fetus with rhizomelia and polydactyly detected. Gross photographs, radiologic studies and pathological study were performed leading to the clinico-pathological suspicion of EvC. DNA from fresh fetal tissue was extracted for sequencing the EVC and EVC2 genes. p.W215X and p.R677X mutations were identified in the EVC2 gene in the fetal sample. Parental sample analysis showed the p.W215X mutation to be inherited from the mother and the p.R677X mutation from the father. The clinical information is essential not only to arrive at a correct diagnosis in fetuses with pathologic ultrasound findings, but also to offer a proper genetic counseling to the parents and their relatives.

  1. Early Holocene turnover, followed by stability, in a Caribbean lizard assemblage

    Science.gov (United States)

    Kemp, Melissa E.; Hadly, Elizabeth A.

    2016-03-01

    Understanding how communities are impacted by environmental perturbations is integral for addressing the ongoing biodiversity crisis that impacts ecosystems worldwide. The fossil record serves as a window into ancient interactions and the responses of communities to past perturbations. Here, we re-examine paleontological data from Katouche Bay, Anguilla, a Holocene site in the Lesser Antilles. We reveal that the site was more diverse than previously indicated, with long-term, continuous records of three genera of extant lizards (Anolis, Ameiva, and Thecadactylus), and the early Holocene presence of Leiocephalus, a large ground-dwelling lizard that has since been completely extirpated from the Lesser Antilles. The disappearance of Leiocephalus from Katouche Bay resulted in high turnover, decreased evenness, and decreased species richness-a trend that continues to the present day. Our body size reconstructions for the most abundant genus, Anolis, are consistent with the presence of only one species, Anolis cf. gingivinus, at Katouche Bay throughout the Holocene, contrary to previously published studies. Additionally, we find no evidence of dwarfism in A. cf. gingivinus, which contrasts with a global study of contemporary insular lizards. Our data reveal that the impacts of diversity loss on lizard communities are long lasting and irreversible over millennia.

  2. Phosphatidylserine synthase 1 is required for inflorescence meristem and organ development in Arabidopsis.

    Science.gov (United States)

    Liu, Chengwu; Yin, Hengfu; Gao, Peng; Hu, Xiaohe; Yang, Jun; Liu, Zhongchi; Fu, Xiangdong; Luo, Da

    2013-08-01

    Phosphatidylserine (PS), a quantitatively minor membrane phospholipid, is involved in many biological processes besides its role in membrane structure. One PS synthesis gene, PHOSPHATIDYLSERINE SYNTHASE1 (PSS1), has been discovered to be required for microspore development in Arabidopsis thaliana L. but how PSS1 affects postembryonic development is still largely unknown. Here, we show that PSS1 is also required for inflorescence meristem and organ development in Arabidopsis. Disruption of PSS1 causes severe dwarfism, smaller lateral organs and reduced size of inflorescence meristem. Morphological and molecular studies suggest that both cell division and cell elongation are affected in the pss1-1 mutant. RNA in situ hybridization and promoter GUS analysis show that expression of both WUSCHEL (WUS) and CLAVATA3 (CLV3) depend on PSS1. Moreover, the defect in meristem maintenance is recovered and the expression of WUS and CLV3 are restored in the pss1-1 clv1-1 double mutant. Both SHOOTSTEMLESS (STM) and BREVIPEDICELLUS (BP) are upregulated, and auxin distribution is disrupted in rosette leaves of pss1-1. However, expression of BP, which is also a regulator of internode development, is lost in the pss1-1 inflorescence stem. Our data suggest that PSS1 plays essential roles in inflorescence meristem maintenance through the WUS-CLV pathway, and in leaf and internode development by differentially regulating the class I KNOX genes. © 2013 Institute of Botany, Chinese Academy of Sciences.

  3. Canine fibroblast growth factor receptor 3 sequence is conserved across dogs of divergent skeletal size

    Directory of Open Access Journals (Sweden)

    Grossman Deborah I

    2008-10-01

    Full Text Available Abstract Background Fibroblast growth factor receptor 3 (FGFR3 is expressed in the growth plate of endochondral bones and serves as a negative regulator of linear bone elongation. Activating mutations severely limit bone growth, resulting in dwarfism, while inactivating mutations significantly enhance bone elongation and overall skeletal size. Domesticated dogs exhibit the greatest skeletal size diversity of any species and, given the regulatory role of FGFR3 on growth plate proliferation, we asked whether sequence differences in FGFR3 could account for some of the size differences. Methods All exons, the promoter region, and 60 bp of the 3' flanking region of the canine FGFR3 gene were sequenced for nine different dog breeds representing a spectrum of skeletal size. The resultant sequences were compared to the reference Boxer genome sequence. Results There was no variation in sequence for any FGFR3 exons, promoter region, or 3' flanking sequence across all breeds evaluated. Conclusion The results suggest that, regardless of domestication selection pressure to develop breeds having extreme differences in skeletal size, the FGFR3 gene is conserved. This implies a critical role for this gene in normal skeletal integrity and indicates that other genes account for size variability in dogs.

  4. The maximum rate of mammal evolution.

    Science.gov (United States)

    Evans, Alistair R; Jones, David; Boyer, Alison G; Brown, James H; Costa, Daniel P; Ernest, S K Morgan; Fitzgerald, Erich M G; Fortelius, Mikael; Gittleman, John L; Hamilton, Marcus J; Harding, Larisa E; Lintulaakso, Kari; Lyons, S Kathleen; Okie, Jordan G; Saarinen, Juha J; Sibly, Richard M; Smith, Felisa A; Stephens, Patrick R; Theodor, Jessica M; Uhen, Mark D

    2012-03-13

    How fast can a mammal evolve from the size of a mouse to the size of an elephant? Achieving such a large transformation calls for major biological reorganization. Thus, the speed at which this occurs has important implications for extensive faunal changes, including adaptive radiations and recovery from mass extinctions. To quantify the pace of large-scale evolution we developed a metric, clade maximum rate, which represents the maximum evolutionary rate of a trait within a clade. We applied this metric to body mass evolution in mammals over the last 70 million years, during which multiple large evolutionary transitions occurred in oceans and on continents and islands. Our computations suggest that it took a minimum of 1.6, 5.1, and 10 million generations for terrestrial mammal mass to increase 100-, and 1,000-, and 5,000-fold, respectively. Values for whales were down to half the length (i.e., 1.1, 3, and 5 million generations), perhaps due to the reduced mechanical constraints of living in an aquatic environment. When differences in generation time are considered, we find an exponential increase in maximum mammal body mass during the 35 million years following the Cretaceous-Paleogene (K-Pg) extinction event. Our results also indicate a basic asymmetry in macroevolution: very large decreases (such as extreme insular dwarfism) can happen at more than 10 times the rate of increases. Our findings allow more rigorous comparisons of microevolutionary and macroevolutionary patterns and processes.

  5. Achondroplasia among ancient populations of mesoamerica and South America: Iconographic and Archaeological Evidence.

    Science.gov (United States)

    Rodríguez, Carlos A; Isaza, Carolina; Pachajoa, Harry

    2012-07-01

    Achondroplasia is the most frequent form of short-limb dwarfism. Affected individuals exhibit short stature caused by rhizomelic shortening of the limbs, characteristic facies with frontal bossing and mid-face hypoplasia, genu varum, and trident hand. Although the etiology of this disease was reported in 1994, evidence of this disease in ancient populations has been found in populations of ancient Egypt (2500 BC) and it has been documented in ancient American populations. To analyze the presence of individuals with achondroplasia in the Mayan state society of Mexico and Guatemala, during the Classical (100- 950 AC ) and Post-Classical (950 - 1519 AC ) periods; likewise, in the hierarchical-chieftain society of Tumaco-la Tolita (300 BC - 600 AC ) from the Colombia-Ecuador Pacific coast, and the Moche state society (100 - 600 AC ) from the northern coast of Peru. Iconographic and clinical-morphological studies of some of the most important artistic representations of individuals of short stature in these three cultures. We present the hypothesis that the individuals with short stature were somehow associated with the political and religious power elite.

  6. Unique Dental Morphology of Homo floresiensis and Its Evolutionary Implications.

    Science.gov (United States)

    Kaifu, Yousuke; Kono, Reiko T; Sutikna, Thomas; Saptomo, Emanuel Wahyu; Jatmiko; Due Awe, Rokus

    2015-01-01

    Homo floresiensis is an extinct, diminutive hominin species discovered in the Late Pleistocene deposits of Liang Bua cave, Flores, eastern Indonesia. The nature and evolutionary origins of H. floresiensis' unique physical characters have been intensively debated. Based on extensive comparisons using linear metric analyses, crown contour analyses, and other trait-by-trait morphological comparisons, we report here that the dental remains from multiple individuals indicate that H. floresiensis had primitive canine-premolar and advanced molar morphologies, a combination of dental traits unknown in any other hominin species. The primitive aspects are comparable to H. erectus from the Early Pleistocene, whereas some of the molar morphologies are more progressive even compared to those of modern humans. This evidence contradicts the earlier claim of an entirely modern human-like dental morphology of H. floresiensis, while at the same time does not support the hypothesis that H. floresiensis originated from a much older H. habilis or Australopithecus-like small-brained hominin species currently unknown in the Asian fossil record. These results are however consistent with the alternative hypothesis that H. floresiensis derived from an earlier Asian Homo erectus population and experienced substantial body and brain size dwarfism in an isolated insular setting. The dentition of H. floresiensis is not a simple, scaled-down version of earlier hominins.

  7. Unique Dental Morphology of Homo floresiensis and Its Evolutionary Implications.

    Directory of Open Access Journals (Sweden)

    Yousuke Kaifu

    Full Text Available Homo floresiensis is an extinct, diminutive hominin species discovered in the Late Pleistocene deposits of Liang Bua cave, Flores, eastern Indonesia. The nature and evolutionary origins of H. floresiensis' unique physical characters have been intensively debated. Based on extensive comparisons using linear metric analyses, crown contour analyses, and other trait-by-trait morphological comparisons, we report here that the dental remains from multiple individuals indicate that H. floresiensis had primitive canine-premolar and advanced molar morphologies, a combination of dental traits unknown in any other hominin species. The primitive aspects are comparable to H. erectus from the Early Pleistocene, whereas some of the molar morphologies are more progressive even compared to those of modern humans. This evidence contradicts the earlier claim of an entirely modern human-like dental morphology of H. floresiensis, while at the same time does not support the hypothesis that H. floresiensis originated from a much older H. habilis or Australopithecus-like small-brained hominin species currently unknown in the Asian fossil record. These results are however consistent with the alternative hypothesis that H. floresiensis derived from an earlier Asian Homo erectus population and experienced substantial body and brain size dwarfism in an isolated insular setting. The dentition of H. floresiensis is not a simple, scaled-down version of earlier hominins.

  8. New Heteroceratidae (Ammonoidea) from the late Barremian deepening succession of Marseille (Bouches-du-Rhône, France)

    Science.gov (United States)

    Frau, Camille; Delanoy, Gérard; Masse, Jean-Pierre; Lanteaume, Cyprien; Tendil, Anthony J. B.

    2016-06-01

    Investigation of the late Barremian deepening succession of the Provence platform, cropping out south of Marseille (Bouches-du-Rhône, France), has yielded a new ammonite fauna belonging to the Martelites sarasini Subzone (Martelites sarasini Zone). The fauna is dominated by representatives of the Heteroceratidae Spath, characterized by different patterns of coiling, high intraspecific variabilities and dwarfism. These heteroceratids are distinctive and utterly different from all previously known taxa, and this justifies the introduction of the new taxa Heteroceras denizoti sp. nov., Heteroceras veratiae sp. nov., Calanquites gen. nov., based on Imerites katsharavai Rouchadzé; Giovaraites gen. nov., based on Giovaraites massiliae gen. et sp. nov., Barguesiella gen. nov., based on Barguesiella goudesense gen. et sp. nov. and the closely allied Barguesiella mantei gen. et sp. nov. The occurrence of the latter species at the top of the Maiolica Formation in Italy questions its early Aptian age assumed in the literature. The newly described fauna could be considered as the first case of micromorphy in the Heteroceratidae. Its biostratigraphy, palaeoenvironmental and palaeobiogeographical significance are discussed.

  9. Loss of ATRX does not confer susceptibility to osteoarthritis.

    Directory of Open Access Journals (Sweden)

    Lauren A Solomon

    Full Text Available The chromatin remodelling protein ATRX is associated with the rare genetic disorder ATR-X syndrome. This syndrome includes developmental delay, cognitive impairment, and a variety of skeletal deformities. ATRX plays a role in several basic chromatin-mediated cellular events including DNA replication, telomere stability, gene transcription, and chromosome congression and cohesion during cell division. We have used a loss-of-function approach to directly investigate the role of Atrx in the adult skeleton in three different models of selective Atrx loss. We specifically targeted deletion of Atrx to the forelimb mesenchyme, to cartilage and to bone-forming osteoblasts. We previously demonstrated that loss of ATRX in forelimb mesenchyme causes brachydactyly while deletion in chondrocytes had minimal effects during development. We now show that targeted deletion of Atrx in osteoblasts causes minor dwarfism but does not recapitulate most of the skeletal phenotypes seen in ATR-X syndrome patients. In adult mice from all three models, we find that joints lacking Atrx are not more susceptible to osteoarthritis, as determined by OARSI scoring and immunohistochemistry. These results indicate that while ATRX plays limited roles during early stages of skeletal development, deficiency of the protein in adult tissues does not confer susceptibility to osteoarthritis.

  10. Loss of ATRX does not confer susceptibility to osteoarthritis.

    Science.gov (United States)

    Solomon, Lauren A; Russell, Bailey A; Makar, David; Bérubé, Nathalie G; Beier, Frank

    2013-01-01

    The chromatin remodelling protein ATRX is associated with the rare genetic disorder ATR-X syndrome. This syndrome includes developmental delay, cognitive impairment, and a variety of skeletal deformities. ATRX plays a role in several basic chromatin-mediated cellular events including DNA replication, telomere stability, gene transcription, and chromosome congression and cohesion during cell division. We have used a loss-of-function approach to directly investigate the role of Atrx in the adult skeleton in three different models of selective Atrx loss. We specifically targeted deletion of Atrx to the forelimb mesenchyme, to cartilage and to bone-forming osteoblasts. We previously demonstrated that loss of ATRX in forelimb mesenchyme causes brachydactyly while deletion in chondrocytes had minimal effects during development. We now show that targeted deletion of Atrx in osteoblasts causes minor dwarfism but does not recapitulate most of the skeletal phenotypes seen in ATR-X syndrome patients. In adult mice from all three models, we find that joints lacking Atrx are not more susceptible to osteoarthritis, as determined by OARSI scoring and immunohistochemistry. These results indicate that while ATRX plays limited roles during early stages of skeletal development, deficiency of the protein in adult tissues does not confer susceptibility to osteoarthritis.

  11. Loss of ATRX in chondrocytes has minimal effects on skeletal development.

    Directory of Open Access Journals (Sweden)

    Lauren A Solomon

    Full Text Available BACKGROUND: Mutations in the human ATRX gene cause developmental defects, including skeletal deformities and dwarfism. ATRX encodes a chromatin remodeling protein, however the role of ATRX in skeletal development is currently unknown. METHODOLOGY/PRINCIPAL FINDINGS: We induced Atrx deletion in mouse cartilage using the Cre-loxP system, with Cre expression driven by the collagen II (Col2a1 promoter. Growth rate, body size and weight, and long bone length did not differ in Atrx(Col2cre mice compared to control littermates. Histological analyses of the growth plate did not reveal any differences between control and mutant mice. Expression patterns of Sox9, a transcription factor required for cartilage morphogenesis, and p57, a marker of cell cycle arrest and hypertrophic chondrocyte differentiation, was unaffected. However, loss of ATRX in cartilage led to a delay in the ossification of the hips in some mice. We also observed hindlimb polydactily in one out of 61 mutants. CONCLUSIONS/SIGNIFICANCE: These findings indicate that ATRX is not directly required for development or growth of cartilage in the mouse, suggesting that the short stature in ATR-X patients is caused by defects in cartilage-extrinsic mechanisms.

  12. Complex oncologic reconstruction of a mandibular and floor of mouth defect with a fibula free flap in an achondroplastic patient.

    Science.gov (United States)

    García-Rozado, Alvaro; Martín Sastre, Roberto J; López Cedrún, José L

    2003-01-01

    The fibular free flap is seen as one of the foremost technical options in mandibular reconstruction, especially in those defects where long bone is required. Cases with squamous-cell carcinoma of the floor of the mouth with mandibular spread and subsequent segmentary mandibular removal are the cornerstone examples. A case of squamous-cell carcinoma of the whole floor of the mouth with mandibular invasion is reported. Radical resection of the floor of the mouth and bilateral mandibular horizontal ramus was performed, with a bony defect extending from angle to angle. The patient revealed an achondroplastic condition, with remarkable dwarfism and long-bone morphological alterations, that minimized the potential fibular length to transfer. A microsurgical reconstruction with an osteocutaneous fibular free flap was undertaken. The flap design was technically compromised by the forward bowing of the fibula and the ossification of the interosseous membrane. Specific intraoperative strategies for dealing with anatomic variations are discussed. The fibular free flap is an excellent technique for mandibular reconstruction. Morphological deviations can modify the design of the flap. Achondroplasia is not a deterrent in successful use of the free fibula flap for reconstruction of the head and neck in adequately selected cases.

  13. Zinc: the neglected nutrient.

    Science.gov (United States)

    Shambaugh, G E

    1989-03-01

    Zinc was first recognized as essential for animals at the University of Illinois School of Agriculture in 1916, when it was found that zinc-deficient baby pigs were runty, developed dermatitis on their legs, and were sterile. Zinc deficiency was first recognized in man by Dr. Ananda Prasad of Detroit 26 years ago when he measured serum and hair zinc levels in young male Egyptian dwarfs who had failed to mature and were small in stature. By simply adding zinc to their regular diet, they grew in height and became sexually mature. It is now recognized that dwarfism in males is frequent around the Mediterranean, where wheat is the staple of life and has been grown for 4,000 years on the same soil, thereby resulting in the depletion of zinc. Professor Robert Henkin first suggested that zinc deficiency might cause hearing-nerve impairment. Assay of the soft tissues of the cochlea and vestibule revealed a zinc level higher than that of any other part of the body. Previously, the eye was considered to have the highest level of zinc of any organ. To diagnose zinc deficiency clinically, we use serum zinc assays made at the Mayo Clinic Trace Element Laboratory. With zinc supplementation in patients who are marginally zinc deficient, there has been improvement in tinnitus and sensorineural hearing loss in about one-third of elderly adults. We believe zinc deficiency is one causation of presbycusis; by recognizing and correcting it, a progressive hearing loss can be arrested.

  14. A case report of acampomelic campomelic dysplasia and operative difficulties in cleft palate reconstruction

    Directory of Open Access Journals (Sweden)

    M Pasupathy

    2016-01-01

    Full Text Available Acampomelic campomelic dysplasia (CD is a type of CD (CD; OMIM #114290, a rare form of congenital short-limbed dwarfism and is due to mutations in SOX9 gene family. Characteristic phenotypes of CD include bowing of the lower limbs, a narrow thoracic cage, 11 pairs of ribs, hypoplastic scapulae, macrocephaly, flattened supraorbital ridges and nasal bridge, cleft palate and micrognathia. The bending of the long bones is not an obligatory feature and is absent in about 10% of cases, referred to as acampomelic CD. A child previously diagnosed with acampomelic CD was brought to our outpatient clinic for cleft palate reconstruction. Our neurosurgeon cautioned us against performing surgery with extension of the neck in view of the possibility of producing quadriparesis, due to narrowing of the spinal canal as part of the osseous anomaly noted in the magnetic resonance imaging study of the spine, thus making the anaesthesia, surgical and post-operative procedures difficult. The cleft palate reconstruction was performed with all precautions and was uneventful.

  15. Rare events in earth history include the LB1 human skeleton from Flores, Indonesia, as a developmental singularity, not a unique taxon

    Science.gov (United States)

    Eckhardt, Robert B.; Henneberg, Maciej; Weller, Alex S.; Hsü, Kenneth J.

    2014-08-01

    The original centrally defining features of "Homo floresiensis" are based on bones represented only in the single specimen LB1. Initial published values of 380-mL endocranial volume and 1.06-m stature are markedly lower than later attempts to confirm them, and facial asymmetry originally unreported, then denied, has been established by our group and later confirmed independently. Of nearly 200 syndromes in which microcephaly is one sign, more than half include asymmetry as another sign and more than one-fourth also explicitly include short stature. The original diagnosis of the putative new species noted and dismissed just three developmental abnormalities. Subsequent independent attempts at diagnosis (Laron Syndrome, Majewski osteodysplastic primordial dwarfism type II, cretinism) have been hampered a priori by selectively restricted access to specimens, and disparaged a posteriori using data previously unpublished, without acknowledging that all of the independent diagnoses corroborate the patent abnormal singularity of LB1. In this report we establish in detail that even in the absence of a particular syndromic diagnosis, the originally defining features of LB1 do not establish either the uniqueness or normality necessary to meet the formal criteria for a type specimen of a new species. In a companion paper we present a new syndromic diagnosis for LB1.

  16. Is our Future Written in the Geological Record of Oceanic Anoxic Events? The Calcareous Nannoplankton Perspective (Invited)

    Science.gov (United States)

    Erba, E.

    2013-12-01

    Cenomanian OAE2 and detected major changes in nannofossil abundance, composition and biomineralization, separating most-, intermediate-, and least-tolerant taxa. The T-OAE, OAE1a and OAE2 share similarities in nannoplankton changes, although some differential response was detected. Nannofossil indices highlight strong variability in climate and fertility during OAEs and point to ocean acidification as central distress to calcifying plankton. In general, calcareous phytoplankton show a major calcification failure of heavily calcified forms, ephemeral coccolith dwarfism and malformation possibly representing most remarkable species-specific adjustments to survive surface water acidity. However, different patterns and degree of calcification reduction, dwarfism and malformation during OAEs suggest unequal volcanic CO2 rates, pulses and amount. The duration of OAEs seems a direct measure of LIP-derived excess CO2, hampering biocalcification while turning the oceans into an immense anoxic pool. Changes in ocean chemistry, structure, and fertility during LIP formation might explain observed tempo and mode of nannoplankton evolution: major origination episodes might result from magmas especially enriched in biogeochemically important elements from the mantle.

  17. 一例成骨不全Ⅱ型高危胎儿的产前基因诊断%Prenatal gene diagnosis of a high-risk fetus with osteogenesis imperfecta type Ⅱ

    Institute of Scientific and Technical Information of China (English)

    艾阳; 唐佳; 方群; 吴晓昀; 郭奕斌

    2011-01-01

    目的 对广东一疑似致死性侏儒症或成骨不全Ⅱ型的高危胎儿实施产前基因诊断,以阐明胎儿骨发育异常的真实病因,及时预防患胎出生.方法 对经超声检查初诊为致死性侏儒症或成骨不全、已孕25周的高危胎儿,在抽取脐血制备DNA模板后,采用PCR-DNA直接测序法,分别对胎儿的FGFR3基因和COL1A1基因进行突变检测,然后对所发现的突变进行分析和鉴定.结果 FGFR3基因未发现病理性突变,而COL1A1基因发现一典型的杂合错义突变(c.3065 G>T,PG1022V),经查HGMD数据库证实为成骨不全Ⅱ型的致病性突变.结论 (1)此高危胎儿为成骨不全Ⅱ型患胎,应及时终止妊娠(胎儿已经引产,经复查证实与产前基因诊断结果完全一致).(2)在超声初诊基础上,采用产前基因诊断可快速、有效对高危胎儿做出确诊,为出生缺陷的预防提供技术保障.%Objective To clarify the real pathogeny of the dysostoses of fetuses ,the prenatal gene diagnosis of a Guangdong high-risk fetus suspected with osteogenesis imperfecta type II or thanatophoric dwarfism was carried out, which stopped the birth of the suffering fetuses. Methods The high-risk fetus of 25 weeks was preliminarily diagnosed with thanatophoric dwarfism or osteogenesis imperfecta by ultrasonic test. The cord blood was extracted to make preparation for DNA template ,PCR-DNA sequencing was used to detect the mutation of FGFR3 gene and COL1A1 gene,then the mutations were analyzed and identified. Results There was no pathological mutation on the FGFR3 gene. There was a c. 3065 G > T,p. G1022V heterozygosis missense mutation on the COL1A1 gene,which caused osteogenesis imperfecta type II ;it was already reported on the HGMD. Conclusions (1) The high-risk fetus suffer with osteogenesis imperfecta -Ⅱ ,which should be induced labour (the fetus had been induced labour already. The result of prenatal gene diagnosis was completely accordance with the result of

  18. 精氨酸、可乐定、精氨酸联合左旋多巴不同激发试验对GH分泌的影响%Influence of different motivation test with arginine,clonidine,arginine combined with L-dopa,clonidine in GH secretion

    Institute of Scientific and Technical Information of China (English)

    吴红玲; 陈雪梅; 陈爱劳; 钟林; 钟梅珍; 刘军平; 罗锦成

    2015-01-01

    Objective To compare the effect of different motivation test with arginine,clonidine, arginine combined with L-dopa in GH secretion of dwarfism children. Methods 60 GH children patients from June 2013 to December 2014 of our hospital were selected and retrospectively analyzed.Patients were divided into GHD group (n=30) and non GHD group (n=30) by diagnosis results.Patients were treated with drug motivation test by using arginine,clonidine,arginine combined with L-dopa.The impact of different motivation test on GH secretion was compared. Results The peak value of arginine,clonidine and arginine combined with L-dopa in GHD group were lower than non GHD group,and the dif-ferences were statistically significant (P<0.05).The peak value of arginine combined with L-dopa in two groups were higher than arginine and clonidine,and the differences were statistically significant (P<0.05).The sensitivity,specificity and accuracy of arginine combined with L-dopa were higher than arginine and clonidine,and the differences were sta-tistically significant (P<0.05). Conclusion The sensitivity,specificity and accuracy of arginine combined with L-dopa is higher.The clinical value is higher in checking GH secretion of dwarfism children.%目的:比较精氨酸、可乐定、精氨酸联合左旋多巴不同激发试验对矮小症儿童脑垂体生长激素(GH)分泌的影响。方法选取我院自2013年6月~2014年12月收治的GH患儿60例进行回顾性分析,根据诊断结果进行分组,共分为两组:生长激素缺乏症(GHD)组(30例)和非GHD组(30例),对其进行精氨酸药物激发试验、可乐定药物激发试验精、氨酸联合左旋多巴药物激发试验,比较不同激发试验对GH分泌的影响。结果 GHD组精氨酸联合左旋多巴、精氨酸、可乐定的峰值均低于非GHD组,差异有统计学意义(P<0.05)。两组精氨酸联合左旋多巴的峰值均高于精氨酸、可乐定,差异有统计学意义(P<0.05)

  19. Le mythe du microcèbe primitif The myth of the primitive mouse lemur

    Directory of Open Access Journals (Sweden)

    Fabien Génin

    2011-10-01

    criticise this almost mythical view, which is neither supported by the fossil record nor by the most recent phylogenies. We propose the alternative hypothesis of a reduction of body size, or dwarfism, a phenomenon known to occur frequently on islands, and in isolated regions subject to El Niño-related unpredictable droughts. We confirm Gould’s model of progenesis, which explains dwarfism by hypervariability leading to acceleration of life history. Cheirogaleids appear as paedomorphic dwarfs compared to their sister-taxon, the Lepilemuridae (Lepilemur. They probably experienced at least 3 independent events of dwarfing which lead to parallel changes in the proportions of the head and limbs (allometry. The first one (dwarfing has led to a decrease in the size of body and limbs, without any significant change in cranial form (with the exception of teeth in the largest forms Phaner, Mirza, and the largest forms of the genus Cheirogaleus. The second (hyper-dwarfing has led to parallel changes in cranial form in the smallest taxa (Allocebus, Microcebus and the smaller forms of the genus Cheirogaleus, associated with typical paedomorphic traits (large eyes and small, pointed snout. This new interpretation explains many unique characteristics of this group of lemurs, in particular their rapid life histories.

  20. Successful Wide Hybridization and Introgression Breeding in a Diverse Set of Common Peppers (Capsicum annuum) Using Different Cultivated Ají (C. baccatum) Accessions as Donor Parents.

    Science.gov (United States)

    Manzur, Juan Pablo; Fita, Ana; Prohens, Jaime; Rodríguez-Burruezo, Adrián

    2015-01-01

    Capsicum baccatum, commonly known as ají, has been reported as a source of variation for many different traits to improve common pepper (C. annuum), one of the most important vegetables in the world. However, strong interspecific hybridization barriers exist between them. A comparative study of two wide hybridization approaches for introgressing C. baccatum genes into C. annuum was performed: i) genetic bridge (GB) using C. chinense and C. frutescens as bridge species; and, ii) direct cross between C. annuum and C. baccatum combined with in vitro embryo rescue (ER). A diverse and representative collection of 18 accessions from four cultivated species of Capsicum was used, including C. annuum (12), C. baccatum (3), C. chinense (2), and C. frutescens (1). More than 5000 crosses were made and over 1000 embryos were rescued in the present study. C. chinense performed as a good bridge species between C. annuum and C. baccatum, with the best results being obtained with the cross combination [C. baccatum (♀) × C. chinense (♂)] (♀) × C. annuum (♂), while C. frutescens gave poor results as bridge species due to strong prezygotic and postzygotic barriers. Virus-like-syndrome or dwarfism was observed in F1 hybrids when both C. chinense and C. frutescens were used as female parents. Regarding the ER strategy, the best response was found in C. annuum (♀) × C. baccatum (♂) crosses. First backcrosses to C. annuum (BC1s) were obtained according to the crossing scheme [C. annuum (♀) × C. baccatum (♂)] (♀) × C. annuum (♂) using ER. Advantages and disadvantages of each strategy are discussed in relation to their application to breeding programmes. These results provide breeders with useful practical information for the regular utilization of the C. baccatum gene pool in C. annuum breeding.