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Sample records for autosomal dominant inheritance

  1. Frontometaphyseal dysplasia: evidence for autosomal dominant inheritance.

    Science.gov (United States)

    Kassner, E G; Haller, J O; Reddy, V H; Mitarotundo, A; Katz, I

    1976-12-01

    Frontometaphyseal dysplasia is a syndrome that encompasses cranial hyperostosis, abnormal tubulation of cylindrical bones, and other skeletal and extraskeletal abnormalities. The most striking features are overgrowth of the supraorbital ridges which results in a Mephistophelian facial appearance and a radiographic configuration of the skull that has been likened to a soldier's helmet. Most patients have severe hearing loss, defective dentition, poorly developed musculature, and joint contractures. Dominant inheritance has been suggested in previous reports, but an appropriate pedigree has been documented in only one family. This paper describes three additional patients in two unrelated families: (1) an 8-year-old boy whose mother has mild metaphyseal dysplasia and several minor skeletal abnormalities that have occurred in patients with the syndrome; and (2) two maternal half-brothers. These cases provide additional evidence that frontometaphyseal dysplasia is an autosomal dominant trait with variable penetrance. PMID:998829

  2. Cleidocranial Dysplasia with Autosomal Dominant Inheritance Pattern

    OpenAIRE

    Bhargava, P.; Khan, S; Sharma, R.; Bhargava, S.

    2014-01-01

    Cleidocranial dysplasia (CCD) is an autosomal dominant disease with a wide range of expression, characterized by clavicular hypoplasia, retarded cranial ossification, delayed bone and teeth development, supernumerary teeth, stomatognathic, craniofacial and skeletal abnormalities. This paper presents a case of CCD in a female with brachycephalic skull, depressed frontal bone and nasal bridge, hypoplastic middle one-third of face with mandibular prognathism and hyper mobility of both shoulders ...

  3. Cleidocranial dysplasia with autosomal dominant inheritance pattern.

    Science.gov (United States)

    Bhargava, P; Khan, S; Sharma, R; Bhargava, S

    2014-07-01

    Cleidocranial dysplasia (CCD) is an autosomal dominant disease with a wide range of expression, characterized by clavicular hypoplasia, retarded cranial ossification, delayed bone and teeth development, supernumerary teeth, stomatognathic, craniofacial and skeletal abnormalities. This paper presents a case of CCD in a female with brachycephalic skull, depressed frontal bone and nasal bridge, hypoplastic middle one-third of face with mandibular prognathism and hyper mobility of both shoulders with associated radiographic features. Odontologist is often the first professional who patient of CCD approaches, since there is a delay in the eruption or absence of permanent teeth. The premature diagnosis allows a scope for proper treatment modalities, offering a better life quality for patient. PMID:25184084

  4. Autosomal dominant inheritance Caffey-Silverman disease hyperostosis corticalis infantum

    International Nuclear Information System (INIS)

    A case of Caffey-Silverman disease is described in an infant aged 4.5 months. The case was erroneously diagnosed in the initial stage of the disease as osteitis. The correct diagnosis was established after radiological examination of the skeleton. The pathological lesions involved the mandible, both clavicles, all ribs, left shoulder blade, both radial bones and left ulna. Follow-up radiological examination after 12 months demonstrated nearly complete disappearance of the previously observed skeletal changes. At the age of 18 months the condition of the child was good and its development was normal. Radiological changes indicating past Caffey-Silverman disease were disclosed in the mother and maternal grandmother of the child. This indicates an autosomal dominant type of inheritance of the disease. (Author)

  5. Vestibular function in families with inherited autosomal dominant hearing loss

    OpenAIRE

    Street, Valerie A.; Kallman, Jeremy C.; Strombom, Paul D.; Bramhall, Naomi F; Phillips, James O.

    2008-01-01

    The inner ear contains the developmentally related cochlea and peripheral vestibular labyrinth. Given the similar physiology between these two organs, hearing loss and vestibular dysfunction may be expected to occur simultaneously in individuals segregating mutations in inner ear genes. Twenty-two different genes have been discovered that when mutated lead to non-syndromic autosomal dominant hearing loss. A review of the literature indicates that families segregating mutations in 13 of these ...

  6. Description of familial keloids in five pedigrees: evidence for autosomal dominant inheritance and phenotypic heterogeneity

    Directory of Open Access Journals (Sweden)

    Kleta Robert

    2009-07-01

    Full Text Available Abstract Background Familial keloids have been reported, having either autosomal dominant or autosomal recessive inheritance. We wished to determine the inheritance pattern and phenotype of keloids among multigenerational families, as a prelude to a positional mapping strategy to identify candidate genes. Methods We studied three African American families, one Afro-Caribbean family and one Asian-American family. Phenotyping including assessing all patients for the presence, distribution, and appearance of keloids, together with the timing of keloid onset and provocative factors. The clinical trial was registered at clinicaltrials.gov (NCT 00005802. Results Age of keloid onset varied considerably within families, but commonly occurred by the second decade. The fraction of affected individuals was 38%, 45%, 62%, 67% and 73% among the five families respectively. Keloid severity and morphology differed within and between families. A novel finding is that certain families manifest keloids in distinct locations, with one family showing an excess of extremity keloids and two families showing an excess of axilla-groin keloids. Conclusion Familial keloids appear to most commonly manifest autosomal dominant or semidominant inheritance, and there may be familial patterns of keloid distribution.

  7. [Retracted] Clinical, pathological and genetic characteristics of autosomal dominant inherited dynamin 2 centronuclear myopathy.

    Science.gov (United States)

    Liu, Xinhong; Wu, Huamin; Gong, Jian; Wang, Tao; Yan, Chuanzhu

    2016-07-01

    We wish to retract our article entitled 'Clinical, pathological and genetic characteristics of autosomal dominant inherited dynamin 2 centronuclear myopathy' published in Molecular Medicine Reports 13: 4273-4278, 2016. The article was submitted by the first author, Xinhong Liu, without the prior knowledge of the corresponding author, Chuanzhu Yan, or the other authors included on the paper. Furthermore, the details of the paper were not discussed by the authors prior to the submission, and all are in agreement that the paper contains data therein (and interpretations thereof) which are either inaccurate or inappropriate. All the authors agree to this retraction, and we apologize for the inconvenience caused in this regard.[the original article was published in the Molecular Medicine Reports 13: 4273-4278, 2016; DOI: 10.3892/mmr.2016.5047]. PMID:27176730

  8. Chorioretinal dysplasia-microcephaly-mental retardation syndrome : Another family with autosomal dominant inheritance

    NARCIS (Netherlands)

    Hordijk, R; VandeLogt, F; Houtman, WA; VanEssen, AJ

    1996-01-01

    We describe a boy and his father with the chorioretinal dysplasia-microcephaly-mental retardation syndrome (CDMMS). Our report extends the phenotypic spectrum of autosomal dominant CDMMS by describing microphthalmia for the first time in an autosomal dominant family. The boy was also severely mental

  9. A three-generation family with idiopathic facial palsy suggesting an autosomal dominant inheritance with high penetrance

    DEFF Research Database (Denmark)

    Larsen, Christian Grønhøj; Gyldenløve, Mette; Jønch, Aia Elise;

    2015-01-01

    Idiopathic facial palsy (IFP), also known as Bell's palsy, is a common neurologic disorder, but recurrent and familial forms are rare. This case series presents a three-generation family with idiopathic facial palsy. The mode of inheritance of IFP has previously been suggested as autosomal dominant...

  10. Clinical, pathological and genetic characteristics of autosomal dominant inherited dynamin 2 centronuclear myopathy.

    Science.gov (United States)

    Liu, Xinhong; Wu, Huamin; Gong, Jian; Wang, Tao; Yan, Chuanzhu

    2016-05-01

    The aim of the present study was to report on a family with pathologically and genetically diagnosed autosomal dominant inherited centronuclear myopathy (CNM). In addition, this study aimed to investigate the clinical, pathological and molecular genetic characteristics of the disease. This pedigree was traced back three generations, four patients underwent neurological examination, two patients underwent muscle biopsy, and eight family members were subjected to dynamin 2 (DNM2) gene mutation analysis. DNM2 mutations were detected in seven family members, of which four patients exhibited DNM2 mutation‑specific clinical and pathological features. Lower extremity weakness was the predominant symptom of these patients, however, proximal and distal lower extremity involvement was inconsistent. All patients exhibited marked systematic muscle atrophy and various degrees of facial muscle involvement. The patients presented the typical pathological changes of CNM, and their muscle tissues were heavily replaced by adipose tissue, with clustered distribution of muscle fibers as another notable feature. DNM2‑CNM patients of this pedigree exhibited heterogeneous clinical and pathological features, providing a basis for further molecular genetic analysis. PMID:27035234

  11. Autosomal dominant isolated ('uncomplicated') microcephaly.

    OpenAIRE

    Merlob, P; Steier, D; Reisner, S H

    1988-01-01

    A large family (13 affected members in three generations) is reported in which isolated microcephaly occurred without any other dysmorphic or neurological abnormalities. The family pedigree confirms the autosomal dominant mode of inheritance with incomplete penetrance, including one example of male to male transmission and the occurrence of a non-manifesting heterozygote resulting in a 'skipped generation'. There is considerable variation in the phenotypic expression of autosomal dominant mic...

  12. Autosomal dominant mesomandibular fibro-osseous dysplasia: a self-resolving inherited fibro-osseous lesion of the jaws

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    Ioannis eKoutlas

    2012-12-01

    Full Text Available A hereditary congenital condition characterized by a fibro-osseous lesion sharing some features with fibrous dysplasia and affecting the middle aspect of the mandible is presented. The condition was initially described as congenital monostotic fibrous dysplasia in two siblings, a male and a female. However, there is sufficient evidence that the disorder is autosomal dominant since it has been encountered in two of four children, both males, of the female propositus and one child, a boy, of the male propositus. All patients presented at birth or right after birth with enlargement of the middle part of the mandible. Radiographs from affected individuals have shown mesomandibular enlargement with irregular trabeculation akin of ground-glass appearance. Histologically, samples from all patients revealed woven bone proliferation in a cellular fibroblastic stroma. Interestingly, the originally described siblings, now in their 30s, have no evidence of jaw lesions either radiographically or clinically, thus indicating that the condition is self-limiting or self-resolving. An autosomal dominant mode of inheritance with apparent male predilection is favored. The molecular basis of this condition is currently unknown. However, the location of the lesions in the middle aspect of the mandible suggests dysregulation of Bone Morphogenetic Protein signaling since BMPs regulate mandibular morphogenesis in utero, particularly in the medial region as well as postnatal bone remodeling. Immunohistochemical evaluation for a BMP-binding protein Twisted Gastrulation revealed mosaic pattern of staining, with some cells, including osteoclasts, strongly stained and others exhibiting faint or no staining, thus supporting active regulation of BMP signaling within the lesion. Future investigations will determine if dysregulation of BMP signaling plays a causative role or rather reflects secondary activation of repair mechanisms and/or bone remodeling.

  13. Maternally inherited autosomal dominant intellectual disability caused by 16p13.3 microduplication.

    Science.gov (United States)

    Lee, Cha Gon; Cho, Eunhae; Ahn, Young Min

    2016-04-01

    A 16p13.3 duplication syndrome has been recently suggested to be a novel recognizable syndrome as a reciprocal microduplication disease of Rubinstein-Taybi syndrome. The CREBBP gene is believed to be the dosage-sensitive critical gene responsible for the reciprocal duplication and deletion syndrome. Descriptions so far have been de novo. Here, we report a very rare case of a maternally inherited a -1 Mb sized duplication on 16p13.3 identified by SNP array testing. The patient showed moderate intellectual disability, normal growth, and characteristic facial features. The patient's mother also had mild intellectual disability, normal growth, camptodactyly, proximally implanted small thumbs, and distinctive facial features. The study provides additional information that furthers the understanding and delineation of 16p13.3 duplication syndrome. PMID:26873618

  14. Spectrum of sonographic changes in hereditary motor and sensory neuropathy with autosomal dominant and X-linked inheritance

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    E. S. Naumova

    2016-01-01

    Full Text Available Background. In the recent years interest towards nerve sonography has largely increased, specifically in terms of differentiating types of hereditary motor and sensory neuropathy (HMSN. The diagnostic possibilities of high-resolution ultrasound (HRUS compared to standard neurophysiological tools in the peripheral nerve disorders is still a matter of debate.Objectives. Analysis of quantitative and qualitative ultrasound changes of limb nerves in patients with HMSN type 1 and its comparison with anthropometric and nerve conduction study data.Materials and methods. 44 HMSN patients were analyzed: 16 men, mean age 35,9 ± 6,8 years; 16 (37 % with autosomal dominant type 1А, 11 (25 % – with 1В type and 17 (38 % with Х-linked inheritance. Control group included 44 subjects, 16 male; mean age 35,9 ± 6,8 years. HRUS parameters were analyzed bilaterally on the selected levels: cross-sectional area (CSA, visual cross sectional and longitudinal patterns of the median and ulnar nerves, C5, C6, C7 spinal nerves, tibial, peroneal and sciatic nerves. HRUS parameters were compared to standard anthropometric data, nerve conduction velocity and CMAP amplitude.Results. In all HMSN cases CSA was enlarged compared to healthy controls. Greater changes were found in patients with autosomal dominant inheritance. CSA enlargement in С5, С6, С7 spinal nerves was found in patients with HMSN 1A, С6, С7 – in HMSN 1В, С6 – in HMSN 1X, confirming the necessity to include those nerves in the sonographic protocol in patients with HMSN. Three qualitative cross sectional and longitudinal patterns of the investigated arm nerves were identified, distinct for each of the HMSN type. Absence of significant differences in CSA of the upper limb nerves among analyzed types of HMSN makes it unreliable as the differential parameter, opposite to the defined sonographic patterns. Methodological issues and absence of significant quantitative and qualitative data

  15. Epiphyseal osteochondromas with autosomal dominant inheritance and multiple parosteal bone proliferations

    International Nuclear Information System (INIS)

    The familial cases of dysplasia epiphysealis hemimelica (DEH), or Trevor's disease, are thought to represent dominant carpotarsal osteochondromatosis (DCO). Only three families affected by DCO have been reported so far in the literature. We report a fourth family: a 10-year-old girl, her father, and his cousin. Unlike the other reported cases of DCO this family had no carpal or upper limb epiphyseal osteochondromas and many of the other reported associations. The only consistent associated finding in our cases was the presence of multiple parosteal osteochondromatous proliferations. The findings of our cases are, therefore, unique in many ways. These cases may represent a variant of dominant carpotarsal osteochondromatosis or may represent a new entity. (orig.)

  16. Autosomal-dominant inheritance of the prothrombin gene mutation in a Puerto Rican family: A case study.

    Science.gov (United States)

    Morales-Borges, Raúl H

    2012-12-01

    Splenic infarction is rare and the prothrombin gene mutation (PGM) is not commonly observed in Puerto Rico. PGM is present in 1% of the general population, and in 7% of the people with deep venous thrombosis (DVT); it is found in up to 40% of patients with splenic-portal-mesenteric thrombosis. Our study has identified a Puerto Rican family of four generations whose members all have inherited PGM in an autosomal dominant manner. The eldest member of the family, an 82-year-old male, presented with DVT of the lower extremity. The man's 62-year-old daughter had suffered a splenic infarction; his 37-year-old grandson presented with superficial and deep vein thrombosis (SDVT), and his great-grandson of 8 years was asymptomatic at the time of the report. This is the second report of PGM as the cause of a hypercoagulable state and the first reported PGM-related splenic infarction in Puerto Rico. We need to test for genetic hypercoagulable states in the members of Puerto Rican families with thromboembolism. Once testing has revealed the existence of such states in a given family, it is important that the family members receive genetic counseling. PMID:23844473

  17. Autosomal Dominant Transmission of Accessory Navicular

    OpenAIRE

    Dobbs, Matthew B.; Walton, Tim

    2004-01-01

    The accessory navicular bone is one of the most symptomatic bones of the foot. Although it has been reported to be present in various members of the same family, there is a lack of knowledge about its inheritance pattern. We report two large pedigrees in which accessory navicular is inherited in an autosomal dominant fashion with incomplete penetrance.

  18. Autosomal-dominant osteopetrosis: An incidental finding

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    Rajathi Maria

    2010-01-01

    Full Text Available Osteopetrosis is a descriptive term that refers to a group of rare, heritable disorders of the skeleton. Osteopetrotic conditions vary greatly in their presentation and severity, from just as an incidental finding on radiographs to causing life-threatening complications such as bone marrow suppression. It is caused by failure of osteoclast development and function. Osteopetrosis can be inherited as autosomal-recessive, autosomal-dominant or as X-linked traits, with the most severe forms being the autosomal-recessive ones. The severity of the disease is mild to moderate in the autosomal-dominant forms, with normal life expectancy. Diagnosis is largely based on clinical and radiographic evaluation. The present paper reports a case of autosomal-dominant osteopetrosis complicated by osteomyelitis with a short review of the condition.

  19. Autosomal dominant rolandic epilepsy with speech dyspraxia.

    Science.gov (United States)

    Scheffer, I E

    2000-01-01

    Autosomal Dominant Rolandic Epilepsy with Speech Dyspraxia (ADRESD) is a rare disorder which highlights the relationship between Benign Rolandic Epilepsy (BRE) and speech and language disorders. Subtle speech and language disorders have recently been well characterised in BRE. ADRESD is associated with long term, more severe speech and language difficulties. The time course of rolandic epilepsy in ADRESD is typical of that of BRE. ADRESD is inherited in an autosomal dominant manner with anticipation. It is postulated that the anticipation may be due to an, as yet unidentified, triplet repeat expansion in a gene for rolandic epilepsy. BRE follows complex inheritance but it is possible that ADRESD may hold some valuable clues to the pathogenesis of BRE. PMID:11231219

  20. Mutations in PDGFRB Cause Autosomal-Dominant Infantile Myofibromatosis

    OpenAIRE

    Martignetti, John A.; Tian, Lifeng; Li, Dong; Ramirez, Maria Celeste M.; Camacho-Vanegas, Olga; Camacho, Sandra Catalina; Guo, Yiran; Zand, Dina J.; Bernstein, Audrey M.; Masur, Sandra K.; Kim, Cecilia E.; Otieno, Frederick G.; Hou, Cuiping; Abdel-Magid, Nada; Tweddale, Ben

    2013-01-01

    Infantile myofibromatosis (IM) is a disorder of mesenchymal proliferation characterized by the development of nonmetastasizing tumors in the skin, muscle, bone, and viscera. Occurrence within families across multiple generations is suggestive of an autosomal-dominant (AD) inheritance pattern, but autosomal-recessive (AR) modes of inheritance have also been proposed. We performed whole-exome sequencing (WES) in members of nine unrelated families clinically diagnosed with AD IM to identify the ...

  1. Autosomal-dominant Alzheimer's disease: a review and proposal for the prevention of Alzheimer's disease

    OpenAIRE

    Bateman, R.J.; Aisen, P.S.; De Strooper, B.; Fox, N C; Lemere, C. A.; Ringman, J.M.; Salloway, S; Sperling, R. A.; Windisch, M.; Xiong, C.

    2011-01-01

    Autosomal-dominant Alzheimer's disease has provided significant understanding of the pathophysiology of Alzheimer's disease. The present review summarizes clinical, pathological, imaging, biochemical, and molecular studies of autosomal-dominant Alzheimer's disease, highlighting the similarities and differences between the dominantly inherited form of Alzheimer's disease and the more common sporadic form of Alzheimer's disease. Current developments in autosomal-dominant Alzheimer's disease are...

  2. Familial co-segregation of Coffin-Lowry syndrome inherited from the mother and autosomal dominant Waardenburg type IV syndrome due to deletion of EDNRB inherited from the father.

    Science.gov (United States)

    Loupe, Jacob; Sampath, Srirangan; Lacassie, Yves

    2014-10-01

    We report an African-American family that was identified after the proposita was referred for diagnostic evaluation at 4½ months with a history of Hirschsprung and dysmorphic features typical of Waardenburg syndrome (WS). Family evaluation revealed that the father had heterochromidia irides and hypertelorism supporting the clinical diagnosis of WS; however, examination of the mother revealed characteristic facial and digital features of Coffin-Lowry syndrome (CLS). Molecular testing of the mother identified a novel 2 bp deletion (c.865_866delCA) in codon 289 of RPS6KA3 leading to a frame-shift and premature termination of translation 5 codons downstream (NM_004586.2:p.Gln289ValfsX5). This deletion also was identified in the proposita and her three sisters with a clinical suspicion of CLS, all of whom as carriers for this X-linked disorder had very subtle manifestations. The molecular confirmation of WS type 4 (Shah-Waardenburg; WS4) was not as straightforward. To evaluate WS types 1-4, multiple sequential molecular tests were requested, including Sanger sequencing of all exons, and deletion/duplication analysis using MLPA for PAX3, MITF, SOX10, EDN3 and EDNRB. Although sequencing did not identify any disease causing variants, MLPA identified a heterozygous deletion of the entire EDNRB in the father. This deletion was also found in the proposita and the oldest child. Since the heterozygous deletion was the only change identified in EDNRB, this family represents one of the few cases of an autosomal dominant inheritance of WS4 involving the endothelin pathway. Altogether, clinical evaluation of the family revealed one child to be positive for WS4 and two positive for CLS, while two children were positive for both diseases simultaneously (including the proposita) while another pair test negative for either disease. This kinship is an example of the coincidence of two conditions co-segregating in one family, with variable phenotypes requiring molecular testing to

  3. Genetics Home Reference: autosomal dominant vitreoretinochoroidopathy

    Science.gov (United States)

    ... Diagnosis & Management These resources address the diagnosis or management of autosomal dominant vitreoretinochoroidopathy: American Foundation for the Blind: Living with Vision Loss Genetic Testing Registry: Vitreoretinochoroidopathy dominant These resources ...

  4. Phenotypic Variation of Autosomal-Dominant Corticobasal Degeneration

    OpenAIRE

    H. Jung, Hans; Bremer, Juliane; Streffer, Johannes; Virdee, Kanwar; Grazia Spillantini, Maria; Anthony Crowther, R.; Brugger, Peter; Van Broeckhoven, Christine; Aguzzi, Adriano; Tolnay, Markus

    2012-01-01

    Neurodegenerative tauopathies may be inherited as autosomal-dominant disorders with variable clinicopathological phenotypes, and causative mutations in the microtubule-associated protein tau (MAPT) gene are not regularly seen. Herein, we describe a patient with clinically typical and autopsy-proven corticobasal degeneration (CBD). Her mother was diagnosed to have Parkinson's disease, but autopsy showed CBD pathology as in the index patient. The sister of the index patient had the clinical sym...

  5. Autosomal dominant polycystic kidney disease: New insights into treatment

    OpenAIRE

    Imed Helal

    2013-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the world′s most common inherited kidney disease. An increasing number of animal and human studies have enhanced our understanding of the molecular and cellular pathology of ADPKD. New treatment options are being tested in clinical trials in spite of the failure of mammalian target of rapamycin inhibitor therapy. The main and most effective therapy remains control of hypertension by renin-angiotensin-aldosterone system (RAAS) blockade. T...

  6. Dominant inheritance of overo spotting in paint horses.

    Science.gov (United States)

    Bowling, A T

    1994-01-01

    Analysis of selected studbook records of the American Paint Horse Association, consisting of 687 foals sired by 13 overo stallions from non-overo mares, supports the inheritance of overo spotting as an autosomal dominant gene. More than one gene may control patterns registered as overo. Additional studies are necessary to explain the sporadic occurrence of overo spotting from nonspotted quarter horse parents and to confirm the inheritance of overo spotting in other breeds. PMID:8014463

  7. Oculodentodigital dysplasia: study of ophthalmological and clinical manifestations in three boys with probably autosomal recessive inheritance.

    Science.gov (United States)

    Frasson, Maria; Calixto, Nassim; Cronemberger, Sebastião; de Aguiar, Regina Amélia Lopes Pessoa; Leão, Letícia Lima; de Aguiar, Marcos José Burle

    2004-09-01

    Oculodentodigital dysplasia (ODDD) is a rare inherited disorder affecting the development of the face, eyes, teeth, and limbs. The majority of cases of ODDD are inherited as an autosomal dominant condition. There are few reports of probable autosomal recessive transmission. Affected patients exhibit a distinctive physiognomy with a narrow nose, hypoplastic alae nasi, and anteverted nostrils, bilateral microphthalmos, and microcornea. Sometimes iris anomalies and secondary glaucoma are present. There are malformations of the distal extremities such as syndactyly. In addition, there are defects in the dental enamel with hypoplasia and yellow discoloration of the teeth. Less common features include hypotrichosis, intracranial calcifications, and conductive deafness secondary to recurrent otitis media. We describe three brothers with ODDD. Their parents are first cousins and present no features of ODDD. These data are in favor of autosomal recessive inheritance and suggest genetic heterogeneity for this entity. PMID:15512999

  8. Autosomal Dominant Hereditary Macrothrombocytopenia in an Iranian Family

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    M Isadiar

    2006-06-01

    Full Text Available Objective: Thrombocytopenia is the most common hemostatic disease of the newborn. Inherited giant platelet syndromes are a heterogeneous group of rare bleeding disorders. In this paper we describe here a female neonate with autosomal dominant hereditary macrothrombocytopenia. Case report: A female neonate was referred to our center due to mucosal hemorrhage (nasal and gastrointestinal bleeding. Her mother’s platelet count was normal. However her father, paternal uncle and two paternal aunts also had severe thrombocytopenia and all of them underwent splenectomy for idiopathic thrombocytopenic purpura (ITP. Considering all clinical and laboratory findings, autosomal dominant hereditary macrothrombocytopenia was the best diagnosis. Conclusion: It is important to differentiate between congenital and acquired thrombocytopenia to avoid unneeded and potentially harmful therapy. Treatment is not usually necessary, however some patients with hereditary thrombocytopenia may benefit from bone marrow transplantation.

  9. Evidence for autosomal recessive inheritance in SPG3A caused by homozygosity for a novel ATL1 missense mutation

    OpenAIRE

    Khan, Tahir Naeem; Klar, Joakim; Tariq, Muhammad; Anjum Baig, Shehla; Malik, Naveed Altaf; Yousaf, Raja; Baig, Shahid Mahmood; Dahl, Niklas

    2014-01-01

    Hereditary spastic paraplegias (HSPs) comprise a heterogeneous group of disorders characterized by progressive spasticity and weakness of the lower limbs. Autosomal dominant and ‘pure' forms of HSP account for ∼80% of cases in Western societies of whom 10% carry atlastin-1 (ATL1) gene mutations. We report on a large consanguineous family segregating six members with early onset HSP. The pedigree was compatible with both autosomal dominant and autosomal recessive inheritance. Whole-exome seque...

  10. Genetics Home Reference: autosomal dominant congenital stationary night blindness

    Science.gov (United States)

    ... stationary night blindness autosomal dominant congenital stationary night blindness Enable Javascript to view the expand/collapse boxes. ... Close All Description Autosomal dominant congenital stationary night blindness is a disorder of the retina , which is ...

  11. Mitochondrial anomalies in a Swiss family with autosomal dominant myoglobinuria

    Energy Technology Data Exchange (ETDEWEB)

    Martin-du Pan, R.C. [Univ. Hospital, Geneva (Switzerland); Favre, H.; Junod, A. [Univ. Hospital, Geneva (Switzerland)] [and others

    1997-04-14

    We report on a Swiss family in which 10 individuals of both sexes in 4 successive generations suffered from myoglobinuria, precipitated by febrile illness. It is the second family described with autosomal dominant inheritance of myoglobinuria. Four individuals suffered acute renal failure, which in two was reversible only after dialysis. In a recent case, a mitochondrial disorder was suspected because of an abnormal increase in lactate levels during an exercise test and because of a subsarcolemmal accumulation of mitochondria in a muscle biopsy, associated with a lack of cytochrome C oxidase in some muscle fibers. No mutation in the mitochondrial DNA was identified. Along with the inheritance pattern, these findings suggest that the myoglobinuria in this family is caused by a nuclear-encoded mutation affecting the respiratory chain. 22 refs., 2 figs.

  12. MRI of autosomal dominant pure spastic paraplegia

    DEFF Research Database (Denmark)

    Krabbe, K; Nielsen, J E; Fallentin, E;

    1997-01-01

    callosum on one midsagittal slice and the area of the brain on one axial slice were measured and a "corpus-callosum index" expressing the size of the corpus callosum relative to that of the brain was calculated. Cross-sectional areas and anteroposterior and transverse diameters of the spinal cord at the...... levels of C 2, C 5, T 3, T 6, T 9 and T 11 were measured. No significant differences between patients and controls were found on qualitative evaluation of the images. The patients had a significantly smaller corpus callosum and "corpus-callosum index" than controls. This finding, not reported previously......We examined 16 patients with autosomal dominant pure spastic paraplegia (HSP) and 15 normal controls matched for age and sex using MRI of the brain and spinal cord. Images were assessed qualitatively by two independent radiologists, blinded to the clinical diagnosis. Areas of the brain and corpus...

  13. Nutraceutical for Autosomal Dominant Polycystic Kidney Disease Therapy.

    Science.gov (United States)

    Yuajit, Chaowalit; Chatsudthipong, Varanuj

    2016-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder caused by mutations of either PKD1 or PKD2 gene. Cyst formation initiates from a combination of abnormal cell proliferation along with enhanced fluid secretion. ADPKD is characterized by the progressive enlargement of cysts which destroy the renal parenchymal cells, resulting in renal failure. Currently, there is no effective treatment for this disease. Interestingly, several relevant therapeutic effects of herbal medicine relevant to pathogenic process of ADPKD have urged the researchers to search for potential candidate herb as nutraceutical for ADPKD therapy. Up to now, several natural compounds, such as triptolide, curcumin, ginkolide B, and steviol (stevia extract) have been shown to be able to retard cyst progression in ADPKD. The detailed mechanism of these compounds showed that triptolide enhanced calcium restoration, curcumin inhibited ERK & p-STAT3 pathways, ginkolide B inhibited Ras/MAPK pathway, and steviol activated AMPK, which inhibited CFTR channel and mTOR pathway in cell and mouse models of PKD. In addition, they are currently inpreclinical and clinical studies, respectively. This review focuses on the pathophysiology of ADPKD and the recent therapeutic approaches, especially a potential use of nutraceutical for the treatment of autosomal dominant polycystic kidney disease. PMID:26817244

  14. Novel therapeutic approaches to autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    LaRiviere, Wells B; Irazabal, Maria V; Torres, Vicente E

    2015-04-01

    Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by the progressive growth of renal cysts that, over time, destroy the architecture of the renal parenchyma and typically lead to kidney failure by the sixth decade of life. ADPKD is common and represents a leading cause of renal failure worldwide. Currently, there are no Food and Drug Administration-approved treatments for the disease, and the existing standard of care is primarily supportive in nature. However, significant advances in the understanding of the molecular biology of the disease have inspired investigation into potential new therapies. Several drugs designed to slow or arrest the progression of ADPKD have shown promise in preclinical models and clinical trials, including vasopressin receptor antagonists and somatostatin analogs. This article examines the literature underlying the rationale for molecular therapies for ADPKD and reviews the existing clinical evidence for their indication for human patients with the disease. PMID:25438190

  15. Autosomal dominant polycystic kidney disease: New insights into treatment

    Directory of Open Access Journals (Sweden)

    Imed Helal

    2013-01-01

    Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is the world′s most common inherited kidney disease. An increasing number of animal and human studies have enhanced our understanding of the molecular and cellular pathology of ADPKD. New treatment options are being tested in clinical trials in spite of the failure of mammalian target of rapamycin inhibitor therapy. The main and most effective therapy remains control of hypertension by renin-angiotensin-aldosterone system (RAAS blockade. This review focuses only on promising therapies, including dual inhibition of RAAS, vasopressin receptor antagonists, increased fluid intake, and blockade of certain receptors of cyclic adenosine monophosphate. Also, the paper reviews what these advances mean to patients and clinicians and elaborates on how these changes can be immediately applied to clinical practice. There is an urgent need for discovery of new therapies targeted toward ADPKD in comparison with therapeutic progress of all other renal diseases.

  16. Bilateral symmetric autosomal dominant sector chorioretinopathy with late maculopathy

    DEFF Research Database (Denmark)

    Fledelius, Hans C; Rosenberg, Thomas

    2012-01-01

    To describe the long-term course of bilateral symmetric autosomal dominant sector chorioretinopathy in a 79-year-old man who was diagnosed at age 31.......To describe the long-term course of bilateral symmetric autosomal dominant sector chorioretinopathy in a 79-year-old man who was diagnosed at age 31....

  17. Familial Paroxysmal Exercise-Induced Dystonia: Atypical Presentation of Autosomal Dominant GTP-Cyclohydrolase 1 Deficiency

    Science.gov (United States)

    Dale, Russell C.; Melchers, Anna; Fung, Victor S. C.; Grattan-Smith, Padraic; Houlden, Henry; Earl, John

    2010-01-01

    Paroxysmal exercise-induced dystonia (PED) is one of the rarer forms of paroxysmal dyskinesia, and can occur in sporadic or familial forms. We report a family (male index case, mother and maternal grandfather) with autosomal dominant inheritance of paroxysmal exercise-induced dystonia. The dystonia began in childhood and was only ever induced…

  18. Genetics Home Reference: autosomal dominant partial epilepsy with auditory features

    Science.gov (United States)

    ... Genetics Home Health Conditions ADPEAF autosomal dominant partial epilepsy with auditory features Enable Javascript to view the ... Accessibility FOIA Viewers & Players U.S. Department of Health & Human Services National Institutes of Health National Library of ...

  19. Evaluation of Nephrolithiasis in Autosomal Dominant Polycystic Kidney Disease Patients

    OpenAIRE

    Nishiura, José L.; Neves, Rodrigo F.C.A.; Eloi, Samara R.M.; Cintra, Susan M.L.F.; Ajzen, Sergio A.; Heilberg, Ita P.

    2009-01-01

    Background and objectives: Nephrolithiasis (LIT) is more prevalent in patients with autosomal dominant polycystic kidney disease (ADPKD) than in the general population. Renal ultrasonography may underdetect renal stones because of difficulties imposed by parenchymal and/or cyst wall calcifications.

  20. PARK1 gene mutation of autosomal dominant Parkinson's disease family

    Institute of Scientific and Technical Information of China (English)

    Ligang Jiang; Guohua Hu; Qiuhui Chen; Ying Zhang; Xinyu Hu; Jia Fan; Lifeng Liu; Rui Guo; Yajuan Sun; Yixhi Zhang

    2011-01-01

    Studies have shown that PARK1 gene is associated with the autosomal dominant inheritance of Parkinson's disease.PARK1 gene contains two mutation sites, namely Ala30Pro and AIa53Thr, which are located on exons 3 and 4, respectively.However, the genetic loci of the pathogenic genes remain unclear.In this study, blood samples were collected from 11 members of a family with high prevalence of Parkinson's disease, including four affected cases, five suspected cases,and two non-affected cases.Point mutation screening of common mutation sites on PARK1 gene exon 4 was conducted using PCR, to determine the genetic loci of the causative gene for Parkinson's disease.Gene identification and sequencing results showed that a T base deletion mutation was observed in the PARK1 gene exon 4 of all 11 collected samples.It was confirmed that the PARKf gene exon 4 gene mutation is an important pathogenic mutation for Parkinson's disease.

  1. Autosomal dominant cyclic hematopoiesis: Genetics, phenotype, and natural history

    Energy Technology Data Exchange (ETDEWEB)

    Palmer, S.E.; Stephens, K.; Dale, D.C. [Univ. of Washington, Seattle, WA (United States)

    1994-09-01

    Autosomal dominant cyclic hematopoiesis (ADCH; cyclic neutropenia) is a rare disorder manifested by transient neutropenia that recurs every three weeks. To facilitate mapping the ADCH gene by genetic linkage analysis, we studied 9 ADCH families with 42 affected individuals. Pedigrees revealed AD inheritance with no evidence for decreased penetrance. Similar intra- and interfamilial variable expression was observed, with no evidence to support heterogeneity. At least 3 families displayed apparent new mutations. Many adults developed chronic neutropenia, while offspring always cycled during childhood. Children displayed recurrent oral ulcers, gingivitis, lymphadenopathy, fever, and skin and other infections with additional symptoms. Interestingly, there were no cases of neonatal infection. Some children required multiple hospitalizations for treatment. Four males under age 18 died of Clostridium sepsis following necrotizing enterocolitis; all had affected mothers. No other deaths due to ADCH were found; most had improvement of symptoms and infections as adults. Adults experienced increased tooth loss prior to age 30 (16 out of 27 adults, with 9 edentulous). No increase in myelodysplasia, malignancy, or congenital anomalies was observed. Recombinant G-CSF treatment resulted in dramatic improvement of symptoms and infections. The results suggest that ADCH is not a benign disorder, especially in childhood, and abdominal pain requires immediate evaluation. Diagnosis of ADCH requires serial blood counts in the proband and at least one CBC in relatives to exclude similar disorders. Genetic counseling requires specific histories as well as CBCs of each family member at risk to determine status regardless of symptom history, especially to assess apparent new mutations.

  2. An autosomal dominant syndrome of renal and anogenital malformations with syndactyly.

    Science.gov (United States)

    Green, A J; Sandford, R N; Davison, B C

    1996-07-01

    We describe a family with autosomal dominant inheritance of anal anomalies, renal tract abnormalities, genital malformations, and syndactyly. These clinical manifestations do not clearly fall into any previously described syndrome. A mother and daughter had almost identical congenital malformations, short stature, and unusual facies. The proband was born with anal stenosis, a rectovaginal fistula, clitoral hypertrophy, a pelvic right kidney, and syndactyly of both feet. Her daughter had the same anal, clitoral, and foot anomalies, a solitary pelvic kidney, and no fistula. This family is likely to represent autosomal dominant inheritance of a new combination of malformations, which may overlap with the Townes-Brocks syndrome, but does not fall into a current diagnostic category. PMID:8818947

  3. FAM83H Mutations in Families with Autosomal-Dominant Hypocalcified Amelogenesis Imperfecta

    OpenAIRE

    Kim, Jung-Wook; Lee, Sook-Kyung; Lee, Zang Hee; Park, Joo-Cheol; Lee, Kyung-Eun; Lee, Myoung-Hwa; Park, Jong-Tae; Seo, Byoung-Moo; Hu, Jan C.-C.; Simmer, James P.

    2008-01-01

    Amelogenesis imperfecta (AI) is a collection of diverse inherited disorders featuring dental-enamel defects in the absence of significant nondental symptoms. AI phenotypes vary and are categorized as hypoplastic, hypocalcified, and hypomaturation types. Phenotypic specificity to enamel has focused research on genes encoding enamel-matrix proteins. We studied two families with autosomal-dominant hypocalcified AI and have identified nonsense mutations (R325X and Q398X) in the FAM83H gene on chr...

  4. Spanish guidelines for the management of autosomal dominant polycystic kidney disease

    OpenAIRE

    E. Ars; Bernis, C.; Fraga, G.; Martínez, V.; Martins Muñoz, Judith Fátima; Ortiz, A.; Torra, R; Pérez, M. V.; Antón Pérez, G.; Furlano, M.; Ayasreh, N.

    2014-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent cause of genetic renal disease and accounts for 6-10% of patients on renal replacement therapy (RRT). Very few prospective, randomized trials or clinical studies address the diagnosis and management of this relatively frequent disorder. No clinical guidelines are available to date. This is a consensus statement presenting the recommendations of the Spanish Working Group on Inherited Kidney Diseases, which were agreed to...

  5. Recurrent Acute Pancreatitis and Cholangitis in a Patient with Autosomal Dominant Polycystic Kidney Disease

    OpenAIRE

    Kambiz Yazdanpanah; Navid Manouchehri; Elinaz Hosseinzadeh; Mohammad Hassan Emami; Mehdi Karami; Amir Hossein Sarrami

    2013-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder associated with multiple cyst formation in the different organs. Development of pancreatic cyst in ADPKD is often asymptomatic and is associated with no complication. A 38-year-old man with ADPKD was presented with six episodes of acute pancreatitis and two episodes of cholangitis in a period of 12 months. Various imaging studies revealed multiple renal, hepatic and pancreatic cysts, mild ectasia of pancreatic duct,...

  6. An autosomal dominant syndrome of renal and anogenital malformations with syndactyly.

    OpenAIRE

    Green, A.J.; Sandford, R. N.; Davison, B C

    1996-01-01

    We describe a family with autosomal dominant inheritance of anal anomalies, renal tract abnormalities, genital malformations, and syndactyly. These clinical manifestations do not clearly fall into any previously described syndrome. A mother and daughter had almost identical congenital malformations, short stature, and unusual facies. The proband was born with anal stenosis, a rectovaginal fistula, clitoral hypertrophy, a pelvic right kidney, and syndactyly of both feet. Her daughter had the s...

  7. A new mutation causing autosomal dominant periodic fever syndrome in a Danish family

    DEFF Research Database (Denmark)

    Weyhreter, Heike; Schwartz, Marianne; Kristensen, Tim D; Valerius, Niels Henrik; Pærregaard, Anders

    2003-01-01

    We describe four members in a family of 8 individuals over 3 generations with the autosomal dominant inherited periodic fever syndrome tumor necrosis factor receptor-associated periodic syndrome (TRAPS). The patients had recurrent episodes of fever, abdominal pain, arthritis, and rash. We examine...... to be healthy nor in 50 normal control patients. The youngest member of the family, a 2-year-old boy, was treated successfully with etanercept....

  8. Autosomal dominant rolandic epilepsy and speech dyspraxia: a new syndrome with anticipation.

    Science.gov (United States)

    Scheffer, I E; Jones, L; Pozzebon, M; Howell, R A; Saling, M M; Berkovic, S F

    1995-10-01

    We describe a family of 9 affected individuals in three generations with nocturnal oro-facio-brachial partial seizures, secondarily generalized partial seizures, and centro-temporal epileptiform discharges, associated with oral and speech dyspraxia and cognitive impairment. The speech disorder was prominent, but differed from that of Landau-Kleffner syndrome and of epilepsy with continuous spike and wave during slow-wave sleep. The electroclinical features of this new syndrome of autosomal dominant rolandic epilepsy resemble those of benign rolandic epilepsy, a common inherited epilepsy of childhood. This family shows clinical anticipation of the seizure disorder, the oral and speech dyspraxia, and cognitive dysfunction, suggesting that the genetic mechanism could be expansion of an unstable triplet repeat. Molecular studies on this syndrome, where the inheritance pattern is clear, could also be relevant to identifying a gene for benign rolandic epilepsy where anticipation does not occur and the mode of inheritance is uncertain. PMID:7574460

  9. Autosomal dominant arteriopathy with sub cortical infarcts and leucoencephalopathy (CADASIL)

    International Nuclear Information System (INIS)

    Cerebral autosomal dominant arteriopathy with sub cortical infarcts and leucoencephalopathy (CASADIL) is a systemic hereditary, vascular disease that involves small arteries. Recurrent ischemia, pseudo bulbar paralysis and dementia are characteristic. Other manifestations include migraine and depression. We report an Argentine family with VI generations with evidence of disease in IV. MR examinations were performed on 21 family members (both symptomatic and asymptomatic). The main findings on MR on symptomatic and asymptomatic patients were small lesions with high signal on T2 localised in periventricular white matter, brain stem, basal ganglia and thalamus, and confluent patches on white matter although with high signal on T2 images, usually symmetric. In conclusion we can assess that diffuse myelin loss and small infarcts occurring in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy well demonstrated with MR. In addition, some of the abnormalities in pre symptomatic patients can be identified on MR images. (author)

  10. CT in autosomal dominant and idiopathic cerebellar ataxia

    International Nuclear Information System (INIS)

    Signs of atrophy on cranial CT were investigated in 35 patients diagnosed as suffering from autosomal dominant (n=21) or idiopathic (n=14) cerebellar ataxia. Thirteen patients with a pure cerebellar syndrome were examined after at least 4 years of disease (mean duration 10.5 years) and were classified as cerebellar atrophy (CA). Twenty-two patients with additional non-cerebellar signs were classified as olivo-ponto-cerebellar atrophy (OPCA). Four (30%) of the patients with CA had atrophy of the brain stem in addition. Of the 22 patients with OPCA, 9 (40%) had atrophy of the cerebellum only. In patients with CA or OPCA correlation of clinical signs with severity of atrophy on CT was poor. Atrophy on CT often fails to differentiate autosomal dominant or idiopathic cerebellar ataxias in CA or OPCA: Patients with CA can also have atrophy of the brain stem and patients with OPCA do not necessarily show brain stem atrophy. (orig.)

  11. Urine proteome of autosomal dominant polycystic kidney disease patients

    OpenAIRE

    Bakun, Magda; Niemczyk, Mariusz; Domanski, Dominik; Jazwiec, Radek; Perzanowska, Anna; Niemczyk, Stanislaw; Kistowski, Michal; Fabijanska, Agnieszka; Borowiec, Agnieszka; Paczek, Leszek; Dadlez, Michal

    2012-01-01

    Background Autosomal dominant polycystic kidney disease (ADPKD) is responsible for 10% of cases of the end stage renal disease. Early diagnosis, especially of potential fast progressors would be of benefit for efficient planning of therapy. Urine excreted proteome has become a promising field of the search for marker patterns of renal diseases including ADPKD. Up to now however, only the low molecular weight fraction of ADPKD proteomic fingerprint was studied. The aim of our study was to char...

  12. Heterozygous Reelin Mutations Cause Autosomal-Dominant Lateral Temporal Epilepsy

    OpenAIRE

    Dazzo, Emanuela; Fanciulli, Manuela; Serioli, Elena; Minervini, Giovanni; Pulitano, Patrizia; Binelli, Simona; Di Bonaventura, Carlo; Luisi, Concetta; Pasini, Elena; Striano, Salvatore; Striano, Pasquale; Coppola, Giangennaro; Chiavegato, Angela; Radovic, Slobodanka; Spadotto, Alessandro

    2015-01-01

    Autosomal-dominant lateral temporal epilepsy (ADLTE) is a genetic epilepsy syndrome clinically characterized by focal seizures with prominent auditory symptoms. ADLTE is genetically heterogeneous, and mutations in LGI1 account for fewer than 50% of affected families. Here, we report the identification of causal mutations in reelin (RELN) in seven ADLTE-affected families without LGI1 mutations. We initially investigated 13 ADLTE-affected families by performing SNP-array linkage analysis and wh...

  13. Tolvaptan in patients with autosomal dominant polycystic kidney disease

    OpenAIRE

    Torres, Vicente E.; Chapman, Arlene B.; Devuyst, Olivier; Ron T Gansevoort; Grantham, Jared J.; Higashihara, Eiji; Perrone, Ronald D.; Krasa, Holly B.; Ouyang, John; Czerwiec, Frank S.

    2012-01-01

    BACKGROUND: The course of autosomal dominant polycystic kidney disease (ADPKD) is often associated with pain, hypertension, and kidney failure. Preclinical studies indicated that vasopressin V(2)-receptor antagonists inhibit cyst growth and slow the decline of kidney function. METHODS: In this phase 3, multicenter, double-blind, placebo-controlled, 3-year trial, we randomly assigned 1445 patients, 18 to 50 years of age, who had ADPKD with a total kidney volume of 750 ml or more and an estima...

  14. Sirolimus and kidney growth in autosomal dominant polycystic kidney disease

    OpenAIRE

    Serra, A. L.; Poster, D.; Kistler, A.D.; Krauer, F.; Raina, S; Young, J.; Rentsch, K M; Spanaus, K S; Senn, O; Kristanto, P; Scheffel, H.; Weishaupt, D; Wüthrich, R.P.

    2010-01-01

    BACKGROUND: In autosomal dominant polycystic kidney disease (ADPKD), aberrant activation of the mammalian target of rapamycin (mTOR) pathway is associated with progressive kidney enlargement. The drug sirolimus suppresses mTOR signaling. METHODS: In this 18-month, open-label, randomized, controlled trial, we sought to determine whether sirolimus halts the growth in kidney volume among patients with ADPKD. We randomly assigned 100 patients between the ages of 18 and 40 years to receive either ...

  15. Kidney volume and function in autosomal dominant polycystic kidney disease

    OpenAIRE

    Higashihara, Eiji; Nutahara, Kikuo; Okegawa, Takatsugu; Shishido, Toshihide; Tanbo, Mitsuhiro; Kobayasi, Kuninori; Nitadori, Toshiaki

    2013-01-01

    Background The significance of total kidney volume (TKV) as a biomarker of kidney function in autosomal dominant polycystic kidney disease (ADPKD) is controversial and has been reappraised. Methods Between 2007 and 2012, 64 patients were followed with a mean 39.7-month observation period. TKV measurements by magnetic resonance imaging and estimation of renal function with estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation and 24-h urine creati...

  16. Asymmetric crying facies with microcephaly and mental retardation. An autosomal dominant syndrome with variable expressivity.

    Science.gov (United States)

    Silengo, M C; Bell, G L; Biagioli, M; Guala, A; Bianco, R; Strandoni, P; De Sario, P N; Franceschini, P

    1986-12-01

    An infant boy with asymmetric crying facies, microcephaly, developmental retardation and failure to thrive is reported. His two siblings died in the newborn period because of complex congenital heart defects. The mother and the maternal grandmother have asymmetric crying facies, microcephaly and normal intelligence. A maternal aunt has severe physical and mental retardation, facial asymmetry, microcephaly, and cleft palate. This family allows an expansion of the spectrum of malformations associated with asymmetric crying facies and suggests autosomal dominant inheritance with variable expressivity. PMID:3815881

  17. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy with severe factor XII deficiency

    Directory of Open Access Journals (Sweden)

    Sternic Nadezda

    2009-12-01

    Full Text Available Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL is an inherited adult-onset microangiopathy caused by missense mutations in the Notch3gene on chromosome 19. However, common vascular risk factors may additionally modify clinical expression and progression of the disease. The role of various prothrombotic factors has also been implied. We report a case of a middle-aged man with typical clinical, neuroimaging and histological features of CADASIL, but with notably prolonged activated partial thromboplastin time. Hematological investigations revealed severe clotting Factor XII deficiency. This case illustrates that the occurrence of vascular risk factors should not be overlooked in patients with CADASIL.

  18. Dominantly inherited cleft lip and palate in two families.

    OpenAIRE

    Temple, K; Calvert, M; Plint, D; Thompson, E.; Pembrey, M

    1989-01-01

    Two families with non-syndromic cleft lip and cleft palate are described. The linear pattern of inheritance through several generations is difficult to explain by conventional multifactorial models. The pedigrees strengthen the suggestion that a dominantly inherited mutation exists with a major influence on clefting of the lip and palate alone.

  19. Autosomal dominant polycystic kidney disease: recent advances in clinical management.

    Science.gov (United States)

    Mao, Zhiguo; Chong, Jiehan; Ong, Albert C M

    2016-01-01

    The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD) go back at least 500 years to the late 16 (th) century. Advances in understanding disease presentation and pathophysiology have mirrored the progress of clinical medicine in anatomy, pathology, physiology, cell biology, and genetics. The identification of PKD1 and PKD2, the major genes mutated in ADPKD, has stimulated major advances, which in turn have led to the first approved drug for this disorder and a fresh reassessment of patient management in the 21 (st) century. In this commentary, we consider how clinical management is likely to change in the coming decade. PMID:27594986

  20. Autosomal dominant optic nerve colobomas, vesicoureteral reflux, and renal anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Schimmenti, L.A.; Pierpont, M.E.; Carpenter, B.L.M. [Univ. of Minnesota School of Medicine, MN (United States)] [and others

    1995-11-06

    We describe a father and 3 sons with optic nerve colobomas, vesicoureteral reflux, and renal anomalies. The youngest son had congenital renal failure and ultimately underwent renal transplantation. The father and one son had high frequency hearing loss. There were no other affected relatives. We conclude that the association of optic nerve colobomas, renal anomalies, and vesicoureteral reflux comprises a unique autosomal dominant syndrome. Molecular investigations have determined this disorder to be associated with a single nucleotide deletion in the PAX2 gene. 16 refs., 3 figs.

  1. The pathogenesis of autosomal dominant polycystic kidney disease: an update.

    Science.gov (United States)

    Somlo, S; Markowitz, G S

    2000-07-01

    The identification of PKD1 and PKD2, the two major genes responsible for autosomal dominant polycystic kidney disease, are the seminal discoveries upon which much of the current investigation into the pathogenesis of this common heritable disease is based. A major mechanistic insight was achieved with the discovery that autosomal dominant polycystic kidney disease occurs by a two-hit mechanism requiring somatic inactivation of the normal allele in individual polarized epithelial cells. Most recent advances are focused on the function of the respective protein products, polycystin-1 and polycystin-2. Indirect evidence supports an interaction between polycystin-1 and -2, albeit it is unlikely that they work in concert in all tissues and at all times. They associate in yeast two hybrid and cotransfection assays and there is a striking similarity in the renal and pancreatic cystic phenotypes of Pkd2-/- and Pkd1del34/del34 mice. Also, the respective homologues of both proteins are expressed in the same sensory neuronal cells in the nematode and the human disease phenotypes remain completely overlapping with the major difference being in relative severity. Mounting evidence supports the hypothesis that polycystin-1 is a cell surface receptor. A close homologue in the sea urchin sperm mediates the acrosome reaction in response to contact with egg-jelly, the nematode homologue functions in mechano- or chemosensation, and the solution structure of the repeated extracellular polycystic kidney disease domains reveals a beta-sandwich fold commonly found in surface receptor molecules. Indirect evidence also supports the initial hypothesis that polycystin-2 is a calcium channel subunit. Several closely related homologues retain the calcium channel signature motif but differ in their predicted interaction domains, and one of these homologues has been shown to be a calcium regulated cation channel. Several important distinctions in polcystin-1 and -2 function have also been

  2. LAMB3 mutations causing autosomal-dominant amelogenesis imperfecta.

    Science.gov (United States)

    Kim, J W; Seymen, F; Lee, K E; Ko, J; Yildirim, M; Tuna, E B; Gencay, K; Shin, T J; Kyun, H K; Simmer, J P; Hu, J C-C

    2013-10-01

    Amelogenesis imperfecta (AI) can be either isolated or part of a larger syndrome. Junctional epidermolysis bullosa (JEB) is a collection of autosomal-recessive disorders featuring AI associated with skin fragility and other symptoms. JEB is a recessive syndrome usually caused by mutations in both alleles of COL17A1, LAMA3, LAMB3, or LAMC2. In rare cases, heterozygous carriers in JEB kindreds display enamel malformations in the absence of skin fragility (isolated AI). We recruited two kindreds with autosomal-dominant amelogenesis imperfecta (ADAI) characterized by generalized severe enamel hypoplasia with deep linear grooves and pits. Whole-exome sequencing of both probands identified novel heterozygous mutations in the last exon of LAMB3 that likely truncated the protein. The mutations perfectly segregated with the enamel defects in both families. In Family 1, an 8-bp deletion (c.3446_3453del GACTGGAG) shifted the reading frame (p.Gly 1149Glufs*8). In Family 2, a single nucleotide substitution (c.C3431A) generated an in-frame translation termination codon (p.Ser1144*). We conclude that enamel formation is particularly sensitive to defects in hemidesmosome/basement-membrane complexes and that syndromic and non-syndromic forms of AI can be etiologically related. PMID:23958762

  3. [The dominant inheritance of periodic catatonia].

    Science.gov (United States)

    von Trostorff, S

    1981-03-01

    In 143 patients suffering from periodic catatonia we found the disease in a direct succession five times in four generations and 17 times in three generations. With direct succession in four generations we found in two cases manifest psychosis in all generations, in three generations one member was formed by a most severely abnormal personality. In the sequence of three generations, the psychosis occurred continuously in ten families, in seven cases an abnormal personality pointed to the disease by his peculiarities. Since the occurrence of psychic diseases and abnormalities in the family is frequently concealed, the cases found are of great importance and indicate a dominant hereditary course. This assumption is substantiated by number of diseased half-brothers and sisters. Cataphasia in several generations in a direct sequence is a rarer phenomenon. Besides periodic catatonia, it showed the greatest affliction among the various forms of schizophrenia. PMID:7244040

  4. Autism in siblings with autosomal dominant nocturnal frontal lobe epilepsy.

    Science.gov (United States)

    Miyajima, Tomoko; Kumada, Tomohiro; Saito, Keiko; Fujii, Tatsuya

    2013-02-01

    In 1999, Hirose et al. reported a Japanese family with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) associated with a neuronal nicotinic acetylcholine receptor α4 subunit mutation (S252L). We followed the siblings of this family, and found that the elder brother had Asperger's disorder without mental retardation (MR) and the younger brother had autistic disorder with profound MR. The clinical epileptic features of the siblings were very similar, and both had deficits in socialization, but their cognitive development differed markedly. It thus seems that epilepsy is the direct phenotype of the S252L mutation, whereas other various factors modulate the cognitive and social development. No patients with ADNFLE have previously been reported to have autism spectrum disorder or profound MR. PMID:22883468

  5. Mutationsanalyse an 14 Kandidatengenen für autosomal-dominant vererbte arrhythmogene rechtsventrikuläre Kardiomyopathie (ARVD5)

    OpenAIRE

    Brandt, Kalina

    2011-01-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of the right ventricular free wall and leads to ventricular arrhythmias, heart failure, and sudden cardiac death. Genetics gains in importance due to the possibility of preventing sudden death by implantation of a cardioverter defibrillator (ICD) in asymptomatic patients with familial history of ARVC. The aim of this thesis was to identify the mutation for autosomal dominant inherited ARVD5 o...

  6. Therapeutic mTOR Inhibition in Autosomal Dominant Polycystic Kidney Disease: What Is the Appropriate Serum Level?

    OpenAIRE

    Canaud, G; Knebelmann, B.; Harris, P. C.; Vrtovsnik, F; Correas, J. M.; Pallet, N; Heyer, C. M.; Letavernier, E.; Bienaimé, F.; Thervet, E; Martinez, F; Terzi, F.; Legendre, C.

    2010-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease, and sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been shown to significantly retard cyst expansion in animal models. The optimal therapeutic dose of sirolimus is not yet defined. Here, we report the history of a previously unknown ADPKD deceased donor whose kidneys were engrafted in two different recipients. One of the two received an immunosuppressive regimen based on sirolimu...

  7. Renal and extrarenal manifestations of autosomal dominant polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    E.A. Romão

    2006-04-01

    Full Text Available The objective of the present study was to determine the frequency of the most common clinical features in patients with autosomal dominant polycystic kidney disease in a sample of the Brazilian population. The medical records of 92 patients with autosomal dominant polycystic kidney disease attended during the period from 1985 to 2003 were reviewed. The following data were recorded: age at diagnosis, gender, associated clinical manifestations, occurrence of stroke, age at loss of renal function (beginning of dialysis, and presence of a family history. The involvement of abdominal viscera was investigated by ultrasonography. Intracranial alterations were prospectively investigated by magnetic resonance angiography in 42 asymptomatic patients, and complemented with digital subtraction arteriography when indicated. Mean age at diagnosis was 35.1 ± 14.9 years, and mean serum creatinine at referral was 2.4 ± 2.8 mg/dL. The most frequent clinical manifestations during the disease were arterial hypertension (63.3%, lumbar pain (55.4%, an abdominal mass (47.8%, and urinary infection (35.8%. Loss of renal function occurred in 27 patients (mean age: 45.4 ± 9.5 years. The liver was the second organ most frequently affected (39.1%. Stroke occurred in 7.6% of the patients. Asymptomatic intracranial aneurysm was detected in 3 patients and arachnoid cysts in 3 other patients. In conclusion, the most common clinical features were lumbar pain, arterial hypertension, abdominal mass, and urinary infection, and the most serious complications were chronic renal failure and stroke. Both intracranial aneurysms and arachnoid cysts occurred in asymptomatic patients at a frequency of 7.14%.

  8. Autosomal dominant polycystic kidney disease: genetics, epidemiology, and treatment

    Directory of Open Access Journals (Sweden)

    Reed-Gitomer B

    2014-10-01

    Full Text Available Berenice Reed-Gitomer Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA Abstract: Autosomal dominant polycystic kidney disease (ADPKD is the most common potentially lethal genetic disorder, accounting for 2%–8% of end-stage renal disease worldwide. While development of renal cysts is the major characteristic of ADPKD, several disease-related complications contribute significantly to morbidity and mortality. Since introduction of renal replacement therapies, cardiovascular disease is the leading cause of death among ADPKD patients. Loss of renal function requiring renal replacement therapy occurs in 50% of patients by the age of 60 years. The results of recent large epidemiological studies in ADPKD have shown little progress in delaying onset of renal failure despite an improvement in patient mortality. Significant progress has been made over the past decade in elucidating the genetics of the disorder. Genetic testing is now available in most countries, and development of more reliable methods for prenatal diagnosis of ADPKD has increased the sensitivity of testing. While there are no approved drugs for treatment of ADPKD within the USA, the first agent targeting renal disease progression in this disorder was recently approved for clinical use in Japan. Furthermore, several additional drugs for treatment of ADPKD are currently under clinical investigation. Overall, this presents an optimistic future for new therapeutic interventions in this disease. This paper reviews the current knowledge related to the epidemiology, genetics, and treatment of ADPKD. Keywords: autosomal dominant polycystic kidney disease, hereditary renal disease, renal cyst, genetics

  9. Recurrent acute pancreatitis and cholangitis in a patient with autosomal dominant polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    Kambiz Yazdanpanah

    2013-01-01

    Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is an inherited disorder associated with multiple cyst formation in the different organs. Development of pancreatic cyst in ADPKD is often asymptomatic and is associated with no complication. A 38-year-old man with ADPKD was presented with six episodes of acute pancreatitis and two episodes of cholangitis in a period of 12 months. Various imaging studies revealed multiple renal, hepatic and pancreatic cysts, mild ectasia of pancreatic duct, dilation of biliary system and absence of biliary stone. He was managed with conservative treatment for each attack. ADPKD should be considered as a potential risk factor for recurrent acute and/or chronic pancreatitis and cholangitis.

  10. [Clinical diagnosis of Autosomal Dominant Polycystic Kidney Disease].

    Science.gov (United States)

    Magistroni, Riccardo; Izzi, Claudia; Scolari, Francesco

    2016-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder related to kidney. ADPKD is usually easy to diagnose in people who have a family history of ADPKDs developing typical symptoms, including flank, abdominal pain or macroscopic hematuria. In this setting, diagnosis in adults at risk for ADPKD is commonly performed by ultrasonography, which reveals two enlarged kidneys with multiple bilateral cysts. ADPKD may be more difficult to diagnose in the absence of family history or in subjects with atypical presentation, including asymmetric or focal renal imaging findings, discordant disease within family, early onset of ADPKD and development of ESRD before 30 yr of age. The presence of a total of three or more renal cysts for at-risk subjects aged 15-39 years and two cysts or more in each kidney for at-risk subjects aged 40-59 years are sufficient for the diagnosis of ADPKD. The absence of any renal cyst is sufficient for disease exclusion only for at-risk subjects aged 40 years or older. If the family history is negative, the diagnosis of ADPKD can be made in a patient with enlarged kidneys, numerous cysts, presence of liver cysts and absence of findings suggesting a different cystic disease. If the imaging diagnosis is not clear or showing atypical manifestations in subjects, molecular genetic testing should be performed. PMID:27067212

  11. Patterns of autosomal dominant polycystic kidney diseases in black Africans

    Directory of Open Access Journals (Sweden)

    Fary Ka Elhadj

    2010-01-01

    Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is not well described in black Africans while some data suggesting the disease is exceptional in this race. A retrospective study of patients with ADPKD followed in nephrology department of a teaching hospital in Dakar (January 1, 1995 to December 31, 2005 was therefore undertaken. Prevalence of ADPKD was one in 250. Mean age was 47 ± 5 years with a predominance of male (57%. High blood pressure (HBP was present in 68% of patients. Other renal manifestations were flank pain, hematuria and proteinuria. Majority of patients had impaired renal function at time of diagnosis. Extra-renal cysts were essentially found in liver (45.5%, pancreas and seminal vesicles. Main complications: ESRD (51% occurred within a 6 year mean period, urinary tract infection (13% and cerebral haemorrhage (2%. HBP control, in general needed 2 or more antihypertensive drugs. Fourteen patients died, ten patients had been on haemodialysis and four others died from uremic compli-cations. In conclusion, ADPKD in black African adults is not rare and probably underdiagnosed. Early HBP and ESRD are likely more frequent than in other races. Earlier ultrasound detection and strategies to preserve renal function should be offered to at-risk individuals to improve outcomes.

  12. Caffeine intake by patients with autosomal dominant polycystic kidney disease

    Energy Technology Data Exchange (ETDEWEB)

    Vendramini, L.C.; Nishiura, J.L.; Baxmann, A.C.; Heilberg, I.P. [Disciplina de Nefrologia, Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil)

    2012-07-20

    Because caffeine may induce cyst and kidney enlargement in autosomal dominant polycystic kidney disease (ADPKD), we evaluated caffeine intake and renal volume using renal ultrasound in ADPKD patients. Caffeine intake was estimated by the average of 24-h dietary recalls obtained on 3 nonconsecutive days in 102 ADPKD patients (68 females, 34 males; 39 ± 12 years) and compared to that of 102 healthy volunteers (74 females, 28 males; 38 ± 14 years). The awareness of the need for caffeine restriction was assessed. Clinical and laboratory data were obtained from the medical records of the patients. Mean caffeine intake was significantly lower in ADPKD patients versus controls (86 vs 134 mg/day), and 63% of the ADPKD patients had been previously aware of caffeine restriction. Caffeine intake did not correlate with renal volume in ADPKD patients. There were no significant differences between the renal volumes of patients in the highest and lowest tertiles of caffeine consumption. Finally, age-adjusted multiple linear regression revealed that renal volume was associated with hypertension, chronic kidney disease stage 3 and the time since diagnosis, but not with caffeine intake. The present small cross-sectional study indicated a low level of caffeine consumption by ADPKD patients when compared to healthy volunteers, which was most likely due to prior awareness of the need for caffeine restriction. Within the range of caffeine intake observed by ADPKD patients in this study (0-471 mg/day), the renal volume was not directly associated with caffeine intake.

  13. Caffeine intake by patients with autosomal dominant polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    L.C. Vendramini

    2012-09-01

    Full Text Available Because caffeine may induce cyst and kidney enlargement in autosomal dominant polycystic kidney disease (ADPKD, we evaluated caffeine intake and renal volume using renal ultrasound in ADPKD patients. Caffeine intake was estimated by the average of 24-h dietary recalls obtained on 3 nonconsecutive days in 102 ADPKD patients (68 females, 34 males; 39 ± 12 years and compared to that of 102 healthy volunteers (74 females, 28 males; 38 ± 14 years. The awareness of the need for caffeine restriction was assessed. Clinical and laboratory data were obtained from the medical records of the patients. Mean caffeine intake was significantly lower in ADPKD patients versus controls (86 vs 134 mg/day, and 63% of the ADPKD patients had been previously aware of caffeine restriction. Caffeine intake did not correlate with renal volume in ADPKD patients. There were no significant differences between the renal volumes of patients in the highest and lowest tertiles of caffeine consumption. Finally, age-adjusted multiple linear regression revealed that renal volume was associated with hypertension, chronic kidney disease stage 3 and the time since diagnosis, but not with caffeine intake. The present small cross-sectional study indicated a low level of caffeine consumption by ADPKD patients when compared to healthy volunteers, which was most likely due to prior awareness of the need for caffeine restriction. Within the range of caffeine intake observed by ADPKD patients in this study (0-471 mg/day, the renal volume was not directly associated with caffeine intake.

  14. Why kidneys fail in autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Grantham, Jared J; Mulamalla, Sumanth; Swenson-Fields, Katherine I

    2011-10-01

    The weight of evidence gathered from studies in humans with hereditary polycystic kidney disease (PKD)1 and PKD2 disorders, as well as from experimental animal models, indicates that cysts are primarily responsible for the decline in glomerular filtration rate that occurs fairly late in the course of the disease. The processes underlying this decline include anatomic disruption of glomerular filtration and urinary concentration mechanisms on a massive scale, coupled with compression and obstruction by cysts of adjacent nephrons in the cortex, medulla and papilla. Cysts prevent the drainage of urine from upstream tributaries, which leads to tubule atrophy and loss of functioning kidney parenchyma by mechanisms similar to those found in ureteral obstruction. Cyst-derived chemokines, cytokines and growth factors result in a progression to fibrosis that is comparable with the development of other progressive end-stage renal diseases. Treatment of renal cystic disorders early enough to prevent or reduce cyst formation or slow cyst growth, before the secondary changes become widespread, is a reasonable strategy to prolong the useful function of kidneys in patients with autosomal dominant polycystic kidney disease. PMID:21862990

  15. Imaging for the prognosis of autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Bae, Kyongtae T; Grantham, Jared J

    2010-02-01

    Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the unrelenting enlargement of innumerable cysts derived from renal tubules. This cystic growth often leads to a grotesque renal enlargement. Relatively early in life, the cysts trigger secondary complications including pain, hypertension and gross hematuria; renal insufficiency is usually not detected until the fifth or sixth decade of life. Therapies targeted to molecular and pathophysiological abnormalities slow cyst growth and protect renal function in animal models of the disease. Unfortunately, the translation of these treatments into clinical trials is hampered since glomerular filtration rate, the usual biomarker of renal disease progression, does not decrease substantially until extensive and irreversible damage to noncystic parenchyma occurs. Ultrasonography, CT and MRI have been used for many years to quantify the increase in renal volume in patients with ADPKD. Imaging with these techniques has also been used to accurately quantify the rate of increased kidney and total cyst volume in patients. In this Review we discuss the overwhelming evidence in support of the view that imaging is an invaluable tool to monitor the onset and progression of ADPKD and is well-suited to gauge the response of this disease to targeted therapy before renal function begins to decline. PMID:20111050

  16. Reproductive issues for adults with autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Vora, Neeta; Perrone, Ronald; Bianchi, Diana W

    2008-02-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a common disorder. However, the consequences of ADPKD on male and female reproductive health are not widely known. Several abnormalities are found in men with ADPKD, including necrospermia, immotile sperm, seminal vesicle cysts, and ejaculatory duct cysts. Female fertility is not affected. Affected women with ADPKD and normal renal function have a high rate of successful uncomplicated pregnancies. Pregnant women with ADPKD with compromised kidney function should be monitored carefully for the development of hypertension and preeclampsia. Their fetuses should be examined sonographically for signs of uteroplacental insufficiency, such as intrauterine growth restriction and oligohydramnios. The diagnosis of ADPKD should always be considered when prenatal sonographic findings of hyperechogenic enlarged kidneys are found. In this setting, a family history and renal sonogram of both parents is indicated. Sequencing of the PKD1 and PKD2 genes is available and can be used for both prenatal and preimplantation genetic diagnosis. We review in detail these topics to familiarize physicians taking care of patients with ADPKD with the reproductive issues that confront affected individuals. PMID:18215709

  17. Evaluation of Nephrolithiasis in Autosomal Dominant Polycystic Kidney Disease Patients

    Science.gov (United States)

    Nishiura, José L.; Neves, Rodrigo F.C.A.; Eloi, Samara R.M.; Cintra, Susan M.L.F.; Ajzen, Sergio A.; Heilberg, Ita P.

    2009-01-01

    Background and objectives: Nephrolithiasis (LIT) is more prevalent in patients with autosomal dominant polycystic kidney disease (ADPKD) than in the general population. Renal ultrasonography may underdetect renal stones because of difficulties imposed by parenchymal and/or cyst wall calcifications. Design, setting, participants, & measurements: A total of 125 patients with ADPKD underwent ultrasonography and unenhanced computed tomography (CT) scan, routine blood chemistry, and spot and 24-h urine collections. Results: CT scan detected calculi in 32 patients, including 20 whose previous ultrasonography revealed no calculi. The percentage of hypocitraturia was high but not statistically different between patients with ADPKD+LIT or ADPKD. Hyperuricosuria and distal renal tubular acidosis were less prevalent but also did not differ between groups, whereas hyperoxaluria was significantly higher in the former. Hypercalciuria was not detected. Renal volume was significantly higher in patients with ADPKD+LIT versus ADPKD, and a stepwise multivariate logistic regression analysis showed that a renal volume ≥500 ml was a significant predictor of LIT in patients with ADPKD and normal renal function, after adjustments for age and hypertension. Conclusions: CT scan was better than ultrasonography to detect LIT in patients with ADPKD. Larger kidneys from patients with ADPKD were more prone to develop stones, irrespective of the presence of metabolic disturbances. PMID:19339428

  18. Autosomal dominant Parkinson's disease caused by SNCA duplications.

    Science.gov (United States)

    Konno, Takuya; Ross, Owen A; Puschmann, Andreas; Dickson, Dennis W; Wszolek, Zbigniew K

    2016-01-01

    The discovery in 1997 that mutations in the SNCA gene cause Parkinson's disease (PD) greatly advanced our understanding of this illness. There are pathogenic missense mutations and multiplication mutations in SNCA. Thus, not only a mutant protein, but also an increased dose of wild-type protein can produce autosomal dominant parkinsonism. We review the literature on SNCA duplications and focus on pathologically-confirmed cases. We also report a newly-identified American family with SNCA duplication whose proband was autopsied. We found that over half of the reported cases with SNCA duplication had early-onset parkinsonism and non-motor features, such as dysautonomia, rapid eye movement sleep behavior disorder (RBD), hallucinations (usually visual) and cognitive deficits leading to dementia. Only a few cases have presented with typical features of PD. Our case presented with depression and RBD that preceded parkinsonism, and dysautonomia that led to an initial diagnosis of multiple system atrophy. Dementia and visual hallucinations followed. Our patient and the other reported cases with SNCA duplications had widespread cortical Lewy pathology. Neuronal loss in the hippocampal cornu ammonis 2/3 regions were seen in about half of the autopsied SNCA duplication cases. Similar pathology was also observed in SNCA missense mutation and triplication carriers. PMID:26350119

  19. Research on autosomal dominant polycystic kidney disease in China

    Institute of Scientific and Technical Information of China (English)

    DAI Bing; MEI Chang-lin

    2006-01-01

    Objective To review the history and recent development of research on autosomal dominant polycystic kidney disease (ADPKD) in China.Data sources Both Chinese and English literatures were searched in MEDLINE/CD ROM (1979 - 2006) and the Chinese Biomedical Literature Disk (1979 - 2006).Study selection Published articles about ADPKD from mainland of China were selected. Data were mainly extracted from 58 articles which are listed in the reference section of this review.Results Some preliminary reports on cyst decompression surgeries and mutation analysis represent the contribution to the ADPKD research from China in the history. A serial of basic research and clinical studies on ADPKD in recent years also have been summarized. A technique platform for ADPKD research was firstly established. The genomics/proteomics/bioinformatics approach was introduced, which provide a lot of valuable information for understanding the pathogenesis. By denature high performance liquid chromatography (DHPLC)technique the entire PKD1 and PKD2 gene sequence screening system for Chinese Han population has been successfully established. Based on the characteristic data of Chinese patients, an integrated therapy protocol was put forward and won an advantage over the traditional therapy. Some novel experimental studies on therapy also were encouraging. Conclusions Remarkable progress of ADPKD research in China have been made recently. Still many works, including the government support, international collaboration and active participation of more Chinese nephrologists, should be enhanced to advance this process in the near future.

  20. Evidence for locus heterogeneity in human autosomal dominant split hand/split foot malformation

    Energy Technology Data Exchange (ETDEWEB)

    Evans, J.P.; Palmer, S.E.; Wijsman, E.M. [Univ. of Washington, Seattle, WA (United States)] [and others

    1994-09-01

    Split hand/split foot (SHSF, also known as ectrodactyly) is a human developmental disorder characterized by absent central rays and other distal limb malformations. Physical mapping of SHSF-associated chromosomal rearrangements has provided compelling evidence for the location of a causative gene locus (designated SHFD1) on chromosome 7 within q21.3-q22.1. In the present study, marker loci were localized to the SHFD1 critical region through the analysis of somatic cell hybrids derived from individuals with SHSF and cytogenetic abnormalities involving the 7q21.3q22.1 region. Combined genetic and physical data suggest that the order of markers in the SHFD1 critical region is cen - D7S492 - COL1A2 - D7S527 - D7S479 - D7S491 - SHFD1 - D7S554 - ASNS - D7S518 -qter. Dinucleotide repeat polymorphisms at several of these loci were used to test for linkage of SHSF to this region in a large pedigree that demonstrated autosomal dominant inheritance of this disorder. Strong evidence against linkage of SHSF to the SHFD1 critical region was obtained, and the gene responsible for the SHSF phenotype in this pedigree was excluded from a 10 cM interval spanning the entire SHFD1 critical region. Evidence of exclusion to the SHFD1 critical region was also observed in five additional families. Thus, combined molecular and genetic data provide evidence for locus heterogeneity in autosomal dominant SHSF, implying that mutations in at least two separate autosomal genes can result in this distinctive human developmental disorder.

  1. Molecular and cellular pathogenesis of autosomal dominant polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    A.P. Bastos

    2011-07-01

    Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is one of the most common human life-threatening monogenic disorders. The disease is characterized by bilateral, progressive renal cystogenesis and cyst and kidney enlargement, often leading to end-stage renal disease, and may include extrarenal manifestations. ADPKD is caused by mutation in one of two genes, PKD1 and PKD2, which encode polycystin-1 (PC1 and polycystin-2 (PC2, respectively. PC2 is a non-selective cation channel permeable to Ca2+, while PC1 is thought to function as a membrane receptor. The cyst cell phenotype includes increased proliferation and apoptosis, dedifferentiation, defective planar polarity, and a secretory pattern associated with extracellular matrix remodeling. The two-hit model for cyst formation has been recently extended by the demonstration that early gene inactivation leads to rapid and diffuse development of renal cysts, while inactivation in adult life is followed by focal and late cyst formation. Renal ischemia/reperfusion, however, can function as a third hit, triggering rapid cyst development in kidneys with Pkd1 inactivation induced in adult life. The PC1-PC2 complex behaves as a sensor in the primary cilium, mediating signal transduction via Ca2+ signaling. The intracellular Ca2+ homeostasis is impaired in ADPKD, being apparently responsible for the cAMP accumulation and abnormal cell proliferative response to cAMP. Activated mammalian target for rapamycin (mTOR and cell cycle dysregulation are also significant features of PKD. Based on the identification of pathways altered in PKD, a large number of preclinical studies have been performed and are underway, providing a basis for clinical trials in ADPKD and helping the design of future trials.

  2. Heterozygous Reelin Mutations Cause Autosomal-Dominant Lateral Temporal Epilepsy

    Science.gov (United States)

    Dazzo, Emanuela; Fanciulli, Manuela; Serioli, Elena; Minervini, Giovanni; Pulitano, Patrizia; Binelli, Simona; Di Bonaventura, Carlo; Luisi, Concetta; Pasini, Elena; Striano, Salvatore; Striano, Pasquale; Coppola, Giangennaro; Chiavegato, Angela; Radovic, Slobodanka; Spadotto, Alessandro; Uzzau, Sergio; La Neve, Angela; Giallonardo, Anna Teresa; Mecarelli, Oriano; Tosatto, Silvio C.E.; Ottman, Ruth; Michelucci, Roberto; Nobile, Carlo

    2015-01-01

    Autosomal-dominant lateral temporal epilepsy (ADLTE) is a genetic epilepsy syndrome clinically characterized by focal seizures with prominent auditory symptoms. ADLTE is genetically heterogeneous, and mutations in LGI1 account for fewer than 50% of affected families. Here, we report the identification of causal mutations in reelin (RELN) in seven ADLTE-affected families without LGI1 mutations. We initially investigated 13 ADLTE-affected families by performing SNP-array linkage analysis and whole-exome sequencing and identified three heterozygous missense mutations co-segregating with the syndrome. Subsequent analysis of 15 small ADLTE-affected families revealed four additional missense mutations. 3D modeling predicted that all mutations have structural effects on protein-domain folding. Overall, RELN mutations occurred in 7/40 (17.5%) ADLTE-affected families. RELN encodes a secreted protein, Reelin, which has important functions in both the developing and adult brain and is also found in the blood serum. We show that ADLTE-related mutations significantly decrease serum levels of Reelin, suggesting an inhibitory effect of mutations on protein secretion. We also show that Reelin and LGI1 co-localize in a subset of rat brain neurons, supporting an involvement of both proteins in a common molecular pathway underlying ADLTE. Homozygous RELN mutations are known to cause lissencephaly with cerebellar hypoplasia. Our findings extend the spectrum of neurological disorders associated with RELN mutations and establish a link between RELN and LGI1, which play key regulatory roles in both the developing and adult brain. PMID:26046367

  3. Heterozygous reelin mutations cause autosomal-dominant lateral temporal epilepsy.

    Science.gov (United States)

    Dazzo, Emanuela; Fanciulli, Manuela; Serioli, Elena; Minervini, Giovanni; Pulitano, Patrizia; Binelli, Simona; Di Bonaventura, Carlo; Luisi, Concetta; Pasini, Elena; Striano, Salvatore; Striano, Pasquale; Coppola, Giangennaro; Chiavegato, Angela; Radovic, Slobodanka; Spadotto, Alessandro; Uzzau, Sergio; La Neve, Angela; Giallonardo, Anna Teresa; Mecarelli, Oriano; Tosatto, Silvio C E; Ottman, Ruth; Michelucci, Roberto; Nobile, Carlo

    2015-06-01

    Autosomal-dominant lateral temporal epilepsy (ADLTE) is a genetic epilepsy syndrome clinically characterized by focal seizures with prominent auditory symptoms. ADLTE is genetically heterogeneous, and mutations in LGI1 account for fewer than 50% of affected families. Here, we report the identification of causal mutations in reelin (RELN) in seven ADLTE-affected families without LGI1 mutations. We initially investigated 13 ADLTE-affected families by performing SNP-array linkage analysis and whole-exome sequencing and identified three heterozygous missense mutations co-segregating with the syndrome. Subsequent analysis of 15 small ADLTE-affected families revealed four additional missense mutations. 3D modeling predicted that all mutations have structural effects on protein-domain folding. Overall, RELN mutations occurred in 7/40 (17.5%) ADLTE-affected families. RELN encodes a secreted protein, Reelin, which has important functions in both the developing and adult brain and is also found in the blood serum. We show that ADLTE-related mutations significantly decrease serum levels of Reelin, suggesting an inhibitory effect of mutations on protein secretion. We also show that Reelin and LGI1 co-localize in a subset of rat brain neurons, supporting an involvement of both proteins in a common molecular pathway underlying ADLTE. Homozygous RELN mutations are known to cause lissencephaly with cerebellar hypoplasia. Our findings extend the spectrum of neurological disorders associated with RELN mutations and establish a link between RELN and LGI1, which play key regulatory roles in both the developing and adult brain. PMID:26046367

  4. Aicardi syndrome associated with autosomal genomic imbalance: coincidence or evidence for autosomal inheritance with sex-limited expression?

    Science.gov (United States)

    Prontera, P; Bartocci, A; Ottaviani, V; Isidori, I; Rogaia, D; Ardisia, C; Guercini, G; Mencarelli, A; Donti, E

    2013-04-01

    Aicardi syndrome (AIS), a rare neurodevelopmental disorder thought to be caused by an X-linked dominant mutation, is characterized by 3 main features: agenesis of corpus callosum, infantile spams and chorioretinal lacunae. A genome-wide study of a girl with AIS lead us to identify a 6q deletion;12q duplication, derived from a maternal 6q;12q translocation. The two intellectually impaired brothers of the proband showed the same genomic anomalies, but not the constellation of features characterizing the AIS. This could be either a coincidental observation of 2 rare conditions, but can also suggest an alternative hypothesis for the genetic etiology of AIS, indicating the existence of a subset of autosomal genes whose mutation could act in a sex-confined manner. PMID:23801936

  5. Quantitative Amyloid Imaging in Autosomal Dominant Alzheimer's Disease: Results from the DIAN Study Group.

    Directory of Open Access Journals (Sweden)

    Yi Su

    Full Text Available Amyloid imaging plays an important role in the research and diagnosis of dementing disorders. Substantial variation in quantitative methods to measure brain amyloid burden exists in the field. The aim of this work is to investigate the impact of methodological variations to the quantification of amyloid burden using data from the Dominantly Inherited Alzheimer's Network (DIAN, an autosomal dominant Alzheimer's disease population. Cross-sectional and longitudinal [11C]-Pittsburgh Compound B (PiB PET imaging data from the DIAN study were analyzed. Four candidate reference regions were investigated for estimation of brain amyloid burden. A regional spread function based technique was also investigated for the correction of partial volume effects. Cerebellar cortex, brain-stem, and white matter regions all had stable tracer retention during the course of disease. Partial volume correction consistently improves sensitivity to group differences and longitudinal changes over time. White matter referencing improved statistical power in the detecting longitudinal changes in relative tracer retention; however, the reason for this improvement is unclear and requires further investigation. Full dynamic acquisition and kinetic modeling improved statistical power although it may add cost and time. Several technical variations to amyloid burden quantification were examined in this study. Partial volume correction emerged as the strategy that most consistently improved statistical power for the detection of both longitudinal changes and across-group differences. For the autosomal dominant Alzheimer's disease population with PiB imaging, utilizing brainstem as a reference region with partial volume correction may be optimal for current interventional trials. Further investigation of technical issues in quantitative amyloid imaging in different study populations using different amyloid imaging tracers is warranted.

  6. Genetics Home Reference: autosomal dominant nocturnal frontal lobe epilepsy

    Science.gov (United States)

    ... and wander around, which can be mistaken for sleepwalking. The person may also cry out or make ... occur? How can gene mutations affect health and development? More about Mutations and Health Inheritance Pattern This ...

  7. Ser217Cys mutation in the Ig Ⅱ domain of FGFR3 in a Chinese family with autosomal dominant achondroplasia

    Institute of Scientific and Technical Information of China (English)

    ZHANG Shi-rong; ZHOU Xiao-qing; REN Xiang; WANG Tian-tian; YUAN Ming-xiong; WANG Qing; LIU Jing-yu; LIU Mu-gen

    2007-01-01

    @@ Achondroplasia (ACH) is the most common form of skeletal dysplasia characterized by disproportionately short stature, lumbar lordosis, relative macrocephaly and other skeletal anomalies resulting from a defect in the maturation of the chondrocytes in the growth plate of the cartilage. The combined frequency of the disease has been estimated to be 1 in 15 000 live births.1 ACH is inherited in autosomal dominant fashion with a complete penetrance, more than 80% of affected individuals have de novo mutations associated with increased paternal age.

  8. A Case of New Familiar Genetic Variant of Autosomal Dominant Polycystic Kidney Disease-2: A Case Study

    OpenAIRE

    Litvinchuk, Tetiana; Tao, Yunxia; Singh, Ruchi; Tetyana L. Vasylyeva

    2015-01-01

    Background Autosomal dominant polycystic kidney disease (ADPKD) is characterized by renal cyst formation due to mutations in genes coding for polycystin-1 [PKD1 (85–90% of cases), on ch 16p13.3] and polycystin-2 [PKD2 (10–15% of cases), on ch 4q13-23] and PKD3 gene (gene unmapped). It is also associated with TSC2/PKD1 contiguous gene syndrome. ADPKD is usually inherited, but new mutations without a family history occur in approximately 10% of the cases. Case presentation A 17-year-...

  9. In Vivo CRISPR/Cas9 Gene Editing Corrects Retinal Dystrophy in the S334ter-3 Rat Model of Autosomal Dominant Retinitis Pigmentosa

    OpenAIRE

    Bakondi, Benjamin; Lv, Wenjian; Lu, Bin; Jones, Melissa K.; Tsai, Yuchun; Kim, Kevin J; Levy, Rachelle; Akhtar, Aslam Abbasi; Breunig, Joshua J.; Svendsen, Clive N.; Wang, Shaomei

    2016-01-01

    Reliable genome editing via Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 may provide a means to correct inherited diseases in patients. As proof of principle, we show that CRISPR/Cas9 can be used in vivo to selectively ablate the rhodopsin gene carrying the dominant S334ter mutation (Rho S334) in rats that model severe autosomal dominant retinitis pigmentosa. A single subretinal injection of guide RNA/Cas9 plasmid in combination with electroporation generated allele-...

  10. Imaging of the Macula Indicates Early Completion of Structural Deficit in Autosomal-Dominant Optic Atrophy

    DEFF Research Database (Denmark)

    Rönnbäck, Cecilia; Milea, Dan; Larsen, Michael

    2013-01-01

    Optical coherence tomography (OCT) enables 3-dimensional imaging of the retina, including the layer of ganglion cells that supplies the optic nerve with its axons. We tested OCT as means of diagnosing and phenotyping autosomal-dominant optic atrophy (ADOA)....

  11. Molecular diagnosis of autosomal dominant early onset Alzheimer's disease: an update

    OpenAIRE

    Raux, G; Guyant-Marechal, L; Martin, C.; BOU, J.; Penet, C; Brice, A; Hannequin, D.; Frebourg, T; Campion, D

    2005-01-01

    Background: Autosomal dominant early onset Alzheimer's disease (ADEOAD) is genetically heterogeneous. Mutations of the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes have been identified.

  12. Molecular Diagnostics in Autosomal Dominant Polycystic Kidney Disease: Utility and Limitations

    OpenAIRE

    Zhao, Xiao; Paterson, Andrew D.; Zahirieh, Alireza; He, Ning; Wang, Kairong; Pei, York

    2008-01-01

    Background and objectives: Gene-based mutation screening is now available and has the potential to provide diagnostic confirmation or exclusion of autosomal dominant polycystic kidney disease. This study illustrates its utility and limitations in the clinical setting.

  13. Genetics Home Reference: cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

    Science.gov (United States)

    Skip to main content Your Guide to Understanding Genetic Conditions Enable Javascript for addthis links to activate. ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions CADASIL cerebral autosomal dominant arteriopathy ...

  14. An 11-Year-Old Child with Autosomal Dominant Polycystic Kidney Disease Who Presented with Nephrolithiasis

    Directory of Open Access Journals (Sweden)

    Fatih Firinci

    2012-01-01

    Full Text Available Patients with autosomal dominant polycystic kidney disease become symptomatic and are diagnosed usually at adulthood. The rate of nephrolithiasis in these patients is 5–10 times the rate in the general population, and both anatomic and metabolic abnormalities play role in the formation of renal stones. However, nephrolithiasis is rare in childhood age group. In this paper, an 11-year-old child with autosomal dominant polycystic kidney disease presenting with nephrolithiasis is discussed.

  15. Gene expression in early and progression phases of autosomal dominant polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    Tzeng Yi-Shiuan

    2008-12-01

    Full Text Available Abstract Background Little is known about the genes involved in the initial cyst formation and disease progression in autosomal dominant polycystic kidney disease (ADPKD; however, such knowledge is necessary to explore therapeutic avenues for this common inherited kidney disease. Findings To uncover the genetic determinants and molecular mechanisms of ADPKD, we analyzed 4-point time-series DNA microarrays from Pkd1L3/L3 mice to generate high resolution gene expression profiles at different stages of disease progression. We found different characteristic gene expression signatures in the kidneys of Pkd1L3/L3 mice compared to age-matched controls during the initial phase of the disease. By postnatal week 1, the Pkd1L3/L3 kidney already had a distinctive gene expression pattern different from the corresponding normal controls. Conclusion The genes differentially expressed, either induced or repressed, in ADPKD are important in immune defense, cell structure and motility, cellular proliferation, apoptosis and metabolic processes, and include members of three pathways (Wnt, Notch, and BMP involved in morphogenetic signaling. Further analysis of the gene expression profiles from the early stage of cystogenesis to end stage disease identified a possible gene network involved in the pathogenesis of ADPKD.

  16. Characterization of a novel autosomal dominant bleeding disorder in a large kindred from east Texas.

    Science.gov (United States)

    Kuang, S Q; Hasham, S; Phillips, M D; Wolf, D; Wan, Y; Thiagarajan, P; Milewicz, D M

    2001-03-15

    A large east Texas family with autosomal dominant inheritance of a novel bleeding disorder has been identified. The disorder is characterized clinically by easy bruising, life-threatening bleeding with trauma or surgery, and menorrhagia in affected women. Laboratory studies demonstrated prolongation of the prothrombin time and activated partial thromboplastin time in affected individuals. Paradoxically, assays of known coagulation factors are all within normal limits. To determine the molecular basis of this disease, a candidate gene linkage analysis in this kindred was done. Initially it was hypothesized that the cause of the disease in this family could be an antithrombin III (AT3) mutation that resulted in a constitutively active AT3 in the absence of heparin binding. Linkage studies using DNA from the family and an intragenic polymorphic marker within the AT3 gene showed that the disease mapped to this locus. The coding region and intron/exon junctions of AT3 were sequenced using the proband's DNA, but this analysis failed to identify a mutation. Additional family members were recruited for the study, and 16 polymorphic markers around the AT3 gene were analyzed. Using 2 recombinants, the critical interval for the defective gene was narrowed to approximately 1.5 Mb, centromeric to AT3. The factor V (FV) gene was mapped into the disease interval and sequenced; there were no mutations found. Elucidation of the genetic defect causing the bleeding disorder in this family may reveal a novel protein involved in the coagulation cascade. PMID:11238089

  17. Sex-linked dominant

    Science.gov (United States)

    Inheritance - sex-linked dominant; Genetics - sex-linked dominant; X-linked dominant; Y-linked dominant ... type of chromosome that is affected (autosomal or sex chromosome). It also depends on whether the trait ...

  18. Sex-linked dominant

    Science.gov (United States)

    Inheritance - sex-linked dominant; Genetics - sex-linked dominant; X-linked dominant; Y-linked dominant ... can be either an autosomal chromosome or a sex chromosome. It also depends on whether the trait ...

  19. A novel missense mutation in the CLCN7 gene linked to benign autosomal dominant osteopetrosis: a case series

    Directory of Open Access Journals (Sweden)

    Rashid Ban Mousa

    2013-01-01

    Full Text Available Abstract Introduction Osteopetrosis is a rare inherited genetic disease characterized by sclerosis of the skeleton. The absence or malfunction of osteoclasts is found to be strongly associated with the disease evolution. Currently, four clinically distinct forms of the disease have been recognized: the infantile autosomal recessive osteopetrosis, the malignant and the intermediate forms, and autosomal dominant osteopetrosis, type I and type II forms. The autosomal recessive types are the most severe forms with symptoms in very early childhood, whereas the autosomal dominant classes exhibit a heterogeneous trait with milder symptoms, often at later childhood or adulthood. Case presentation Case 1 is the 12-year-old daughter (index patient of an Iraqi-Kurdish family who, at the age of eight years, was diagnosed clinically to have mild autosomal dominant osteopetrosis. Presently, at 12-years old, she has severe complications due to the disease progression. In addition, the same family previously experienced the death of a female child in her late childhood. The deceased child had been misdiagnosed, at that time, with thalassemia major. In this report, we extended our investigation to identify the type of the inheritance patterns of osteopetrosis using molecular techniques, because consanguineous marriages exist within the family history. We have detected one heterozygous mutation in exon 15 of the Chloride Channel 7 gene in the index patient (Case 1, whereas other mutations were not detected in the associated genes TCIRG1, OSTM1, RANK, and RANKL. The missense mutation (CGG>TGG located in exon 15 (c.1225C>T of the Chloride Channel 7 gene changed the amino acid position 409 from arginine to tryptophan (p.R409W, c.1225C>T. Case 2 is the 16-year-old son (brother of the index patient of the same family who was diagnosed clinically with mild autosomal dominant osteopetrosis. We have identified the same heterozygous mutation in exon 15 of the Chloride

  20. Fibrosis and progression of autosomal dominant polycystic kidney disease (ADPKD).

    Science.gov (United States)

    Norman, Jill

    2011-10-01

    The age on onset of decline in renal function and end-stage renal disease (ESRD) in autosomal polycystic kidney disease (ADPKD) is highly variable and there are currently no prognostic tools to identify patients who will progress rapidly to ESRD. In ADPKD, expansion of cysts and loss of renal function are associated with progressive fibrosis. Similar to the correlation between tubulointerstitial fibrosis and progression of chronic kidney disease (CKD), in ADPKD, fibrosis has been identified as the most significant manifestation associated with an increased rate of progression to ESRD. Fibrosis in CKD has been studied extensively. In contrast, little is known about the mechanisms underlying progressive scarring in ADPKD although some commonality may be anticipated. Current data suggest that fibrosis associated with ADPKD shares at least some of the "classical" features of fibrosis in CKD (increased interstitial collagens, changes in matrix metalloproteinases (MMPs), over-expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), over-expression of plasminogen activator inhibitor-1 (PAI-1) and increased transforming growth factor beta (TGFβ) but that there are also some unique and stage-specific features. Epithelial changes appear to precede and to drive interstitial changes leading to the proposal that development of fibrosis in ADPKD is biphasic with alterations in cystic epithelia precipitating changes in interstitial fibroblasts and that reciprocal interactions between these cell types drives progressive accumulation of extracellular matrix (ECM). Since fibrosis is a major component of ADPKD it follows that preventing or slowing fibrosis should retard disease progression with obvious therapeutic benefits. The development of effective anti-fibrotic strategies in ADPKD is dependent on understanding the precise mechanisms underlying initiation and progression of fibrosis in ADPKD and the role of the intrinsic genetic defect in these processes. This article is

  1. Mitochondriales Maltargeting eines peroxisomalen Proteins als Ursache eines autosomal-dominant vererbten renalen Fanconi-Syndroms

    OpenAIRE

    Peindl, Dominika Elisabeth

    2012-01-01

    Das renale Fanconi-Syndrom beschreibt generell eine Funktionsstörung des proximalen Nierentubulus mit charakteristischen Symptomen wie Glukosurie, Aminoazidurie und Proteinurie. Klinisch kommt es bei den Patienten zu Rachitis, metabolischer Azidose, Elektrolytstörungen und Dehydratation. Die Erkrankung kann autosomal-dominant, autosomal-rezessiv oder x-chromosomal auftreten, wobei auch mitochondriale Funktionsstörungen in der Pathogenese eine wichtige Rolle spielen, da der proximale Tubulus i...

  2. Autosomal dominant cerebellar ataxia type I: A review of the phenotypic and genotypic characteristics

    Directory of Open Access Journals (Sweden)

    Fujioka Shinsuke

    2011-05-01

    examination, genetic molecular testing, and exclusion of other diseases. Differential diagnosis is broad and includes secondary ataxias caused by drug or toxic effects, nutritional deficiencies, endocrinopathies, infections and post-infection states, structural abnormalities, paraneoplastic conditions and certain neurodegenerative disorders. Given the autosomal dominant pattern of inheritance, genetic counseling is essential and best performed in specialized genetic clinics. There are currently no known effective treatments to modify disease progression. Care is therefore supportive. Occupational and physical therapy for gait dysfunction and speech therapy for dysarthria is essential. Prognosis is variable depending on the type of ADCA and even among kindreds.

  3. Autosomal dominant pseudohypoaldosteronism type 1 with a novel splice site mutation in MR gene

    Directory of Open Access Journals (Sweden)

    Kaito Hiroshi

    2009-11-01

    Full Text Available Abstract Background Autosomal dominant pseudohypoaldosteronism type 1 (PHA1 is a rare inherited condition that is characterized by renal resistance to aldosterone as well as salt wasting, hyperkalemia, and metabolic acidosis. Renal PHA1 is caused by mutations of the human mineralcorticoid receptor gene (MR, but it is a matter of debate whether MR mutations cause mineralcorticoid resistance via haploinsufficiency or dominant negative mechanism. It was previously reported that in a case with nonsense mutation the mutant mRNA was absent in lymphocytes because of nonsense mediated mRNA decay (NMD and therefore postulated that haploinsufficiency alone can give rise to the PHA1 phenotype in patients with truncated mutations. Methods and Results We conducted genomic DNA analysis and mRNA analysis for familial PHA1 patients extracted from lymphocytes and urinary sediments and could detect one novel splice site mutation which leads to exon skipping and frame shift result in premature termination at the transcript level. The mRNA analysis showed evidence of wild type and exon-skipped RT-PCR products. Conclusion mRNA analysis have been rarely conducted for PHA1 because kidney tissues are unavailable for this disease. However, we conducted RT-PCR analysis using mRNA extracted from urinary sediments. We could demonstrate that NMD does not fully function in kidney cells and that haploinsufficiency due to NMD with premature termination is not sufficient to give rise to the PHA1 phenotype at least in this mutation of our patient. Additional studies including mRNA analysis will be needed to identify the exact mechanism of the phenotype of PHA.

  4. Anesthetic Management and Postoperative Care of a Patient with CADASIL (Cerebral Arteriopathy, Autosomal Dominant, with Subcortical Infarcts and leukoencephalopathy) for Cesarean Section

    OpenAIRE

    Sousan Rasooli; Farnaz Moslemi; Simin Tagavi

    2014-01-01

    CADASIL (cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy) is an infrequent inherited small artery disease that could have anesthetic implications. However these have rarely been reported. We present an anesthetic experience of a female patient previously diagnosed with CADASIL, who had suffered an ischemic vascular cerebral accident with a MRI compatible with leukoencephalopathy, and who was dependent for daily activities, mood alterations, apathy,...

  5. A new novel mutation in FBN1 causes autosomal dominant Marfan syndrome in a Chinese family

    OpenAIRE

    Dong, Jiamei; Bu, Juan; Du, Wei; Li, Yuan; Jia, Yanlei; Li, Jianchang; Meng, Xiaoli; Minghui YUAN; Peng, Xiaojuan; Zhou, Aimin; Wang, Lejin

    2012-01-01

    Purpose Screening of mutations in the fibrillin-1 (FBN1) gene in a Chinese family with autosomal dominant Marfan syndrome (MFS). Methods It has been reported that FBN1 mutations account for approximately 90% of Autosomal Dominant MFS. FBN1 mutations were analyzed in a Chinese family of 36 members including 13 MFS patients. The genomic DNAs from blood leukocytes of the patients and their relatives were isolated and the entire coding region of FBN1 was amplified by PCR. The sequence of FBN1 was...

  6. Identification of novel mutations in Chinese Hans with autosomal dominant polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    Yu Chaowen

    2011-12-01

    Full Text Available Abstract Background Autosomal dominant polycystic kidney disease (ADPKD is the most common inherited renal disease with an incidence of 1 in 400 to 1000. The disease is genetically heterogeneous, with two genes identified: PKD1 (16p13.3 and PKD2 (4q21. Molecular diagnosis of the disease in at-risk individuals is complicated due to the structural complexity of PKD1 gene and the high diversity of the mutations. This study is the first systematic ADPKD mutation analysis of both PKD1 and PKD2 genes in Chinese patients using denaturing high-performance liquid chromatography (DHPLC. Methods Both PKD1 and PKD2 genes were mutation screened in each proband from 65 families using DHPLC followed by DNA sequencing. Novel variations found in the probands were checked in their family members available and 100 unrelated normal controls. Then the pathogenic potential of the variations of unknown significance was examined by evolutionary comparison, effects of amino acid substitutions on protein structure, and effects of splice site alterations using online mutation prediction resources. Results A total of 92 variations were identified, including 27 reported previously. Definitely pathogenic mutations (ten frameshift, ten nonsense, two splicing defects and one duplication were identified in 28 families, and probably pathogenic mutations were found in an additional six families, giving a total detection level of 52.3% (34/65. About 69% (20/29 of the mutations are first reported with a recurrent mutation rate of 31%. Conclusions Mutation study of PKD1 and PKD2 genes in Chinese Hans with ADPKD may contribute to a better understanding of the genetic diversity between different ethnic groups and enrich the mutation database. Besides, evaluating the pathogenic potential of novel variations should also facilitate the clinical diagnosis and genetic counseling of the disease.

  7. Allele-specific gene silencing in two mouse models of autosomal dominant skeletal myopathy.

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    Ryan E Loy

    Full Text Available We explored the potential of mutant allele-specific gene silencing (ASGS in providing therapeutic benefit in two established mouse models of the autosomal dominantly-inherited muscle disorders, Malignant Hyperthermia (MH and Central Core Disease (CCD. Candidate ASGS siRNAs were designed and validated for efficacy and specificity on ryanodine receptor (RyR1 cDNA mini-constructs expressed in HEK293 cells using RT-PCR- and confocal microscopy-based assays. In vivo delivery of the most efficacious identified siRNAs into flexor digitorum brevis (FDB muscles was achieved by injection/electroporation of footpads of 4-6 month old heterozygous Ryr1(Y524S/+ (YS/+ and Ryr1(I4895T/+ (IT/+ knock-in mice, established mouse models of MH with cores and CCD, respectively. Treatment of IT/+ mice resulted in a modest rescue of deficits in the maximum rate (∼38% rescue and magnitude (∼78% of ligand-induced Ca(2+ release that occurred in the absence of a change in the magnitude of electrically-evoked Ca(2+ release. Compared to the difference between the caffeine sensitivity of Ca(2+ release in FDB fibers from YS/+ and WT mice treated with SCR siRNA (EC(50: 1.1 mM versus 4.4 mM, respectively, caffeine sensitivity was normalized in FDB fibers from YS/+ mice following 2 (EC(50: 2.8 mM and 4 week (EC(50: 6.6 mM treatment with YS allele-specific siRNA. Moreover, the temperature-dependent increase in resting Ca(2+ observed in FDB fibers from YS/+ mice was normalized to WT levels after 2 weeks of treatment with YS allele-specific siRNA. As determined by quantitative real time PCR, the degree of functional rescue in YS/+ and IT/+ mice correlated well with the relative increase in fractional WT allele expression.

  8. A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy.

    Science.gov (United States)

    Vissing, John; Barresi, Rita; Witting, Nanna; Van Ghelue, Marijke; Gammelgaard, Lise; Bindoff, Laurence A; Straub, Volker; Lochmüller, Hanns; Hudson, Judith; Wahl, Christoph M; Arnardottir, Snjolaug; Dahlbom, Kathe; Jonsrud, Christoffer; Duno, Morten

    2016-08-01

    Limb girdle muscular dystrophy type 2A is the most common limb girdle muscular dystrophy form worldwide. Although strict recessive inheritance is assumed, patients carrying a single mutation in the calpain 3 gene (CAPN3) are reported. Such findings are commonly attributed to incomplete mutation screening. In this investigation, we report 37 individuals (age range: 21-85 years, 21 females and 16 males) from 10 families in whom only one mutation in CAPN3 could be identified; a 21-bp, in-frame deletion (c.643_663del21). This mutation co-segregated with evidence of muscle disease and autosomal dominant transmission in several generations. Evidence of muscle disease was indicated by muscle pain, muscle weakness and wasting, significant fat replacement of muscles on imaging, myopathic changes on muscle biopsy and loss of calpain 3 protein on western blotting. Thirty-one of 34 patients had elevated creatine kinase or myoglobin. Muscle weakness was generally milder than observed in limb girdle muscular dystrophy type 2A, but affected the same muscle groups (proximal leg, lumbar paraspinal and medial gastrocnemius muscles). In some cases, the weakness was severely disabling. The 21-bp deletion did not affect mRNA maturation. Calpain 3 expression in muscle, assessed by western blot, was below 15% of normal levels in the nine mutation carriers in whom this could be tested. Haplotype analysis in four families from three different countries suggests that the 21-bp deletion is a founder mutation. This study provides strong evidence that heterozygosity for the c.643_663del21 deletion in CAPN3 results in a dominantly inherited muscle disease. The normal expression of mutated mRNA and the severe loss of calpain 3 on western blotting, suggest a dominant negative effect with a loss-of-function mechanism affecting the calpain 3 homodimer. This renders patients deficient in calpain 3 as in limb girdle muscular dystrophy type 2A, albeit in a milder form in most cases. Based on findings

  9. DGAT2 Mutation in a Family with Autosomal-Dominant Early-Onset Axonal Charcot-Marie-Tooth Disease.

    Science.gov (United States)

    Hong, Young Bin; Kang, Junghee; Kim, Ji Hyun; Lee, Jinho; Kwak, Geon; Hyun, Young Se; Nam, Soo Hyun; Hong, Hyun Dae; Choi, Yu-Ri; Jung, Sung-Chul; Koo, Heasoo; Lee, Ji Eun; Choi, Byung-Ok; Chung, Ki Wha

    2016-05-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy and is a genetically and clinically heterogeneous disorder. We examined a Korean family in which two individuals had an autosomal-dominant axonal CMT with early-onset, sensory ataxia, tremor, and slow disease progression. Pedigree analysis and exome sequencing identified a de novo missense mutation (p.Y223H) in the diacylglycerol O-acyltransferase 2 (DGAT2) gene. DGAT2 encodes an endoplasmic reticulum-mitochondrial-associated membrane protein, acyl-CoA:diacylglycerol acyltransferase, which catalyzes the final step of the triglyceride (TG) biosynthesis pathway. The patient showed consistently decreased serum TG levels, and overexpression of the mutant DGAT2 significantly inhibited the proliferation of mouse motor neuron cells. Moreover, the variant form of human DGAT2 inhibited the axonal branching in the peripheral nervous system of zebrafish. We suggest that mutation of DGAT2 is the novel underlying cause of an autosomal-dominant axonal CMT2 neuropathy. This study will help provide a better understanding of the pathophysiology of axonal CMT and contribute to the molecular diagnostics of peripheral neuropathies. PMID:26786738

  10. Fasting in a 16-year-old girl at-risk of autosomal dominant polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    Faezeh Sadeghi

    2015-05-01

    Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is the most common form of inherited kidney disease that results in renal failure. PKD currently has no causative therapy. However, some treatment options are available, ranging from symptomatic therapy to delaying the onset of end-stage renal failure. Early diagnosis of adult polycystic kidney disease is vital in order to prevent its complications. Ultrasonongraphy and genetic testing are the two preferred diagnostic techniques with defined limitations, mainly regarding age. Herein, we report a case of an ADPKD family whom visited the genetic counseling clinic for determining the disease risk in their symptom-free girls aged 16 and 22 years, and discussing other related issues such as their concern about fasting in Ramadan.

  11. Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum.

    OpenAIRE

    Campion, D; Dumanchin, C; Hannequin, D.; Dubois, B.; Belliard, S; Puel, M; Thomas-Anterion, C.; Michon, A.; Martin, C.; Charbonnier, F; Raux, G; Camuzat, A; Penet, C; Mesnage, V; Martinez, M.

    1999-01-01

    To determine the prevalence of early-onset Alzheimer disease (EOAD) and of autosomal dominant forms of EOAD (ADEOAD), we performed a population-based study in the city of Rouen (426,710 residents). EOAD was defined as onset of disease at age

  12. Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy

    NARCIS (Netherlands)

    Ostergaard, P.; Simpson, M.A.; Mendola, A.; Vasudevan, P.; Connell, F.C.; van Impel, A.; Moore, A.T.; Loeys, B.L.; Ghalamkarpour, A.; Onoufriadis, A.; Martinez-Corral, I.; Devery, S.; Leroy, J.G.; van Laer, L.; Singer, A.; Bialer, M.G.; McEntagart, M.; Quarrell, O.; Brice, G.; Trembath, R.C.; Schulte-Merker, S.; Makinen, T.; Vikkula, M.; Mortimer, P.S.; Mansour, S.; Jeffery, S.

    2012-01-01

    We have identified KIF11 mutations in individuals with syndromic autosomal-dominant microcephaly associated with lymphedema and/or chorioretinopathy. Initial whole-exome sequencing revealed heterozygous KIF11 mutations in three individuals with a combination of microcephaly and lymphedema from a mic

  13. Autopsy Report with Clinical and Pathophysiologic Discussion of Autosomal Dominant Adult Polycystic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Anup Hazra

    2014-01-01

    Full Text Available The average weight of a kidney is approximately 135 gm, measuring on average 10 × 6 × 4 cm. In hereditary conditions, autosomal dominant and autosomal recessive polycystic kidney disease, the shape, size, and the weight can be significantly abnormal, causing progressive renal failure, often necessitating dialysis or renal transplant for survival. We report a case of adult polycystic kidney disease in a 50-year-old female without a family history, who died of complications of the disease which included accelerated hypertension, and renal and cardiac failure.

  14. In Vivo CRISPR/Cas9 Gene Editing Corrects Retinal Dystrophy in the S334ter-3 Rat Model of Autosomal Dominant Retinitis Pigmentosa

    Science.gov (United States)

    Bakondi, Benjamin; Lv, Wenjian; Lu, Bin; Jones, Melissa K; Tsai, Yuchun; Kim, Kevin J; Levy, Rachelle; Akhtar, Aslam Abbasi; Breunig, Joshua J; Svendsen, Clive N; Wang, Shaomei

    2016-01-01

    Reliable genome editing via Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 may provide a means to correct inherited diseases in patients. As proof of principle, we show that CRISPR/Cas9 can be used in vivo to selectively ablate the rhodopsin gene carrying the dominant S334ter mutation (RhoS334) in rats that model severe autosomal dominant retinitis pigmentosa. A single subretinal injection of guide RNA/Cas9 plasmid in combination with electroporation generated allele-specific disruption of RhoS334, which prevented retinal degeneration and improved visual function. PMID:26666451

  15. In Vivo CRISPR/Cas9 Gene Editing Corrects Retinal Dystrophy in the S334ter-3 Rat Model of Autosomal Dominant Retinitis Pigmentosa.

    Science.gov (United States)

    Bakondi, Benjamin; Lv, Wenjian; Lu, Bin; Jones, Melissa K; Tsai, Yuchun; Kim, Kevin J; Levy, Rachelle; Akhtar, Aslam Abbasi; Breunig, Joshua J; Svendsen, Clive N; Wang, Shaomei

    2016-03-01

    Reliable genome editing via Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 may provide a means to correct inherited diseases in patients. As proof of principle, we show that CRISPR/Cas9 can be used in vivo to selectively ablate the rhodopsin gene carrying the dominant S334ter mutation (Rho(S334)) in rats that model severe autosomal dominant retinitis pigmentosa. A single subretinal injection of guide RNA/Cas9 plasmid in combination with electroporation generated allele-specific disruption of Rho(S334), which prevented retinal degeneration and improved visual function. PMID:26666451

  16. Mutations in BICD2, which encodes a golgin and important motor adaptor, cause congenital autosomal-dominant spinal muscular atrophy.

    Science.gov (United States)

    Neveling, Kornelia; Martinez-Carrera, Lilian A; Hölker, Irmgard; Heister, Angelien; Verrips, Aad; Hosseini-Barkooie, Seyyed Mohsen; Gilissen, Christian; Vermeer, Sascha; Pennings, Maartje; Meijer, Rowdy; te Riele, Margot; Frijns, Catharina J M; Suchowersky, Oksana; MacLaren, Linda; Rudnik-Schöneborn, Sabine; Sinke, Richard J; Zerres, Klaus; Lowry, R Brian; Lemmink, Henny H; Garbes, Lutz; Veltman, Joris A; Schelhaas, Helenius J; Scheffer, Hans; Wirth, Brunhilde

    2013-06-01

    Spinal muscular atrophy (SMA) is a heterogeneous group of neuromuscular disorders caused by degeneration of lower motor neurons. Although functional loss of SMN1 is associated with autosomal-recessive childhood SMA, the genetic cause for most families affected by dominantly inherited SMA is unknown. Here, we identified pathogenic variants in bicaudal D homolog 2 (Drosophila) (BICD2) in three families afflicted with autosomal-dominant SMA. Affected individuals displayed congenital slowly progressive muscle weakness mainly of the lower limbs and congenital contractures. In a large Dutch family, linkage analysis identified a 9q22.3 locus in which exome sequencing uncovered c.320C>T (p.Ser107Leu) in BICD2. Sequencing of 23 additional families affected by dominant SMA led to the identification of pathogenic variants in one family from Canada (c.2108C>T [p.Thr703Met]) and one from the Netherlands (c.563A>C [p.Asn188Thr]). BICD2 is a golgin and motor-adaptor protein involved in Golgi dynamics and vesicular and mRNA transport. Transient transfection of HeLa cells with all three mutant BICD2 cDNAs caused massive Golgi fragmentation. This observation was even more prominent in primary fibroblasts from an individual harboring c.2108C>T (p.Thr703Met) (affecting the C-terminal coiled-coil domain) and slightly less evident in individuals with c.563A>C (p.Asn188Thr) (affecting the N-terminal coiled-coil domain). Furthermore, BICD2 levels were reduced in affected individuals and trapped within the fragmented Golgi. Previous studies have shown that Drosophila mutant BicD causes reduced larvae locomotion by impaired clathrin-mediated synaptic endocytosis in neuromuscular junctions. These data emphasize the relevance of BICD2 in synaptic-vesicle recycling and support the conclusion that BICD2 mutations cause congenital slowly progressive dominant SMA. PMID:23664116

  17. Aicardi Syndrome Associated with Autosomal Genomic Imbalance: Coincidence or Evidence for Autosomal Inheritance with Sex-Limited Expression?

    OpenAIRE

    Prontera, P; Bartocci, A; Ottaviani, V.; Isidori, I.; Rogaia, D; Ardisia, C.; Guercini, G.; Mencarelli, A; Donti, E.

    2013-01-01

    Aicardi syndrome (AIS), a rare neurodevelopmental disorder thought to be caused by an X-linked dominant mutation, is characterized by 3 main features: agenesis of corpus callosum, infantile spams and chorioretinal lacunae. A genome-wide study of a girl with AIS lead us to identify a 6q deletion;12q duplication, derived from a maternal 6q;12q translocation. The two intellectually impaired brothers of the proband showed the same genomic anomalies, but not the constellation of features character...

  18. Autosomal Dominant Polycystic Kidney Disease Patient Specified Bilateral Renal Mass: A Case Report

    Directory of Open Access Journals (Sweden)

    Ercan Ogreden

    2014-12-01

    Full Text Available Hereditary cystic lesions of the kidney cysts nonherediter lesion with a wide range. They may be the only finding in the form of extrarenal renal cysts may also be part of a clinical syndrome. For this reason, multi-disciplinary approach brings with cystic lesions in the different units. Autosomal dominant polycystic kidney disease, kidney different sizes and numbers of both systemic and hereditary disease that manifests itself in the form of cystic changes. Hereditary and acquired cystic lesions on the basis of some of the rare tumor association is determined in several studies. Here are diagnosed with autosomal dominant polycystic kidney disease, abdominal pain because of a mass in the last six months, physical examination, radiological and laboratory findings were diagnosed with bilateral renal tumors are uncommon and the right renal mass nephron-sparing surgery, the patients with left renal mass followed with active surveillance discussed in the current literature.

  19. Autosomal dominant ataxia: Genetic evidence for locus heterogeneity from a cuban founder-effect population

    OpenAIRE

    Auburger, Georg; Diaz, Guillermo Orozco; Capote, Raul Ferreira; Sanchez, Suzana Gispert; Perez, Marta Paradoa; del Cueto, Marianela Estrada; Meneses, Mirna Garcia; Farrall, Martin; Williamson, Robert; Chamberlain, Susan; Baute, Luis Heredero

    1990-01-01

    The locus for autosomal dominant ataxia with a diagnosis of olivo-ponto-cerebellar atrophy at autopsy has been previously assigned to chromosome 6p. However, evidence for two alternative locations has been reported. We have recently described a large potential founder-effect population of such patients in the Holguin province of Cuba. With an estimated 1,000 patients available for analysis, this extensive cluster of families provides a unique opportunity for the definitive localization of the...

  20. Successful conservative treatment of bilateral emphysematous pyelonephritis in autosomal dominant polycystic kidney disease

    OpenAIRE

    Jaisuresh, K.; Bavaharan, R.

    2013-01-01

    Emphysematous pyelonephritis is a rare, potentially lethal complication of polycystic kidney disease. Treatment mostly includes emergency nephrectomy of the affected kidney. We report a case of bilateral emphysematous pyelonephritis in a 57-year-old diabetic male with autosomal dominant polycystic kidney disease, who recovered with conservative treatment. Escherichia coli was cultured from the cyst aspirate. He was treated with percutaneous needle aspiration of infected cysts and intravenous ...

  1. Autosomal dominant cortical tremor, myoclonus, and epilepsy (ADCME: Probable first family from India

    Directory of Open Access Journals (Sweden)

    Chandra Mohan Sharma

    2014-01-01

    Full Text Available Autosomal dominant cortical tremor, myoclonus, and epilepsy (ADCME is an extremely rare syndrome characterized by familial occurrence of postural and action-induced tremors of the hands but showing electrophysiologic findings of cortical reflex myoclonus. Patients also have cognitive decline and tonic-clonic seizures, often precipitated by sleep deprivation or photic stimulation. We describe probably the first family from India of this ill-defined syndrome.

  2. CHRNB2 Is the Second Acetylcholine Receptor Subunit Associated with Autosomal Dominant Nocturnal Frontal Lobe Epilepsy*

    OpenAIRE

    Phillips, Hilary A.; Favre, Isabelle; Kirkpatrick, Martin; Zuberi, Sameer M; Goudie, David; Heron, Sarah E.; Scheffer, Ingrid E.; Sutherland, Grant R.; Berkovic, Samuel F; Bertrand, Daniel; Mulley, John C

    2000-01-01

    Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is an uncommon, idiopathic partial epilepsy characterized by clusters of motor seizures occurring in sleep. We describe a mutation of the β2 subunit of the nicotinic acetylcholine receptor, effecting a V287M substitution within the M2 domain. The mutation, in an evolutionary conserved region of CHRNB2, is associated with ADNFLE in a Scottish family. Functional receptors with the V287M mutation are highly expressed in Xenopus oocytes ...

  3. Determinants of renal volume in autosomal-dominant polycystic kidney disease

    OpenAIRE

    Grantham, JJ; Cook, LT; Torres, VE; Bost, JE; Chapman, AB; Harris, PC; Guay-Woodford, LM; Bae, KT

    2007-01-01

    The Consortium of Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) recently showed that renal enlargement in autosomal-dominant polycystic kidney disease mimicked exponential growth. We determined the effects of cyst initiation rate, total number, and growth rate on the time-dependent change of total cyst volume (TCV). Mathematical models with equations integrating cyst surface area, volume, and an invariant growth rate constant were used to compute the time-dependent change in...

  4. Autosomal dominant polycystic kidney disease: new treatment options and how to test their efficacy

    OpenAIRE

    Wüthrich, R.P.; Serra, A. L.; Kistler, A.D.

    2009-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) represents a slowly progressing cystic kidney disorder which evolves into end-stage renal disease in the majority of patients. Currently, there are no established treatments to retard the progression of the disease, but several promising therapeutic options are being tested in ongoing clinical trials. An inherent dilemma for the investigation of therapies in ADPKD is the dissociation of the early onset and constant rate of cyst growth from ...

  5. Laparoscopic biopsy-proven lupus nephritis in autosomal dominant polycystic kidney disease

    OpenAIRE

    Park, Ji In; Lee, Hajeong; An, Jung Nam; Chin, Ho Jun; Kim, Suhnggwon

    2012-01-01

    A 48-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) presented with generalized edema and arthralgia. She showed evidences of acute glomerulonephritis including nephrotic-ranged proteinuria. Because her serologic test results were consistent with those for systemic lupus erythematosus (SLE), we performed laparoscopic renal biopsy that confirmed World Health Organization (WHO) class IV lupus nephritis. She was treated with steroids and intravenous cyclophosphamide puls...

  6. Semi-Automatic Segmentation of Autosomal Dominant Polycystic Kidneys using Random Forests

    OpenAIRE

    Sharma, Kanishka; Peter, Loic; Rupprecht, Christian; Caroli, Anna; Wang, Lichao; Remuzzi, Andrea; Baust, Maximilian; Navab, Nassir

    2015-01-01

    This paper presents a method for 3D segmentation of kidneys from patients with autosomal dominant polycystic kidney disease (ADPKD) and severe renal insufficiency, using computed tomography (CT) data. ADPKD severely alters the shape of the kidneys due to non-uniform formation of cysts. As a consequence, fully automatic segmentation of such kidneys is very challenging. We present a segmentation method with minimal user interaction based on a random forest classifier. One of the major novelties...

  7. Autosomal dominant cerebellar ataxia type III: a review of the phenotypic and genotypic characteristics

    OpenAIRE

    Fujioka Shinsuke; Sundal Christina; Wszolek Zbigniew K

    2013-01-01

    Abstract Autosomal Dominant Cerebellar Ataxia (ADCA) Type III is a type of spinocerebellar ataxia (SCA) classically characterized by pure cerebellar ataxia and occasionally by non-cerebellar signs such as pyramidal signs, ophthalmoplegia, and tremor. The onset of symptoms typically occurs in adulthood; however, a minority of patients develop clinical features in adolescence. The incidence of ADCA Type III is unknown. ADCA Type III consists of six subtypes, SCA5, SCA6, SCA11, SCA26, SCA30, and...

  8. A Mutation in a Skin-Specific Isoform of SMARCAD1 Causes Autosomal-Dominant Adermatoglyphia

    OpenAIRE

    Nousbeck, Janna; Burger, Bettina; Fuchs-Telem, Dana; Pavlovsky, Mor; Fenig, Shlomit; Sarig, Ofer; Itin, Peter; Sprecher, Eli

    2011-01-01

    Monogenic disorders offer unique opportunities for researchers to shed light upon fundamental physiological processes in humans. We investigated a large family affected with autosomal-dominant adermatoglyphia (absence of fingerprints) also known as the “immigration delay disease.” Using linkage and haplotype analyses, we mapped the disease phenotype to 4q22. One of the genes located in this interval is SMARCAD1, a member of the SNF subfamily of the helicase protein superfamily. We demonstrate...

  9. Dominant Inheritance of Field-Evolved Resistance to Fipronil in Plutella xylostella (Lepidoptera: Plutellidae).

    Science.gov (United States)

    Wang, Xingliang; Wu, Shuwen; Gao, Weiyue; Wu, Yidong

    2016-02-01

    A field-collected strain (HF) of Plutella xylostella (L.) showed 420-fold resistance to fipronil compared with a susceptible laboratory strain (Roth). The HF-R strain, derived from the HF strain by 25 generations of successive selection with fipronil in the laboratory, developed 2,200-fold resistance to fipronil relative to the Roth strain. The F(1) progeny of the reciprocal crosses between HF-R and Roth showed 640-fold (R♀ × S♂) and 1,380-fold (R♂ × S♀) resistance to fipronil, indicating resistance is inherited as an incompletely dominant trait. Analysis of progeny from a backcross (F1♂ × S♀) suggests that resistance is controlled by one major locus. The LC(50) of the R♂ × S♀ cross F(1) progeny is slightly but significantly higher than that of the R♀ × S♂ cross F(1) progeny, suggesting a minor resistance gene on the Z chromosome. Sequence analysis of PxGABARα1 (an Rdl-homologous GABA receptor gene of P. xylostella) from the HF-R strain identified two mutations A282S and A282G (corresponding to the A302S mutation of the Drosophila melanogaster Rdl gene), which have been previously implicated in fipronil resistance in several insect species including P. xylostella. PxGABARα1 was previously mapped to the Z chromosome of P. xylostella. In conclusion, fipronil resistance in the HF-R strain of P. xylostella was incompletely dominant, and controlled by a major autosomal locus and a sex-linked minor gene (PxGABARα1) on the Z chromosome. PMID:26511983

  10. Rare Variants in MME, Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies.

    Science.gov (United States)

    Auer-Grumbach, Michaela; Toegel, Stefan; Schabhüttl, Maria; Weinmann, Daniela; Chiari, Catharina; Bennett, David L H; Beetz, Christian; Klein, Dennis; Andersen, Peter M; Böhme, Ilka; Fink-Puches, Regina; Gonzalez, Michael; Harms, Matthew B; Motley, William; Reilly, Mary M; Renner, Wilfried; Rudnik-Schöneborn, Sabine; Schlotter-Weigel, Beate; Themistocleous, Andreas C; Weishaupt, Jochen H; Ludolph, Albert C; Wieland, Thomas; Tao, Feifei; Abreu, Lisa; Windhager, Reinhard; Zitzelsberger, Manuela; Strom, Tim M; Walther, Thomas; Scherer, Steven S; Züchner, Stephan; Martini, Rudolf; Senderek, Jan

    2016-09-01

    Axonal polyneuropathies are a frequent cause of progressive disability in the elderly. Common etiologies comprise diabetes mellitus, paraproteinaemia, and inflammatory disorders, but often the underlying causes remain elusive. Late-onset axonal Charcot-Marie-Tooth neuropathy (CMT2) is an autosomal-dominantly inherited condition that manifests in the second half of life and is genetically largely unexplained. We assumed age-dependent penetrance of mutations in a so far unknown gene causing late-onset CMT2. We screened 51 index case subjects with late-onset CMT2 for mutations by whole-exome (WES) and Sanger sequencing and subsequently queried WES repositories for further case subjects carrying mutations in the identified candidate gene. We studied nerve pathology and tissue levels and function of the abnormal protein in order to explore consequences of the mutations. Altogether, we observed heterozygous rare loss-of-function and missense mutations in MME encoding the metalloprotease neprilysin in 19 index case subjects diagnosed with axonal polyneuropathies or neurodegenerative conditions involving the peripheral nervous system. MME mutations segregated in an autosomal-dominant fashion with age-related incomplete penetrance and some affected individuals were isolated case subjects. We also found that MME mutations resulted in strongly decreased tissue availability of neprilysin and impaired enzymatic activity. Although neprilysin is known to degrade β-amyloid, we observed no increased amyloid deposition or increased incidence of dementia in individuals with MME mutations. Detection of MME mutations is expected to increase the diagnostic yield in late-onset polyneuropathies, and it will be tempting to explore whether substances that can elevate neprilysin activity could be a rational option for treatment. PMID:27588448

  11. Characterization of macular structure and function in two Swedish families with genetically identified autosomal dominant retinitis pigmentosa

    Science.gov (United States)

    Abdulridha-Aboud, Wissam; Kjellström, Ulrika; Andréasson, Sten

    2016-01-01

    Purpose To study the phenotype in two families with genetically identified autosomal dominant retinitis pigmentosa (adRP) focusing on macular structure and function. Methods Clinical data were collected at the Department of Ophthalmology, Lund University, Sweden, for affected and unaffected family members from two pedigrees with adRP. Examinations included optical coherence tomography (OCT), full-field electroretinography (ffERG), and multifocal electroretinography (mfERG). Molecular genetic screening was performed for known mutations associated with adRP. Results The mode of inheritance was autosomal dominant in both families. The members of the family with a mutation in the PRPF31 (p.IVS6+1G>T) gene had clinical features characteristic of RP, with severely reduced retinal rod and cone function. The degree of deterioration correlated well with increasing age. The mfERG showed only centrally preserved macular function that correlated well with retinal thinning on OCT. The family with a mutation in the RHO (p.R135W) gene had an extreme intrafamilial variability of the phenotype, with more severe disease in the younger generations. OCT showed pathology, but the degree of morphological changes was not correlated with age or with the mfERG results. The mother, with a de novo mutation in the RHO (p.R135W) gene, had a normal ffERG, and her retinal degeneration was detected merely with the reduced mfERG. Conclusions These two families demonstrate the extreme inter- and intrafamilial variability in the clinical phenotype of adRP. This is the first Swedish report of the clinical phenotype associated with a mutation in the PRPF31 (p.IVS6+1G>T) gene. Our results indicate that methods for assessment of the central retinal structure and function may improve the detection and characterization of the RP phenotype. PMID:27212874

  12. A new family of Greek origin maps to the CRD locus for autosomal dominant cone-rod dystrophy on 19q.

    OpenAIRE

    Papaioannou, M.; BESSANT, D.; Payne, A.; Bellingham, J.; Rougas, C; Loutradis-Anagnostou, A; Gregory-Evans, C; Balassopoulou, A; Bhattacharya, S.

    1998-01-01

    Retinal photoreceptor dystrophies (RD) are a highly heterogeneous group of genetic disorders of the retina, representing the most frequently inherited form of visual handicap, affecting approximately 1.5 million people world wide. To date, more than 40 genetic loci have been implicated in RD. One of them, the CORD2 locus, for an autosomal dominant form of cone-rod dystrophy (CRD), maps to chromosome 19q and has previously been reported in a single large family of British origin. We now report...

  13. Anesthetic Management and Postoperative Care of a Patient with CADASIL (Cerebral Arteriopathy, Autosomal Dominant, with Subcortical Infarcts and leukoencephalopathy for Cesarean Section

    Directory of Open Access Journals (Sweden)

    Sousan Rasooli

    2014-07-01

    Full Text Available CADASIL (cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy is an infrequent inherited small artery disease that could have anesthetic implications. However these have rarely been reported. We present an anesthetic experience of a female patient previously diagnosed with CADASIL, who had suffered an ischemic vascular cerebral accident with a MRI compatible with leukoencephalopathy, and who was dependent for daily activities, mood alterations, apathy, and urine incontinence. We discuss anesthetic management of CADASIL patient, considering protection from further cerebral ischemia.

  14. A total of 220 patients with autosomal dominant spastic paraplegia do not display mutations in the SLC33A1 gene (SPG42)

    OpenAIRE

    Schlipf, Nina A; Beetz, Christian; Schüle, Rebecca; Stevanin, Giovanni; Erichsen, Anne Kjersti; Forlani, Sylvie; Zaros, Cécile; Karle, Kathrin; Klebe, Stephan; Klimpe, Sven; Durr, Alexandra; Otto, Susanne; Tallaksen, Chantal M. E.; Riess, Olaf; Brice, Alexis

    2010-01-01

    The most frequent causes of autosomal dominant (AD) hereditary spastic paraplegias (HSP) (ADHSP) are mutations in the SPAST gene (SPG4 locus). However, roughly 60% of patients are negative for SPAST mutations, despite their family history being compatible with AD inheritance. A mutation in the gene for an acetyl-CoA transporter (SLC33A1) has recently been reported in one Chinese family to cause ADHSP-type SPG42. In this study, we screened 220 independent SPAST mutation-negative ADHSP samples ...

  15. The role of noise and positive feedback in the onset of autosomal dominant diseases

    Directory of Open Access Journals (Sweden)

    Bosl William J

    2010-06-01

    Full Text Available Abstract Background Autosomal dominant (AD diseases result when a single mutant or non-functioning gene is present on an autosomal chromosome. These diseases often do not emerge at birth. There are presently two prevailing theories explaining the expression of AD diseases. One explanation originates from the Knudson two-hit theory of hereditary cancers, where loss of heterozygosity or occurrence of somatic mutations impairs the function of the wild-type copy. While these somatic second hits may be sufficient for stable disease states, it is often difficult to determine if their occurrence necessarily marks the initiation of disease progression. A more direct consequence of a heterozygous genetic background is haploinsufficiency, referring to a lack of sufficient gene function due to reduced wild-type gene copy number; however, haploinsufficiency can involve a variety of additional mechanisms, such as noise in gene expression or protein levels, injury and second hit mutations in other genes. In this study, we explore the possible contribution to the onset of autosomal dominant diseases from intrinsic factors, such as those determined by the structure of the molecular networks governing normal cellular physiology. Results First, simple models of single gene insufficiency using the positive feedback loops that may be derived from a three-component network were studied by computer simulation using Bionet software. The network structure is shown to affect the dynamics considerably; some networks are relatively stable even when large stochastic variations in are present, while others exhibit switch-like dynamics. In the latter cases, once the network switches over to the disease state it remains in that state permanently. Model pathways for two autosomal dominant diseases, AD polycystic kidney disease and mature onset diabetes of youth (MODY were simulated and the results are compared to known disease characteristics. Conclusions By identifying the

  16. Evidence for locus heterogeneity in autosomal dominant limb-girdle muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Speer, M.C.; Stajich, J.M.; Gaskell, P.C. [Duke Univ. Medical School, Durham, NC (United States)] [and others

    1995-12-01

    Limb-girdle muscular dystrophy (LGMD) is a diagnostic classification encompassing a broad group of proximal myopathies. A gene for the dominant form of LGMD (LGMD1A) has recently been localized to a 7-cM region of chromosome 5q between D5S178 and IL9. We studied three additional dominant LGMD families for linkage to these two markers and excluded all from localization to this region, providing evidence for locus heterogeneity within the dominant form of LGMD. Although the patterns of muscle weakness were similar in all families studied, the majority of affected family members in the chromosome 5-linked pedigree have a dysarthric speech pattern, which is not present in any of the five unlinked families. The demonstration of heterogeneity within autosomal dominant LGMD is the first step in attempting to subclassify these families with similar clinical phenotypes on a molecular level. 33 refs., 1 fig., 2 tabs.

  17. A novel CRX mutation by whole-exome sequencing in an autosomal dominant cone-rod dystrophy pedigree

    Directory of Open Access Journals (Sweden)

    Qin-Kang Lu

    2015-12-01

    Full Text Available AIM: To identify the disease-causing gene mutation in a Chinese pedigree with autosomal dominant cone-rod dystrophy (adCORD. METHODS: A southern Chinese adCORD pedigree including 9 affected individuals was studied. Whole-exome sequencing (WES, coupling the Agilent whole-exome capture system to the Illumina HiSeq 2000 DNA sequencing platform was used to search the specific gene mutation in 3 affected family members and 1 unaffected member. After a suggested variant was found through the data analysis, the putative mutation was validated by Sanger DNA sequencing of samples from all available family members. RESULTS: The results of both WES and Sanger sequencing revealed a novel nonsense mutation c.C766T (p.Q256X within exon 5 of CRX gene which was pathogenic for adCORD in this family. The mutation could affect photoreceptor-specific gene expression with a dominant-negative effect and resulted in loss of the OTX tail, thus the mutant protein occupies the CRX-binding site in target promoters without establishing an interaction and, consequently, may block transactivation. CONCLUSION: All modes of Mendelian inheritance in CORD have been observed, and genetic heterogeneity is a hallmark of CORD. Therefore, conventional genetic diagnosis of CORD would be time-consuming and labor-intensive. Our study indicated the robustness and cost-effectiveness of WES in the genetic diagnosis of CORD.

  18. Diverging longitudinal changes in astrocytosis and amyloid PET in autosomal dominant Alzheimer’s disease

    Science.gov (United States)

    Saint-Aubert, Laure; Carter, Stephen F.; Almkvist, Ove; Farid, Karim; Schöll, Michael; Chiotis, Konstantinos; Thordardottir, Steinunn; Graff, Caroline; Wall, Anders; Långström, Bengt; Nordberg, Agneta

    2016-01-01

    See Schott and Fox (doi:10.1093/brain/awv405) for a scientific commentary on this article. Alzheimer’s disease is a multifactorial dementia disorder characterized by early amyloid-β, tau deposition, glial activation and neurodegeneration, where the interrelationships between the different pathophysiological events are not yet well characterized. In this study, longitudinal multitracer positron emission tomography imaging of individuals with autosomal dominant or sporadic Alzheimer’s disease was used to quantify the changes in regional distribution of brain astrocytosis (tracer 11C-deuterium-L-deprenyl), fibrillar amyloid-β plaque deposition (11C-Pittsburgh compound B), and glucose metabolism (18F-fluorodeoxyglucose) from early presymptomatic stages over an extended period to clinical symptoms. The 52 baseline participants comprised autosomal dominant Alzheimer’s disease mutation carriers (n = 11; 49.6 ± 10.3 years old) and non-carriers (n = 16; 51.1 ± 14.2 years old; 10 male), and patients with sporadic mild cognitive impairment (n = 17; 61.9 ± 6.4 years old; nine male) and sporadic Alzheimer’s disease (n = 8; 63.0 ± 6.5 years old; five male); for confidentiality reasons, the gender of mutation carriers is not revealed. The autosomal dominant Alzheimer’s disease participants belonged to families with known mutations in either presenilin 1 (PSEN1) or amyloid precursor protein (APPswe or APParc) genes. Sporadic mild cognitive impairment patients were further divided into 11C-Pittsburgh compound B-positive (n = 13; 62.0 ± 6.4; seven male) and 11C-Pittsburgh compound B-negative (n = 4; 61.8 ± 7.5 years old; two male) groups using a neocortical standardized uptake value ratio cut-off value of 1.41, which was calculated with respect to the cerebellar grey matter. All baseline participants underwent multitracer positron emission tomography scans, cerebrospinal fluid biomarker analysis and neuropsychological assessment. Twenty-six of the participants

  19. Diverging longitudinal changes in astrocytosis and amyloid PET in autosomal dominant Alzheimer's disease.

    Science.gov (United States)

    Rodriguez-Vieitez, Elena; Saint-Aubert, Laure; Carter, Stephen F; Almkvist, Ove; Farid, Karim; Schöll, Michael; Chiotis, Konstantinos; Thordardottir, Steinunn; Graff, Caroline; Wall, Anders; Långström, Bengt; Nordberg, Agneta

    2016-03-01

    See Schott and Fox (doi:10.1093/brain/awv405) for a scientific commentary on this article.Alzheimer's disease is a multifactorial dementia disorder characterized by early amyloid-β, tau deposition, glial activation and neurodegeneration, where the interrelationships between the different pathophysiological events are not yet well characterized. In this study, longitudinal multitracer positron emission tomography imaging of individuals with autosomal dominant or sporadic Alzheimer's disease was used to quantify the changes in regional distribution of brain astrocytosis (tracer (11)C-deuterium-L-deprenyl), fibrillar amyloid-β plaque deposition ((11)C-Pittsburgh compound B), and glucose metabolism ((18)F-fluorodeoxyglucose) from early presymptomatic stages over an extended period to clinical symptoms. The 52 baseline participants comprised autosomal dominant Alzheimer's disease mutation carriers (n = 11; 49.6 ± 10.3 years old) and non-carriers (n = 16; 51.1 ± 14.2 years old; 10 male), and patients with sporadic mild cognitive impairment (n = 17; 61.9 ± 6.4 years old; nine male) and sporadic Alzheimer's disease (n = 8; 63.0 ± 6.5 years old; five male); for confidentiality reasons, the gender of mutation carriers is not revealed. The autosomal dominant Alzheimer's disease participants belonged to families with known mutations in either presenilin 1 (PSEN1) or amyloid precursor protein (APPswe or APParc) genes. Sporadic mild cognitive impairment patients were further divided into (11)C-Pittsburgh compound B-positive (n = 13; 62.0 ± 6.4; seven male) and (11)C-Pittsburgh compound B-negative (n = 4; 61.8 ± 7.5 years old; two male) groups using a neocortical standardized uptake value ratio cut-off value of 1.41, which was calculated with respect to the cerebellar grey matter. All baseline participants underwent multitracer positron emission tomography scans, cerebrospinal fluid biomarker analysis and neuropsychological assessment. Twenty-six of the participants

  20. Copeptin, a Surrogate Marker of Vasopressin, Is Associated with Disease Severity in Autosomal Dominant Polycystic Kidney Disease

    NARCIS (Netherlands)

    Meijer, Esther; Bakker, Stephan J. L.; van der Jagt, Eric J.; Navis, Gerjan; de Jong, Paul E.; Struck, Joachim; Gansevoort, Ron T.

    2011-01-01

    Background and objectives Experimental studies suggest a detrimental role for vasopressin in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). However, it is unknown whether endogenous vasopressin concentration is associated with disease severity in patients with ADPKD. Desig

  1. Clinical and genetic analysis of a four-generation family with a distinct autosomal dominant cerebellar ataxia

    NARCIS (Netherlands)

    Schelhaas, H J; Ippel, P F; Hageman, G; Sinke, R J; van der Laan, E N; Beemer, F A

    2001-01-01

    The autosomal dominant cerebellar ataxias (ADCAs) are a heterogeneous group of neurodegenerative disorders characterised by progressive cerebellar dysfunction in combination with a variety of other associative features. Since 1993 ADCAs have been increasingly characterised in terms of their genetic

  2. Genetic linkage studies in autosomal dominant ataxia families with an MJD phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, I.; Lopes-Cendes, I.; Paciel, P. [McGill Univ., Montreal (Canada)] [and others

    1994-09-01

    Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar degeneration which was originally described in patients originating from the Portuguese islands of the Azores. The first non-Portuguese kindred was described in 1979 and was an American black family originating from North Carolina. Since then the number of pedigrees of non-Azorean, non-Portuguese origin has increased with families being reported from other European countries, as well as Brazil, Japan, India, The United States and Australia. The autosomal dominant ataxias are a clinically and genetically heterogeneous group of disorders. To date, genetic analysis of families with autosomal dominant ataxias has permitted the identification of four loci, the SCA1 (spinocerebellar ataxia type 1) locus on chromosome 6p, the SCA2 locus on chromosome 12q, a third locus on chromosome 14q, the MJD/SCA3 and, more recently, the DRPLA (Dentatorubral-pallidoluysian atrophy) locus on chromosome 12p. We ascertained a total of 181 individuals with 60 affected from eight Indian, two Brazilian and one Sicilian-American family; all of them have received the clinical diagnosis of MJD. Recently, we have begun molecular genetic studies in these families in order to test these four candidate regions. The SCA1 mutation and the DRPLA mutation has been found to be an expansion of a CAG repeat. Direct analysis of the SCA1 and DRPLA expansion has been performed in all families and no expansion was found in the affected individuals. We are now running flanking markers for the SCA2 and MJD/SCA3 loci. These results will also be presented.

  3. Autosomal-Dominant Multiple Pterygium Syndrome Is Caused by Mutations in MYH3

    Science.gov (United States)

    Chong, Jessica X.; Burrage, Lindsay C.; Beck, Anita E.; Marvin, Colby T.; McMillin, Margaret J.; Shively, Kathryn M.; Harrell, Tanya M.; Buckingham, Kati J.; Bacino, Carlos A.; Jain, Mahim; Alanay, Yasemin; Berry, Susan A.; Carey, John C.; Gibbs, Richard A.; Lee, Brendan H.; Krakow, Deborah; Shendure, Jay; Nickerson, Deborah A.; Bamshad, Michael J.; Shendure, Jay; Nickerson, Deborah A.; Abecasis, Gonçalo R.; Anderson, Peter; Blue, Elizabeth Marchani; Annable, Marcus; Browning, Brian L.; Buckingham, Kati J.; Chen, Christina; Chin, Jennifer; Chong, Jessica X.; Cooper, Gregory M.; Davis, Colleen P.; Frazar, Christopher; Harrell, Tanya M.; He, Zongxiao; Jain, Preti; Jarvik, Gail P.; Jimenez, Guillaume; Johanson, Eric; Jun, Goo; Kircher, Martin; Kolar, Tom; Krauter, Stephanie A.; Krumm, Niklas; Leal, Suzanne M.; Luksic, Daniel; Marvin, Colby T.; McMillin, Margaret J.; McGee, Sean; O’Reilly, Patrick; Paeper, Bryan; Patterson, Karynne; Perez, Marcos; Phillips, Sam W.; Pijoan, Jessica; Poel, Christa; Reinier, Frederic; Robertson, Peggy D.; Santos-Cortez, Regie; Shaffer, Tristan; Shephard, Cindy; Shively, Kathryn M.; Siegel, Deborah L.; Smith, Joshua D.; Staples, Jeffrey C.; Tabor, Holly K.; Tackett, Monica; Underwood, Jason G.; Wegener, Marc; Wang, Gao; Wheeler, Marsha M.; Yi, Qian; Bamshad, Michael J.

    2015-01-01

    Multiple pterygium syndrome (MPS) is a phenotypically and genetically heterogeneous group of rare Mendelian conditions characterized by multiple pterygia, scoliosis, and congenital contractures of the limbs. MPS typically segregates as an autosomal-recessive disorder, but rare instances of autosomal-dominant transmission have been reported. Whereas several mutations causing recessive MPS have been identified, the genetic basis of dominant MPS remains unknown. We identified four families affected by dominantly transmitted MPS characterized by pterygia, camptodactyly of the hands, vertebral fusions, and scoliosis. Exome sequencing identified predicted protein-altering mutations in embryonic myosin heavy chain (MYH3) in three families. MYH3 mutations underlie distal arthrogryposis types 1, 2A, and 2B, but all mutations reported to date occur in the head and neck domains. In contrast, two of the mutations found to cause MPS in this study occurred in the tail domain. The phenotypic overlap among persons with MPS, coupled with physical findings distinct from other conditions caused by mutations in MYH3, suggests that the developmental mechanism underlying MPS differs from that of other conditions and/or that certain functions of embryonic myosin might be perturbed by disruption of specific residues and/or domains. Moreover, the vertebral fusions in persons with MPS, coupled with evidence of MYH3 expression in bone, suggest that embryonic myosin plays a role in skeletal development. PMID:25957469

  4. Renal replacement therapy for autosomal dominant polycystic kidney disease (ADPKD) in Europe

    DEFF Research Database (Denmark)

    Spithoven, Edwin M; Kramer, Anneke; Meijer, Esther;

    2014-01-01

    on RRT prevalence and survival on RRT in 12 European countries with 208 million inhabitants. We studied four 5-year periods (1991-2010). Survival analysis was performed by the Kaplan-Meier method and by Cox proportional hazards regression. RESULTS: From the first to the last study period, the......BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the fourth most common renal disease requiring renal replacement therapy (RRT). Still, there are few epidemiological data on the prevalence of, and survival on RRT for ADPKD. METHODS: This study used data from the ERA-EDTA Registry...

  5. Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy

    DEFF Research Database (Denmark)

    Winkelmann, Juliane; Lin, Ling; Schormair, Barbara;

    2012-01-01

    Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is characterized by late onset (30-40 years old) cerebellar ataxia, sensory neuronal deafness, narcolepsy-cataplexy and dementia. We performed exome sequencing in five individuals from three ADCA-DN kindreds and identified DNMT.......GLY605Ala mutation was subsequently identified. Narcolepsy and deafness were the first symptoms to appear in all pedigrees, followed by ataxia. DNMT1 is a widely expressed DNA methyltransferase maintaining methylation patterns in development, and mediating transcriptional repression by direct binding to...

  6. Macular sensitivity and fixation patterns in patients with autosomal dominant optic atrophy

    DEFF Research Database (Denmark)

    Rönnbäck, Cecilia; Larsen, Michael

    2014-01-01

    INTRODUCTION: The objective of this study was to test macular sensitivity, fixation stability and fixation location using microperimetry in patients with autosomal dominant optic atrophy (ADOA) and mutation-free relatives. MATERIAL AND METHODS: This was a cross-sectional study of 43 patients with...... exon 28 (2826 delT) mutation in OPA1 (age 11.7-71.5 years, best-corrected visual acuity (BCVA) 20/24-20/13). The patients and 49 mutation-free first-degree relatives (BCVA 20/25-20/10) underwent ophthalmic examination including macular microperimetry out to 12° eccentricity with registration of...

  7. A novel retinal oscillation mechanism in an autosomal dominant photoreceptor degeneration mouse model

    OpenAIRE

    Hung-Ya Tu; Adam Rory McQuiston; Chuan-Chin Chiao; Ching-Kang Chen

    2016-01-01

    It has been shown in rd1 and rd10 models of photoreceptor degeneration (PD) that inner retinal neurons display spontaneous and rhythmic activities. Furthermore, the rhythmic activity has been shown to require the gap junction protein connexin 36, which is likely located in AII amacrine cells (AII-ACs). In the present study, an autosomal dominant PD model called rhoΔCTA, whose rods overexpress a C-terminally truncated mutant rhodopsin and degenerate with a rate similar to that of rd1, was used...

  8. A Novel Retinal Oscillation Mechanism in an Autosomal Dominant Photoreceptor Degeneration Mouse Model

    OpenAIRE

    Tu, Hung-Ya; Chen, Yu-Jiun; McQuiston, Adam R.; Chiao, Chuan-Chin; Chen, Ching-Kang

    2016-01-01

    It has been shown in rd1 and rd10 models of photoreceptor degeneration (PD) that inner retinal neurons display spontaneous and rhythmic activities. Furthermore, the rhythmic activity has been shown to require the gap junction protein connexin 36, which is likely located in AII amacrine cells (AII-ACs). In the present study, an autosomal dominant PD model called rhoΔCTA, whose rods overexpress a C-terminally truncated mutant rhodopsin and degenerate with a rate similar to that of rd1, was used...

  9. Will introduction of tolvaptan change clinical practice in autosomal dominant polycystic kidney disease?

    Science.gov (United States)

    Horie, Shigeo

    2015-07-01

    The vasopressin inhibitor tolvaptan is clinically effective in slowing growth of renal cysts and reduction in estimated glomerular filtration rate (eGFR) in autosomal dominant polycystic kidney disease (ADPKD), but these effects are mitigated by the associated polyuria. Changes of total kidney volume, eGFR, and symptoms will guide physicians and patients in tolvaptan treatment. Guidance about when to initiate treatment in the course of ADPKD may be forthcoming. Ongoing long-term observations will inform future recommendations about tolvaptan use in ADPKD. PMID:26126090

  10. Cyst growth, polycystins, and primary cilia in autosomal dominant polycystic kidney disease

    OpenAIRE

    Lee, Seung Hun; Somlo, Stefan

    2014-01-01

    The primary cilium of renal epithelia acts as a transducer of extracellular stimuli. Polycystin (PC)1 is the protein encoded by the PKD1 gene that is responsible for the most common and severe form of autosomal dominant polycystic kidney disease (ADPKD). PC1 forms a complex with PC2 via their respective carboxy-terminal tails. Both proteins are expressed in the primary cilia. Mutations in either gene affect the normal architecture of renal tubules, giving rise to ADPKD. PC1 has been proposed ...

  11. Autosomal dominant polycystic kidney disease: recent advances in clinical management [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Zhiguo Mao

    2016-08-01

    Full Text Available The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD go back at least 500 years to the late 16th century. Advances in understanding disease presentation and pathophysiology have mirrored the progress of clinical medicine in anatomy, pathology, physiology, cell biology, and genetics. The identification of PKD1 and PKD2, the major genes mutated in ADPKD, has stimulated major advances, which in turn have led to the first approved drug for this disorder and a fresh reassessment of patient management in the 21st century. In this commentary, we consider how clinical management is likely to change in the coming decade.

  12. Familial Clustering of Unexplained Transient Respiratory Distress in 12 Newborns from Three Unrelated Families Suggests an Autosomal-Recessive Inheritance

    Directory of Open Access Journals (Sweden)

    Andrea Guala

    2007-01-01

    Full Text Available We report on 12 near-term babies from three families in which an unexplained transient respiratory distress was observed. No known risk factor was present in any family and no sequelae were recorded at follow-up. The most common causes of respiratory distress at birth are Neonatal Respiratory Distress Syndrome (NRD and Transient Tachypnea of the Newborn (TTN, and their cumulative incidence is estimated to be about 2%. Genetic factors have been identified in NRD (surfactant genes or suggested for TTN (genes affecting lung liquid clearance. Survivors from NRD may develop clinically relevant sequelae, while TTN does not cause any problem later in life. Our cases do not immediately fit NRD or TTN, while familial recurrence suggests the existence of a previously unreported subgroup on patients with respiratory distress for which autosomal-recessive inheritance is likely.

  13. Dominant inherited distal spinal muscular atrophy with atrophic and hypertrophic calves

    NARCIS (Netherlands)

    Groen, R J; Sie, O G; van Weerden, T W

    1993-01-01

    The clinical, electrophysiological, radiological and morphological data of 3 members of a family with autosomal dominant distal spinal muscular atrophy (DSMA) are reported. One patient has the clinical picture of peroneal muscular atrophy with atrophic calves. His father and sister suffer from cramp

  14. Evidence for locus heterogeneity in human autosomal dominant split hand/split foot malformation

    Energy Technology Data Exchange (ETDEWEB)

    Palmer, S.E.; Wijsman, E.M.; Stephens, K.; Evans, J.P. (Univ. of Washington School of Medicine, Seattle, WA (United States)); Scherer, S.W.; Tsui, L.C. (Univ. of Toronto (Canada)); Kukolich, M. (Genetic Screening and Counseling Service, Denton, TX (United States))

    1994-07-01

    Split hand/split foot (SHSF; also known as ectrodactyly) is a human developmental disorder characterized by missing central digits and other distal limb malformations. An association between SHSF and cytogenetically visible rearrangements of chromosome 7 at bands q21-q22 provides compelling evidence for the location of a causative gene at this location, and the locus has been designated SHFD1. In the present study, marker loci were localized to the SHFD1 critical region through the analysis of somatic cell hybrids derived from individuals with SHSF and cytogenetic abnormalities involving the 7q21-q22 region. Combined genetic and physical data suggest that the order of markers in the SHFD1 critical region is cen-D7S492-D7S527-(D7S479-D7S491)-SHFD1-D7S553-D7S518-qter. Dinucleotide repeat polymorphisms at three of these loci were used to test for linkage of SHSF to this region in a large pedigree that demonstrates autosomal dominant SHSF. Evidence against linkage of the SHSF gene to 7q21-q22 was obtained in this pedigree. Therefore, combined molecular and genetic data provide evidence for locus heterogeneity in autosomal dominant SHSF. The authors propose the name SHSF2 for this second locus. 34 refs., 4 figs., 1 tab.

  15. Oculopharyngeal Weakness, Hypophrenia, Deafness, and Impaired Vision: A Novel Autosomal Dominant Myopathy with Rimmed Vacuoles

    Science.gov (United States)

    Chen, Ting; Lu, Xiang-Hui; Wang, Hui-Fang; Ban, Rui; Liu, Hua-Xu; Shi, Qiang; Wang, Qian; Yin, Xi; Pu, Chuan-Qiang

    2016-01-01

    Background: Myopathies with rimmed vacuoles are a heterogeneous group of muscle disorders with progressive muscle weakness and varied clinical manifestations but similar features in muscle biopsies. Here, we describe a novel autosomal dominant myopathy with rimmed vacuoles in a large family with 11 patients of three generations affected. Methods: A clinical study including family history, obstetric, pediatric, and development history was recorded. Clinical examinations including physical examination, electromyography (EMG), serum creatine kinase (CK), bone X-rays, and brain magnetic resonance imaging (MRI) were performed in this family. Open muscle biopsies were performed on the proband and his mother. To find the causative gene, the whole-exome sequencing was carried out. Results: Disease onset was from adolescence to adulthood, but the affected patients of the third generation presented an earlier onset and more severe clinical manifestations than the older generations. Clinical features were characterized as dysarthria, dysphagia, external ophthalmoplegia, limb weakness, hypophrenia, deafness, and impaired vision. However, not every patient manifested all symptoms. Serum CK was mildly elevated and EMG indicated a myopathic pattern. Brain MRI showed cerebellum and brain stem mildly atrophy. Rimmed vacuoles and inclusion bodies were observed in muscle biopsy. The whole-exome sequencing was performed, but the causative gene has not been found. Conclusions: We reported a novel autosomal dominant myopathy with rimmed vacuoles characterized by dysarthria, dysphagia, external ophthalmoplegia, limb weakness, hypophrenia, deafness, and impaired vision, but the causative gene has not been found and needs further study. PMID:27453229

  16. Therapeutic mTOR inhibition in autosomal dominant polycystic kidney disease: What is the appropriate serum level?

    Science.gov (United States)

    Canaud, G; Knebelmann, B; Harris, P C; Vrtovsnik, F; Correas, J-M; Pallet, N; Heyer, C M; Letavernier, E; Bienaimé, F; Thervet, E; Martinez, F; Terzi, F; Legendre, C

    2010-07-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease, and sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been shown to significantly retard cyst expansion in animal models. The optimal therapeutic dose of sirolimus is not yet defined. Here, we report the history of a previously unknown ADPKD deceased donor whose kidneys were engrafted in two different recipients. One of the two received an immunosuppressive regimen based on sirolimus for 5 years while the other did not. After transplantation, both patients developed severe transplant cystic disease. Donor DNA sequence identified a new hypomorphic mutation in PKD1. The rate of cyst growth was identical in the two patients regardless of the treatment. While sirolimus treatment reduced the activation of mTOR in peripheral blood mononuclear cells, it failed to prevent mTOR activation in kidney tubular cells, this could account for the inefficiency of treatment on cyst growth. Together, our results suggest that the dose of sirolimus required to inhibit mTOR varies according to the tissue. PMID:20642692

  17. A de novo mutation in KCNN3 associated with autosomal dominant idiopathic non-cirrhotic portal hypertension.

    Science.gov (United States)

    Koot, Bart G P; Alders, Marielle; Verheij, Joanne; Beuers, Ulrich; Cobben, Jan M

    2016-04-01

    Non-cirrhotic portal hypertension is characterized by histopathological abnormalities in the liver, mostly affecting small intrahepatic portal veins that cause portal hypertension in the absence of cirrhosis. It can be secondary to coagulation disorders or toxic agents. However, most cases are idiopathic non-cirrhotic portal hypertension (INCPH) and familial cases are rare. We report a family in which a father and three of his four children conceived with three different mothers are affected by INCPH. Whole exome and Sanger sequencing showed the father to have a de novo single nucleotide substitution c.1348G>C in the KCNN3 gene that was transmitted to all three of his affected offspring. The KCNN3 gene encodes small conductance calcium-activated potassium (SK) channel 3. SK channels are involved in the regulation of arterial and venous vascular tone by causing smooth muscle relaxation on activation. No data exist on the expression and function of SK channels in portal veins. The autosomal dominant inheritance in this unique pedigree and the single de novo mutation identified, strongly suggests that KCNN3 mutations have a pathogenetic role in INCPH. PMID:26658685

  18. Prevalence and novelty of PRPF31 mutations in French autosomal dominant rod-cone dystrophy patients and a review of published reports

    Directory of Open Access Journals (Sweden)

    Mohand-Saïd Saddek

    2010-10-01

    Full Text Available Abstract Background Rod-cone dystrophies are heterogeneous group of inherited retinal disorders both clinically and genetically characterized by photoreceptor degeneration. The mode of inheritance can be autosomal dominant, autosomal recessive or X-linked. The purpose of this study was to identify mutations in one of the genes, PRPF31, in French patients with autosomal dominant RP, to perform genotype-phenotype correlations of those patients, to determine the prevalence of PRPF31 mutations in this cohort and to review previously identified PRPF31 mutations from other cohorts. Methods Detailed phenotypic characterization was performed including precise family history, best corrected visual acuity using the ETDRS chart, slit lamp examination, kinetic and static perimetry, full field and multifocal ERG, fundus autofluorescence imaging and optic coherence tomography. For genetic diagnosis, genomic DNA of ninety families was isolated by standard methods. The coding exons and flanking intronic regions of PRPF31 were PCR amplified, purified and sequenced in the index patient. Results We showed for the first time that 6.7% cases of a French adRP cohort have a PRPF31 mutation. We identified in total six mutations, which were all novel and not detected in ethnically matched controls. The mutation spectrum from our cohort comprises frameshift and splice site mutations. Co-segregation analysis in available family members revealed that each index patient and all affected family members showed a heterozygous mutation. In five families incomplete penetrance was observed. Most patients showed classical signs of RP with relatively preserved central vision and visual field. Conclusion Our studies extended the mutation spectrum of PRPF31 and as previously reported in other populations, it is a major cause of adRP in France.

  19. Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment

    DEFF Research Database (Denmark)

    Rendtorff, Nanna D; Lodahl, Marianne; Boulahbel, Houda; Johansen, Ida R; Pandya, Arti; Welch, Katherine O; Norris, Virginia W; Arnos, Kathleen S; Bitner-Glindzicz, Maria; Emery, Sarah B; Mets, Marilyn B; Fagerheim, Toril; Eriksson, Kristina; Hansen, Lars; Bruhn, Helene; Möller, Claes; Lindholm, Sture; Ensgaard, Stefan; Lesperance, Marci M; Tranebjaerg, Lisbeth

    2011-01-01

    Optic atrophy (OA) and sensorineural hearing loss (SNHL) are key abnormalities in several syndromes, including the recessively inherited Wolfram syndrome, caused by mutations in WFS1. In contrast, the association of autosomal dominant OA and SNHL without other phenotypic abnormalities is rare, and...... DNA deletions were detected in muscle from one p.A684V patient analyzed. Finally, wolframin p.A684V mutant ectopically expressed in HEK cells showed reduced protein levels compared to wild-type wolframin, strongly indicating that the mutation is disease-causing. Our data support OA and SNHL as a...... phenotype caused by dominant mutations in WFS1 in these additional eight families. Importantly, our data provide the first evidence that a single, recurrent mutation in WFS1, p.A684V, may be a common cause of ADOA and SNHL, similar to the role played by the p.R445H mutation in OPA1. Our findings suggest...

  20. Late onset autosomal dominant cerebellar ataxia a family description and linkage analysis with the hla system

    Directory of Open Access Journals (Sweden)

    Walter O. Arruda

    1991-09-01

    Full Text Available A family suffering an autosomal dominant form of late onset hereditary cerebellar ataxia is described. Eight affected family members were personally studied, and data from another four were obtained through anamnesis. The mean age of onset was 37.1±5.4 years (27-47 years. The clinical picture consisted basically of a pure ataxic cerebellar syndrome. CT-scan disclosed diffuse cerebellar atrophy with relative sparing of the brainstem (and no involvement of supratentorial structures. Neurophysiological studies (nerve conduction, VEP and BAEP were normal. Twenty-six individuals were typed for HLA histocompatibility antigens. Lod scores were calculated with the computer program LINKMAP. Close linkage of the ataxia gene with the HLA system in this family could be excluded - 0==0,02, z=(-2,17 - and the overall analysis of the lod scores suggest another chromossomal location than chromosome 6.

  1. AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD IN A LARGE IRANIAN FAMILY

    Directory of Open Access Journals (Sweden)

    D.D. Farhud

    1999-08-01

    Full Text Available Study of a family with autosomal dominant polycystic kidney diseases (ADPKD in five generations, including 96 healthy and 47 affected individuals, has been carried out in Tehran. Investigation on individuals, including final diagnoses by clinical findings, sonography, radiography and laboratory results, have Lead to the completion of genealogical chart of the family. The affected individuals have reached a stage of the disease with confirmed occurrence of renal damages. Uncertain diagnoses, unconfirmed statements of the family members about probable presence of the disease in some other members, and also the death of some members by other reasons were not possible to be registered in the chart. Up to now the chart has been the largest and the most complete in Iran, compared with the ones reported in the available literature.

  2. Clinical features and linkage analysis for a Chinese family with autosomal dominant central areolar choroidal dystrophy

    Institute of Scientific and Technical Information of China (English)

    MA Kai; LIU Ning-pu; YANG Xiu-fen; HAN Cui; ZHANG Ning; XU Jun; LIU Shou-bin; LU Hal; Torkel Snellingen; WANG Ning-li

    2009-01-01

    Background A Chinese family with autosomal dominant central areolar choroidal dystrophy (CACD) was identified.The purpose of this study was to collect the clinical findings from the family and to identify the genetic entity by linkage nalysis.Methods Forty-three individuals from 3 generations of the family underwent ophthalmologic examinations, including best-corrected visual acuity, examination of the anterior segments, and inspection of the ocular fundus after pharmacologic mydriasis. Affected family members further underwent color vision test, color fundus photography,fluorescein angiography, automated perimetry, and electroretinography. The family was followed up for 30 months.Peripheral venous blood or buccal swabs were collected from each family member and genomic DNA was extracted.Linkage analysis was performed for candidate genes or loci using microsatellite markers.Results Seven family members in 3 continuous generations were diagnosed as having autosomal dominant CACD.The family showed progressive development of the disease, affecting both male and female. Age of onset of visual disturbances varied between 11 and 50 years. Phenotypic variability among affected individuals was apparent and ranged from relatively normal-appearing fundus with mild parafoveal pigment mottling to geographic atrophy of the macula. Fluorescein angiography showed hyperfluorescent parafoveal changes in early stage or well-demarcated area of chorioretinal atrophy with enhanced visibility of the residual underlying choroidal vessels in the late stage. Peripheral retina and visual fields were normal in affected individuals. Electroretinogram showed normal or mild reduction in the photopic amplitude. Eight candidate genes (STGD4, RCD1, peripherin/RDS, GUCA1A, RIMS1, UNC119, GUC Y2D, and AIPL1) and two genetic loci (4p15.2-16.3, and 17p13) were excluded to be responsible for the disease by linkage analysis.Conclusions The clinical findings of this Chinese family with CACD shared

  3. Missense mutations in ITPR1 cause autosomal dominant congenital nonprogressive spinocerebellar ataxia

    Directory of Open Access Journals (Sweden)

    Huang Lijia

    2012-09-01

    Full Text Available Abstract Background Congenital nonprogressive spinocerebellar ataxia is characterized by early gross motor delay, hypotonia, gait ataxia, mild dysarthria and dysmetria. The clinical presentation remains fairly stable and may be associated with cerebellar atrophy. To date, only a few families with autosomal dominant congenital nonprogressive spinocerebellar ataxia have been reported. Linkage to 3pter was demonstrated in one large Australian family and this locus was designated spinocerebellar ataxia type 29. The objective of this study is to describe an unreported Canadian family with autosomal dominant congenital nonprogressive spinocerebellar ataxia and to identify the underlying genetic causes in this family and the original Australian family. Methods and Results Exome sequencing was performed for the Australian family, resulting in the identification of a heterozygous mutation in the ITPR1 gene. For the Canadian family, genotyping with microsatellite markers and Sanger sequencing of ITPR1 gene were performed; a heterozygous missense mutation in ITPR1 was identified. Conclusions ITPR1 encodes inositol 1,4,5-trisphosphate receptor, type 1, a ligand-gated ion channel that mediates calcium release from the endoplasmic reticulum. Deletions of ITPR1 are known to cause spinocerebellar ataxia type 15, a distinct and very slowly progressive form of cerebellar ataxia with onset in adulthood. Our study demonstrates for the first time that, in addition to spinocerebellar ataxia type 15, alteration of ITPR1 function can cause a distinct congenital nonprogressive ataxia; highlighting important clinical heterogeneity associated with the ITPR1 gene and a significant role of the ITPR1-related pathway in the development and maintenance of the normal functions of the cerebellum.

  4. Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR caused by a VDR mutation: A novel mechanism of dominant inheritance

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Isojima

    2015-06-01

    Full Text Available Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR is caused by mutations in the VDR gene, and its inheritance is autosomal recessive. In this report, we aimed to confirm whether HVDRR is occasionally inherited as a dominant trait. An 18-month-old Japanese boy was evaluated for short stature and bowlegs. His father had been treated for rickets during childhood, and his paternal grandfather had bowlegs. We diagnosed him with HVDRR based on laboratory data and radiographic evidence of rickets. Sequence analyses of VDR were performed, and the functional consequences of the detected mutations were analyzed for transcriptional activity, ligand binding, and interaction with the retinoid X receptor, cofactors, and the vitamin D response element (VDRE. A novel mutation (Q400LfsX7 and a reported variant (R370H were identified in the patient. Heterozygous Q400LfsX7 was detected in his father, and heterozygous R370H was detected in his healthy mother. Functional studies revealed that the transcriptional activity of Q400LfsX7-VDR was markedly disturbed. The mutant had a dominant-negative effect on wild-type-VDR, and the ligand binding affinity of Q400LfsX7-VDR was completely impaired. Interestingly, Q400LfsX7-VDR had a strong interaction with corepressor NCoR and could interact with VDRE without the ligand. R370H-VDR was functionally similar to wild-type-VDR. In conclusion, we found a dominant-negative mutant of VDR causing dominantly inherited HVDRR through a constitutive corepressor interaction, a mechanism similar to that in dominantly inherited thyroid hormone receptor mutations. Our report together with a reported pedigree suggested a distinct inheritance of HVDRR and enriched our understanding of VDR abnormalities.

  5. Combined partial deficiency of muscle carnitine palmitoyltransferase and carnitine with autosomal dominant inheritance.

    OpenAIRE

    Ionasescu, V; Hug, G.; Hoppel, C

    1980-01-01

    The authors studied a 53 year old woman and her 22 year old son with episodes of paroxysmal muscle cramps and dark urines lasting several hours related to high fat diet and strenuous physical exercise beginning on both at age 14 years. The father, paternal uncle, paternal grandfather and another son of the mother also had paroxysmal muscle cramps. The two studied cases showed normal findings for physical evaluation, blood lactate after ischemic exercise, and muscle histology (light and electr...

  6. Frequency analysis of autosomal dominant spinocerebellar ataxias in mainland Chinese patients and clinical and molecular characterization of spinocerebellar ataxia type 6

    Institute of Scientific and Technical Information of China (English)

    JIANG Hong; TANG Bei-sha; XU Bo; ZHAO Guo-hua; SHEN Lu; TANG Jian-guang; LI Qing-hua; XIA Kun

    2005-01-01

    Background Dominantly inherited spinocerebellar ataxia (SCA) is a clinically and genetically heterogeneous group of neurodegenerative disorders. This study was to further assess the frequency of SCA1 (spinocerebellar ataxia type 1), SCA2, SCA3/MJD (spinocerebellar ataxia type 3/Machado-Joseph disease), SCA6, SCA7, SCA8, SCA10, SCA12, SCA14, SCA17 and DRPLA (dentatorubro-pallidoluysian atrophy) in mainland Chinese, and to specifically characterize mainland Chinese patients with SCA6 in terms of clinical and molecular features.Methods Using a molecular approach, we investigated SCA in 120 mainland Chinese families with dominantly inherited ataxias and in 60 mainland Chinese patients with sporadic ataxias. Clinical and molecular features of SCA6 were further characterized in 13 patients from 4 families. Results SCA3/MJD was the most common type of autosomal dominant SCA in mainland Chinese, accounting for 83 patients from 59 families (49.2%), followed by SCA2[8(6.7%)], SCA1[7(5.8%)], SCA6[4(3.3%)], SCA7[1(0.8%)], SCA8(0%), SCA10(0%), SCA12(0%), SCA14(0%), SCA17(0%) and DRPLA(0%). The genes responsible for 41 (34.2%) of dominantly inherited SCA families remain to be determined. Among the 60 patients with sporadic ataxias in the present series, 3 (5.0%) was found to harbor SCA3 mutations while none was found to harbor SCA6 mutations. In the 4 families with SCA6, significant anticipation was found in the absence of genetic instability on transmission.Conclusion A geographic cluster of families with SCA6 subtype was initially identified in a mainland Chinese population.

  7. Genetics of dementias, Part 4: A spectrum of mutations responsible for the familial autosomal dominant form of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Anna Kowalska

    2009-12-01

    Full Text Available Fifty years ago it was demonstrated that some patients with Alzheimer’s disease (AD had an autosomal dominant Mendelian pattern of disease inheritance. Familial and early-onset cases (familial Alzheimer’s disease, FAD are rather rare and account for only a few percent of the total population of patients. Mutations of the genes for amyloid precursor protein (APP, presenilin 1 (PSEN1, and presenilin 2 (PSEN2 are responsible for development of the disease in 50 percent of patients with FAD. The identification of mutations in FAD genes leads to a better understand of the molecular basis of the cellular pathways leading to neurodegeneration. With the detection of genetic defects responsible for FAD, there is considerable interest in the application of this genetic information in medical practice through genetic testing and counseling for families with Alzheimer’s disease.

  8. Kidney Function and Plasma Copeptin Levels in Healthy Kidney Donors and Autosomal Dominant Polycystic Kidney Disease Patients

    NARCIS (Netherlands)

    Zittema, Debbie; van den Berg, Else; Meijer, Esther; Boertien, Wendy E.; Muller Kobold, Anneke C.; Franssen, Casper F. M.; de Jong, Paul E.; Bakker, Stephan J. L.; Navis, Gerjan; Gansevoort, Ron T.

    2014-01-01

    Background and objectives Plasma copeptin, a marker of arginine vasopressin, is elevated in patients with autosomal dominant polycystic kidney disease and predicts disease progression. It is unknown whether elevated copeptin levels result from decreased kidney clearance or as compensation for impair

  9. Genotype-phenotype heterogeneity of ganglion cell and inner plexiform layer deficit in autosomal-dominant optic atrophy

    DEFF Research Database (Denmark)

    Rönnbäck, Cecilia; Nissen, Claus; Almind, Gitte J; Grønskov, Karen; Milea, Dan; Larsen, Michael

    2015-01-01

    PURPOSE: To describe the thickness of the combined ganglion cell and inner plexiform layers (GC-IPL) and the peripapillary retinal nerve fibre layer (RNFL) in patients with OPA1 c.983A>G or c.2708_2711delTTAG autosomal-dominant optic atrophy (ADOA). METHODS: The study included 20 individuals with c...

  10. A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene

    DEFF Research Database (Denmark)

    Højlund, Kurt; Hansen, Torben; Lajer, Maria;

    2004-01-01

    revealed a missense mutation (Arg1174Gln) in the tyrosine kinase domain of the insulin receptor gene that cosegregated with the disease phenotype (logarithm of odds [LOD] score 3.21). In conclusion, we report a novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia. The findings demonstrate the...

  11. White Matter Abnormalities Track Disease Progression in PSEN1 Autosomal Dominant Alzheimer's Disease.

    Science.gov (United States)

    Sánchez-Valle, Raquel; Monté, Gemma C; Sala-Llonch, Roser; Bosch, Beatriz; Fortea, Juan; Lladó, Albert; Antonell, Anna; Balasa, Mircea; Bargalló, Nuria; Molinuevo, José Luis

    2016-02-20

    PSEN1 mutations are the most frequent cause of autosomal dominant Alzheimer's disease (ADAD), and show nearly full penetrance. There is presently increasing interest in the study of biomarkers that track disease progression in order to test therapeutic interventions in ADAD. We used white mater (WM) volumetric characteristics and diffusion tensor imaging (DTI) metrics to investigate correlations with the normalized time to expected symptoms onset (relative age ratio) and group differences in a cohort of 36 subjects from PSEN1 ADAD families: 22 mutation carriers, 10 symptomatic (SMC) and 12 asymptomatic (AMC), and 14 non-carriers (NC). Subjects underwent a 3T MRI. WM morphometric data and DTI metrics were analyzed. We found that PSEN1 MC showed significant negative correlation between fractional anisotropy (FA) and the relative age ratio in the genus and body of corpus callosum and corona radiate (p PSEN1 ADAD from the early phases of the disease; thus DTI metrics might be useful to monitor the disease progression. However, the lack of significant alterations at the preclinical stages suggests that these indexes might not be good candidates for early markers of the disease. PMID:26923015

  12. CT of liver cysts in patients with autosomal dominant polycystic kidney disease

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study was to illustrate the CT appearances of liver cysts in patients with autosomal dominant polycystic kidney disease (ADPKD). Material and methods: Contrast-enhanced CT images of 24 patients with ADPKD were retrospectively evaluated for the presence, number, size and distribution of liver cysts. An attempt was made to categorize these cysts into peribiliary cysts (located adjacent to larger portal triads or in the hepatic hilum) and intrahepatic cysts (within the liver parenchyma but not in contact with larger portal triads). When it was not possible to definitely categorize the cysts into either type, the cysts were labeled as indeterminate. Results: Liver cysts were seen in 13 (54%) patients. Intrahepatic cysts were seen in 12 patients, and were mainly peripheral in location with sizes ranging from less than 10 mm to 8 cm. Peribiliary cysts were seen in all 13 patients and were usually less than 10 mm in size. These cysts were seen as discrete cysts (8 patients), a string of cysts (10 patients), or as a tubular structure paralleling the portal vessels, mimicking biliary dilatation (11 patients). Twelve patients also showed indeterminate cysts which defied definite categorization into either type; two common causes of confusion included large (more than 10 mm) discrete cysts in the hilar region and the presence of a vessel adjacent to peripheral cysts. Conclusion: Liver cysts in patients with ADPKD show a wide variety of appearances of CT. Familiarity with these findings is essential to avoid confusion with other abnormalities. (orig.)

  13. A mutation in COL4A2 causes autosomal dominant porencephaly with cataracts.

    Science.gov (United States)

    Ha, Thuong T; Sadleir, Lynette G; Mandelstam, Simone A; Paterson, Sarah J; Scheffer, Ingrid E; Gecz, Jozef; Corbett, Mark A

    2016-04-01

    Mutations in COL4A1 are well described and result in brain abnormalities manifesting with severe neurological deficits including cerebral palsy, intellectual disability, and focal epilepsy. Families with mutations in COL4A2 are now emerging with a similar phenotype. We describe a family with an autosomal dominant disorder comprising porencephaly, focal epilepsy, and lens opacities, which was negative for mutations in COL4A1. Using whole exome sequencing of three affected individuals from three generations, we identified a rare variant in COL4A2. This COL4A2 (c.2399G>A, p.G800E, CCDS41907.1) variant was predicted to be damaging by multiple bioinformatics tools and affects an invariable glycine residue that is essential for the formation of collagen IV heterotrimers. The cataracts identified in this family expand the phenotypic spectrum associated with mutations in COL4A2 and highlight the increasing overlap with phenotypes associated with COL4A1 mutations. © 2015 Wiley Periodicals, Inc. PMID:26708157

  14. Spinal cord magnetic resonance imaging in autosomal dominant hereditary spastic paraplegia

    International Nuclear Information System (INIS)

    Hereditary spastic paraplegia (HSP) is a genetically heterogeneous group of neurodegenerative disorders characterized by progressive lower extremity weakness and spasticity. HSP pathology involves axonal degeneration that is most pronounced in the terminal segments of the longest descending (pyramidal) and ascending (dorsal columns) tracts. In this study, we compared spinal cord magnetic resonance imaging (MRI) in 13 HSP patients with four different types of autosomal dominant hereditary spastic paraplegia (SPG3A, SPG4, SPG6, and SPG8) with age-matched control subjects. The cross-section area of HSP subjects at cervical level C2 was 59.42±12.57 mm2 and at thoracic level T9 was 28.58±5.25 mm2. Both of these values were less than in the healthy controls (p2 at C2, 21.40±2.4 mm2 at T9) than in subjects with SPG3 and SPG4 (66.0±8.94 mm2 at C2, p2 at T9, p<0.001). These observations indicate that spinal cord atrophy is a common finding in the four genetic types of HSP. Spinal cord atrophy was more severe in SPG6 and SPG8 HSP subjects than in other types of HSP we studied. This may suggest a different disease mechanism with more prominent axonal degeneration in these two types of HSP when compared with HSP due to spastin and atlastin mutations. (orig.)

  15. Identification of a rhodopsin gene mutation in a large family with autosomal dominant retinitis pigmentosa.

    Science.gov (United States)

    Yu, Xinping; Shi, Wei; Cheng, Lulu; Wang, Yanfang; Chen, Ding; Hu, Xuting; Xu, Jinling; Xu, Limin; Wu, Yaming; Qu, Jia; Gu, Feng

    2016-01-01

    Retinitis pigmentosa (RP) is a genetically highly heterogeneous retinal disease and one of the leading causes of blindness in the world. Next-generation sequencing technology has enormous potential for determining the genetic etiology of RP. We sought to identify the underlying genetic defect in a 35-year-old male from an autosomal-dominant RP family with 14 affected individuals. By capturing next-generation sequencing (CNGS) of 144 genes associated with retinal diseases, we identified eight novel DNA variants; however, none of them cosegregated for all the members of the family. Further analysis of the CNGS data led to identification of a recurrent missense mutation (c.403C > T, p.R135W) in the rhodopsin (RHO) gene, which cosegregated with all affected individuals in the family and was not observed in any of the unaffected family members. The p.R135W mutation has a reference single nucleotide polymorphism (SNP) ID (rs104893775), and it appears to be responsible for the disease in this large family. This study highlights the importance of examining NGS data with reference SNP IDs. Thus, our study is important for data analysis of NGS-based clinical genetic diagnoses. PMID:26794436

  16. Cyst growth, polycystins, and primary cilia in autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Lee, Seung Hun; Somlo, Stefan

    2014-06-01

    The primary cilium of renal epithelia acts as a transducer of extracellular stimuli. Polycystin (PC)1 is the protein encoded by the PKD1 gene that is responsible for the most common and severe form of autosomal dominant polycystic kidney disease (ADPKD). PC1 forms a complex with PC2 via their respective carboxy-terminal tails. Both proteins are expressed in the primary cilia. Mutations in either gene affect the normal architecture of renal tubules, giving rise to ADPKD. PC1 has been proposed as a receptor that modulates calcium signals via the PC2 channel protein. The effect of PC1 dosage has been described as the rate-limiting modulator of cystic disease. Reduced levels of PC1 or disruption of the balance in PC1/PC2 level can lead to the clinical features of ADPKD, without complete inactivation. Recent data show that ADPKD resulting from inactivation of polycystins can be markedly slowed if structurally intact cilia are also disrupted at the same time. Despite the fact that no single model or mechanism from these has been able to describe exclusively the pathogenesis of cystic kidney disease, these findings suggest the existence of a novel cilia-dependent, cyst-promoting pathway that is normally repressed by polycystin function. The results enable us to rethink our current understanding of genetics and cilia signaling pathways of ADPKD. PMID:26877954

  17. Determinants of renal volume in autosomal-dominant polycystic kidney disease.

    Science.gov (United States)

    Grantham, J J; Cook, L T; Torres, V E; Bost, J E; Chapman, A B; Harris, P C; Guay-Woodford, L M; Bae, K T

    2008-01-01

    The Consortium of Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) recently showed that renal enlargement in autosomal-dominant polycystic kidney disease mimicked exponential growth. We determined the effects of cyst initiation rate, total number, and growth rate on the time-dependent change of total cyst volume (TCV). Mathematical models with equations integrating cyst surface area, volume, and an invariant growth rate constant were used to compute the time-dependent change in volume of solitary and multiple cysts. Multiple expanding cysts increased TCV in an exponential-like pattern even when individual cysts formed at different rates or exhibited different but constant growth rates. TCV depended on the rate of cyst initiation and on the total number of cysts; however, the compounding effect of exponential-like growth was the most powerful determinant of long-term cyst expansion. Extrapolation of TCV data plots for individual subjects back to an age of 18 predicted TCV values within an established range. We conclude that cysts started early in life were the main contributor to eventual TCV while their growth rate primarily determined renal size; although the rate of formation and the ultimate number of cysts also contributed. The good fit between the exponential models and the extrapolated CRISP data indicates that the TCV growth rate is a defining trait for individual patients and may be used as a prognostic marker. PMID:17960141

  18. Autosomal dominant polycystic kidney disease: new treatment options and how to test their efficacy.

    Science.gov (United States)

    Wüthrich, Rudolf P; Serra, Andreas L; Kistler, Andreas D

    2009-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) represents a slowly progressing cystic kidney disorder which evolves into end-stage renal disease in the majority of patients. Currently, there are no established treatments to retard the progression of the disease, but several promising therapeutic options are being tested in ongoing clinical trials. An inherent dilemma for the investigation of therapies in ADPKD is the dissociation of the early onset and constant rate of cyst growth from the delayed but accelerated loss of renal function. In order to prevent the latter, one needs to act on the former, i.e. current belief by experts in the field is that (1) retardation of cyst growth will ultimately improve the loss of glomerular filtration rate, and (2) cyst volume is an ideal surrogate parameter for outcome in early ADPKD. The present review will discuss the utility and the techniques for kidney and cyst volume measurements to assess disease progression in ADPKD, and summarizes ongoing clinical trials testing novel therapeutic options. PMID:19887826

  19. Comparison of US, CT, and MR for imaging of autosomal dominant polycystic kidney disease

    International Nuclear Information System (INIS)

    Fifty subjects with strong family histories of autosomal dominant polycystic kidney disease (ADPKD) were examined with US, CT, and MR imaging to compare their ability to aid in the diagnosis of ADPKD, assess the degree of disease involvement in the kidneys, liver, and pancreas quantity size of involved organs; and detect complications of ADPKD. Twenty-seven subjects (54%) were positive for ADPKD, 20 (40%) were negative, and three (6%) were suspected to have the disease. In 92% of cases all modalities agreed completely on the number of renal cysts. Contrast material-enhanced CT was more sensitive for detection of small cysts than was US or unenhanced CT. In subjects with ADPKD, unenhanced CT showed renal calculi in 52% of kidneys, while no calculi were demonstrated with US or MR imaging. Complex or hemorrhagic cysts were detected in every subject with MR imaging, in 61% with Ct, and never with US. Acutely hemorrhagic cysts were identified on MR images; subsequent aspiration of these cysts produced symptomatic relief of flank pain. No modality demonstrated infected cysts

  20. A novel GJA8 mutation (p.V44A causing autosomal dominant congenital cataract.

    Directory of Open Access Journals (Sweden)

    Yanan Zhu

    Full Text Available To examine the mechanism by which a novel connexin 50 (Cx50 mutation, Cx50 V44A, in a Chinese family causes suture-sparing autosomal dominant congenital nuclear cataracts.Family history and clinical data were recorded and direct gene sequencing was used to identify the disease-causing mutation. The Cx50 gene was cloned from a human lens cDNA library. Connexin protein distributions were assessed by fluorescence microscopy. Hemichannel functions were analyzed by dye uptake assay. Formation of functional channels was assessed by dye transfer experiments.Direct sequencing of the candidate GJA8 gene revealed a novel c.131T>C transition in exon 2, which cosegregated with the disease in the family and resulted in the substitution of a valine residue with alanine at codon 44 (p. V44A in the extracellular loop 1 of the Cx50 protein. Both Cx50 and Cx50V44A formed functional gap junctions, as shown by the neurobiotin transfer assay. However, unlike wild-type Cx50, Cx50V44A was unable to form open hemichannels in dye uptake experiments.This work identified a unique congenital cataract in the Chinese population, caused by the novel mutation Cx50V44A, and it showed that the V44A mutation specifically impairs the gating of the hemichannels but not the gap junction channels. The dysfunctional hemichannels resulted in the development of human congenital cataracts.

  1. Changes in the plasma proteome at asymptomatic and symptomatic stages of autosomal dominant Alzheimer's disease.

    Science.gov (United States)

    Muenchhoff, Julia; Poljak, Anne; Thalamuthu, Anbupalam; Gupta, Veer B; Chatterjee, Pratishtha; Raftery, Mark; Masters, Colin L; Morris, John C; Bateman, Randall J; Fagan, Anne M; Martins, Ralph N; Sachdev, Perminder S

    2016-01-01

    The autosomal dominant form of Alzheimer's disease (ADAD) is far less prevalent than late onset Alzheimer's disease (LOAD), but enables well-informed prospective studies, since symptom onset is near certain and age of onset is predictable. Our aim was to discover plasma proteins associated with early AD pathology by investigating plasma protein changes at the asymptomatic and symptomatic stages of ADAD. Eighty-one proteins were compared across asymptomatic mutation carriers (aMC, n = 15), symptomatic mutation carriers (sMC, n = 8) and related noncarriers (NC, n = 12). Proteins were also tested for associations with cognitive measures, brain amyloid deposition and glucose metabolism. Fewer changes were observed at the asymptomatic than symptomatic stage with seven and 16 proteins altered significantly in aMC and sMC, respectively. This included complement components C3, C5, C6, apolipoproteins A-I, A-IV, C-I and M, histidine-rich glycoprotein, heparin cofactor II and attractin, which are involved in inflammation, lipid metabolism and vascular health. Proteins involved in lipid metabolism differed only at the symptomatic stage, whereas changes in inflammation and vascular health were evident at asymptomatic and symptomatic stages. Due to increasing evidence supporting the usefulness of ADAD as a model for LOAD, these proteins warrant further investigation into their potential association with early stages of LOAD. PMID:27381087

  2. A mutation in a skin-specific isoform of SMARCAD1 causes autosomal-dominant adermatoglyphia.

    Science.gov (United States)

    Nousbeck, Janna; Burger, Bettina; Fuchs-Telem, Dana; Pavlovsky, Mor; Fenig, Shlomit; Sarig, Ofer; Itin, Peter; Sprecher, Eli

    2011-08-12

    Monogenic disorders offer unique opportunities for researchers to shed light upon fundamental physiological processes in humans. We investigated a large family affected with autosomal-dominant adermatoglyphia (absence of fingerprints) also known as the "immigration delay disease." Using linkage and haplotype analyses, we mapped the disease phenotype to 4q22. One of the genes located in this interval is SMARCAD1, a member of the SNF subfamily of the helicase protein superfamily. We demonstrated the existence of a short isoform of SMARCAD1 exclusively expressed in the skin. Sequencing of all SMARCAD1 coding and noncoding exons revealed a heterozygous transversion predicted to disrupt a conserved donor splice site adjacent to the 3' end of a noncoding exon uniquely present in the skin-specific short isoform of the gene. This mutation segregated with the disease phenotype throughout the entire family. Using a minigene system, we found that this mutation causes aberrant splicing, resulting in decreased stability of the short RNA isoform as predicted by computational analysis and shown by RT-PCR. Taken together, the present findings implicate a skin-specific isoform of SMARCAD1 in the regulation of dermatoglyph development. PMID:21820097

  3. A novel OPA1 mutation in a Chinese family with autosomal dominant optic atrophy

    International Nuclear Information System (INIS)

    Highlights: ► We report the characterization of a four-generation large Chinese family with ADOA. ► We find a new heterozygous mutation c.C1198G in OPA1 gene which may be a novel pathogenic mutation in this pedigree. ► We do not find any mitochondrial DNA mutations associated with optic atrophy. ► Other factors may also contribute to the phenotypic variability of ADOA in this pedigree. -- Abstract: A large four-generation Chinese family with autosomal dominant optic atrophy (ADOA) was investigated in the present study. Eight of the family members were affected in this pedigree. The affected family members exhibited early-onset and progressive visual impairment, resulting in mild to profound loss of visual acuity. The average age-at-onset was 15.9 years. A new heterozygous mutation c.C1198G was identified by sequence analysis of the 12th exon of the OPA1 gene. This mutation resulted in a proline to alanine substitution at codon 400, which was located in an evolutionarily conserved region. This missense mutation in the GTPase domain was supposed to result in a loss of function for the encoded protein and act through a dominant negative effect. No other mutations associated with optic atrophy were found in our present study. The c.C1198G heterozygous mutation in the OPA1 gene may be a novel key pathogenic mutation in this pedigree with ADOA. Furthermore, additional nuclear modifier genes, environmental factors, and psychological factors may also contribute to the phenotypic variability of ADOA in this pedigree.

  4. A novel OPA1 mutation in a Chinese family with autosomal dominant optic atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Juanjuan; Yuan, Yimin; Lin, Bing; Feng, Hao; Li, Yan [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou 325027, Zhejiang (China); Dai, Xianning; Zhou, Huihui [Attardi Institute of Mitochondrial Biomedicine and Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou 325035, Zhejiang (China); Dong, Xujie [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou 325027, Zhejiang (China); Liu, Xiao-Ling, E-mail: lxl@mail.eye.ac.cn [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou 325027, Zhejiang (China); Guan, Min-Xin, E-mail: min-xin.guan@cchmc.org [Attardi Institute of Mitochondrial Biomedicine and Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou 325035, Zhejiang (China); Institute of Genetics, Zhejiang University, Hangzhou, Zhejiang 310012 (China); Division of Human Genetics, Cincinnati Children' s Hospital Medical Center, OH 45229 (United States)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer We report the characterization of a four-generation large Chinese family with ADOA. Black-Right-Pointing-Pointer We find a new heterozygous mutation c.C1198G in OPA1 gene which may be a novel pathogenic mutation in this pedigree. Black-Right-Pointing-Pointer We do not find any mitochondrial DNA mutations associated with optic atrophy. Black-Right-Pointing-Pointer Other factors may also contribute to the phenotypic variability of ADOA in this pedigree. -- Abstract: A large four-generation Chinese family with autosomal dominant optic atrophy (ADOA) was investigated in the present study. Eight of the family members were affected in this pedigree. The affected family members exhibited early-onset and progressive visual impairment, resulting in mild to profound loss of visual acuity. The average age-at-onset was 15.9 years. A new heterozygous mutation c.C1198G was identified by sequence analysis of the 12th exon of the OPA1 gene. This mutation resulted in a proline to alanine substitution at codon 400, which was located in an evolutionarily conserved region. This missense mutation in the GTPase domain was supposed to result in a loss of function for the encoded protein and act through a dominant negative effect. No other mutations associated with optic atrophy were found in our present study. The c.C1198G heterozygous mutation in the OPA1 gene may be a novel key pathogenic mutation in this pedigree with ADOA. Furthermore, additional nuclear modifier genes, environmental factors, and psychological factors may also contribute to the phenotypic variability of ADOA in this pedigree.

  5. Brain acetylcholinesterase activity is markedly reduced in dominantly-inherited olivopontocerebellar atrophy.

    OpenAIRE

    Kish, S J; Schut, L; Simmons, J.; Gilbert, J.; Chang, L. J.; Rebbetoy, M

    1988-01-01

    The activity was measured of the acetylcholine catabolising enzyme acetylcholinesterase (AChE) in brain after necropsy of seven patients from one established pedigree with dominantly-inherited olivopontocerebellar atrophy (OPCA), a cerebellar ataxia disorder in which neuropathological changes are assumed to be primarily restricted to cerebellum, lower brain stem and spinal cord. Mean AChE activity was significantly reduced in cerebral (-51% to 65%) and cerebellar (-47%) cortex with a less sev...

  6. Screening for Unruptured Intracranial Aneurysms in Autosomal Dominant Polycystic Kidney Disease: A Survey of 420 Nephrologists

    Science.gov (United States)

    Flahault, Adrien; Trystram, Denis; Fouchard, Marie; Knebelmann, Bertrand; Nataf, François; Joly, Dominique

    2016-01-01

    Background Despite a high prevalence of intracranial aneurysm (ICA) in autosomal dominant polycystic kidney disease (ADPKD), rupture events are rare. The current recommendations for ICA screening are based on expert opinions and studies with low levels of evidence. Objectives The aim of our study was to describe the attitudes of practicing nephrologists in Europe towards screening for ICA using magnetic resonance angiography (MRA). Methods We conducted a web-based survey among 1315 European French-speaking nephrologists and nephrology residents. An anonymous, electronic questionnaire including 24 independent questions related to ICA screening modalities, indications and participant profiles was sent by email between September and December 2014. Four hundred and twenty nephrologists (mostly from France) participated, including 31 nephrology residents; the response rate was 32%. Results Systematic screening for ICA was advocated by 28% of the nephrologists. A family history of ICA rupture, sudden death, stroke and migraine were consensual indications for screening (> 90% of the panel). In other clinical situations largely not covered by the recommendations (pregnancy, nephrectomy, kidney transplantation, cardiac or hepatic surgery, uncontrolled hypertension, lack of familial ADPKD history, at-risk activity, tobacco use), the attitudes towards screening were highly divergent. ICA screening was influenced by nephrologists experience with ADPKD and by their practice setting. The majority of participants (57%) would not repeat a normal ICA screening. Only a few participants (22%) knew that non-contrast MRA was the reference diagnostic tool for ICA screening, whereas most participants thought that contrast enhancement was necessary to screen for ICA. The results from the nephrology residents were analyzed separately and yielded similar results. Conclusion This practice survey revealed that most nephrologists follow the current recommendations for the initial screening of

  7. Spinal cord magnetic resonance imaging in autosomal dominant hereditary spastic paraplegia

    Energy Technology Data Exchange (ETDEWEB)

    Hedera, P. [University of Michigan, Department of Neurology, Ann Arbor, MI (United States); Vanderbilt University, Department of Neurology, Nashville, TN (United States); Eldevik, O.P.; Maly, P. [University of Michigan, Department of Radiology, Ann Arbor, MI (United States); Rainier, S. [University of Michigan, Department of Neurology, Ann Arbor, MI (United States); Fink, J.K. [University of Michigan, Department of Neurology, Ann Arbor, MI (United States); Ann Arbor Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center, Ann Arbor, MI (United States)

    2005-10-01

    Hereditary spastic paraplegia (HSP) is a genetically heterogeneous group of neurodegenerative disorders characterized by progressive lower extremity weakness and spasticity. HSP pathology involves axonal degeneration that is most pronounced in the terminal segments of the longest descending (pyramidal) and ascending (dorsal columns) tracts. In this study, we compared spinal cord magnetic resonance imaging (MRI) in 13 HSP patients with four different types of autosomal dominant hereditary spastic paraplegia (SPG3A, SPG4, SPG6, and SPG8) with age-matched control subjects. The cross-section area of HSP subjects at cervical level C2 was 59.42{+-}12.57 mm{sup 2} and at thoracic level T9 was 28.58{+-}5.25 mm{sup 2}. Both of these values were less than in the healthy controls (p<0.001). The degree of cord atrophy was more prominent in patients with SPG6 and SPG8 who had signs of severe cord atrophy (47.60{+-}6.58 mm{sup 2} at C2, 21.40{+-}2.4 mm{sup 2} at T9) than in subjects with SPG3 and SPG4 (66.0{+-}8.94 mm{sup 2} at C2, p<0.02; 31.75{+-}2.76 mm{sup 2} at T9, p<0.001). These observations indicate that spinal cord atrophy is a common finding in the four genetic types of HSP. Spinal cord atrophy was more severe in SPG6 and SPG8 HSP subjects than in other types of HSP we studied. This may suggest a different disease mechanism with more prominent axonal degeneration in these two types of HSP when compared with HSP due to spastin and atlastin mutations. (orig.)

  8. A novel retinal oscillation mechanism in an autosomal dominant photoreceptor degeneration mouse model

    Directory of Open Access Journals (Sweden)

    Hung-Ya eTu

    2016-01-01

    Full Text Available It has been shown in rd1 and rd10 models of photoreceptor degeneration (PD that inner retinal neurons display spontaneous and rhythmic activities. Furthermore, the rhythmic activity has been shown to require the gap junction protein connexin 36, which is likely located in AII amacrine cells (AII-ACs. In the present study, an autosomal dominant PD model called rhoΔCTA, whose rods overexpress a C-terminally truncated mutant rhodopsin and degenerate with a rate similar to that of rd1, was used to investigate the generality and mechanisms of heightened inner retinal activity following PD. To fluorescently identify cholinergic starburst amacrine cells (SACs, the rhoΔCTA mouse was introduced into a combined ChAT-IRES-Cre and Ai9 background. In this mouse, we observed large amplitude excitatory postsynaptic currents (EPSCs oscillations and non-rhythmic inhibitory postsynaptic currents (IPSCs in both ON- and OFF-SACs. The IPSCs were more noticeable in OFF- than in ON-SACs. Similar to reported retinal ganglion cell (RGC oscillation in rd1 mice, EPSC oscillation was synaptically driven by glutamate and sensitive to blockade of NaV channels and gap junctions. These data suggest that akin to rd1 mice, AII-AC is a prominent oscillator in rhoΔCTA mice. Surprisingly, OFF-SAC but not ON-SAC EPSC oscillation could readily be enhanced by GABAergic blockade. More importantly, weakening the AII-AC gap junction network by activating retinal dopamine receptors abolished oscillations in ON-SACs but not in OFF-SACs. Furthermore, the latter persisted in the presence of flupirtine, an M-type potassium channel activator recently reported to dampen intrinsic AII-AC bursting. These data suggest the existence of a novel oscillation mechanism in mice with PD.

  9. A Novel Retinal Oscillation Mechanism in an Autosomal Dominant Photoreceptor Degeneration Mouse Model.

    Science.gov (United States)

    Tu, Hung-Ya; Chen, Yu-Jiun; McQuiston, Adam R; Chiao, Chuan-Chin; Chen, Ching-Kang

    2015-01-01

    It has been shown in rd1 and rd10 models of photoreceptor degeneration (PD) that inner retinal neurons display spontaneous and rhythmic activities. Furthermore, the rhythmic activity has been shown to require the gap junction protein connexin 36, which is likely located in AII amacrine cells (AII-ACs). In the present study, an autosomal dominant PD model called rhoΔCTA, whose rods overexpress a C-terminally truncated mutant rhodopsin and degenerate with a rate similar to that of rd1, was used to investigate the generality and mechanisms of heightened inner retinal activity following PD. To fluorescently identify cholinergic starburst amacrine cells (SACs), the rhoΔCTA mouse was introduced into a combined ChAT-IRES-Cre and Ai9 background. In this mouse, we observed excitatory postsynaptic current (EPSC) oscillation and non-rhythmic inhibitory postsynaptic current (IPSC) in both ON- and OFF-SACs. The IPSCs were more noticeable in OFF- than in ON-SACs. Similar to reported retinal ganglion cell (RGC) oscillation in rd1 mice, EPSC oscillation was synaptically driven by glutamate and sensitive to blockade of NaV channels and gap junctions. These data suggest that akin to rd1 mice, AII-AC is a prominent oscillator in rhoΔCTA mice. Surprisingly, OFF-SAC but not ON-SAC EPSC oscillation could readily be enhanced by GABAergic blockade. More importantly, weakening the AII-AC gap junction network by activating retinal dopamine receptors abolished oscillations in ON-SACs but not in OFF-SACs. Furthermore, the latter persisted in the presence of flupirtine, an M-type potassium channel activator recently reported to dampen intrinsic AII-AC bursting. These data suggest the existence of a novel oscillation mechanism in mice with PD. PMID:26793064

  10. Clinical Correlates of Mass Effect in Autosomal Dominant Polycystic Kidney Disease.

    Directory of Open Access Journals (Sweden)

    Hyunsuk Kim

    Full Text Available Mass effect from polycystic kidney and liver enlargement can result in significant clinical complications and symptoms in autosomal dominant polycystic kidney disease (ADPKD. In this single-center study, we examined the correlation of height-adjusted total liver volume (htTLV and total kidney volume (htTKV by CT imaging with hepatic complications (n = 461 and abdominal symptoms (n = 253 in patients with ADPKD. "Mass-effect" complications were assessed by review of medical records and abdominal symptoms, by a standardized research questionnaire. Overall, 91.8% of patients had 4 or more liver cysts on CT scans. Polycystic liver disease (PLD was classified as none or mild (htTLV < 1,600 mL/m; moderate (1,600 ≤ htTLV <3,200 mL/m; and severe (htTLV ≥ 3,200 mL/m. The prevalence of moderate and severe PLD in our patient cohort was 11.7% (n = 54/461 and 4.8% (n = 22/461, respectively, with a female predominance in both the moderate (61.1% and severe (95.5% PLD groups. Pressure-related complications such as leg edema (20.4%, ascites (16.6%, and hernia (3.6% were common, and patients with moderate to severe PLD exhibited a 6-fold increased risk (compared to no or mild PLD for these complications in multivariate analysis. Similarly, abdominal symptoms including back pain (58.8%, flank pain (53.1%, abdominal fullness (46.5%, and dyspnea/chest-discomfort (44.3% were very common, and patients with moderate to severe PLD exhibited a 5-fold increased risk for these symptoms. Moderate to severe PLD is a common and clinically important problem in ~16% of patients with ADPKD who may benefit from referral to specialized centers for further management.

  11. [Pathophysiology, epidemiology, clinical presentation, diagnosis and treatment options for autosomal dominant polycystic kidney disease].

    Science.gov (United States)

    Noël, Natacha; Rieu, Philippe

    2015-07-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the leading genetic cause of end-stage renal disease (ESRD) worldwide. Its prevalence is evaluated according to studies and population between 1/1000 and 1/4000 live births and it accounts for 6 to 8% of incident ESRD patients in developed countries. ADPKD is characterized by numerous cysts in both kidneys and various extrarenal manifestations that are detailed in this review. Clinico-radiological and genetic diagnosis are also discussed. Mutations in the PKD1 and PKD2 codifying for polycystin-1 (PC-1) and polycystin-2 (PC-2) are responsible for the 85 and 15% of ADPKD cases, respectively. In primary cilia of normal kidney epithelial cells, PC-1 and PC-2 interact forming a complex involved in flow- and cilia-dependant signalling pathways where intracellular calcium and cAMP play a central role. Alteration of these multiple signal transduction pathways leads to cystogenesis accompanied by dysregulated planar cell polarity, excessive cell proliferation and fluid secretion, and pathogenic interactions of epithelial cells with an abnormal extracellular matrix. The mass effect of expanding cyst is responsible for the decline in glomerular filtration rate that occurs late in the course of the disease. For many decades, the treatment for ADPKD aims to lessen the condition's symptoms, limit kidney damage, and prevent complications. Recently, the development of promising specific treatment raises the hope to slow the growth of cysts and delay the disease. Treatment strategies targeting cAMP signalling such as vasopressin receptor antagonists or somatostatin analogs have been tested successfully in clinical trials with relative safety. Newer treatments supported by preclinical trials will become available in the next future. Recognizing early markers of renal progression (clinical, imaging, and genetic markers) to identify high-risk patients and multidrug approaches with synergistic effects may provide new opportunities

  12. The role of nicotinic acetylcholine receptors in autosomal dominant nocturnal frontal lobe epilepsy.

    Directory of Open Access Journals (Sweden)

    Andrea eBecchetti

    2015-02-01

    Full Text Available Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE is a focal epilepsy with attacks typically arising in the frontal lobe during non rapid eye movement (NREM sleep. It is characterized by clusters of complex and stereotyped hypermotor seizures, frequently accompanied by sudden arousals. Cognitive and psychiatric symptoms may be also observed. Approximately 12% of the ADNFLE families carry mutations on genes coding for subunits of the heteromeric neuronal nicotinic receptors (nAChRs. This is consistent with the widespread expression of these receptors, particularly the α4β2* subtype, in the neocortex and thalamus. However, understanding how mutant nAChRs lead to partial frontal epilepsy is far from being straightforward because of the complexity of the cholinergic regulation in both developing and mature brains. The relation with the sleep-waking cycle must be also explained. We discuss some possible pathogenetic mechanisms in the light of recent advances about the nAChR role in prefrontal regions as well as the studies carried out in murine models of ADNFLE. Functional evidence points to alterations in prefrontal GABA release, and the synaptic unbalance probably arises during the cortical circuit maturation. Although most of the available functional evidence concerns mutations on nAChR subunit genes, other genes have been recently implicated in the disease, such as KCNT1 (coding for a Na+-dependent K+ channel, DEPD5 (Dishevelled, Egl-10 and Pleckstrin Domain-containing protein 5, and CRH (Corticotropin-Releasing Hormone. Overall, the uncertainties about both the etiology and the pathogenesis of ADNFLE point to the current gaps in our knowledge the regulation of neuronal networks in the cerebral cortex.

  13. Hyperaldosteronism and cardiovascular risk in patients with autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Lai, Silvia; Petramala, Luigi; Mastroluca, Daniela; Petraglia, Emanuela; Di Gaeta, Alessandro; Indino, Elena; Panebianco, Valeria; Ciccariello, Mauro; Shahabadi, Hossein H; Galani, Alessandro; Letizia, Claudio; D'Angelo, Anna Rita

    2016-07-01

    Hypertension is commonly associated with autosomal dominant polycystic kidney disease (ADPKD), often discovered before the onset of renal failure, albeit the pathogenetic mechanisms are not well elucidated. Hyperaldosteronism in ADPKD may contribute to the development of insulin resistance and endothelial dysfunction, and progression of cardiorenal disease. The aim of study was to evaluate the prevalence of primary aldosteronism (PA) in ADPKD patients and identify some surrogate biomarkers of cardiovascular risk.We have enrolled 27 hypertensive ADPKD patients with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, evaluating the renin-angiotensin-aldosterone system (RAAS), inflammatory indexes, nutritional status, homocysteine (Hcy), homeostasis model assessment-insulin resistance (HOMA-IR), mineral metabolism, microalbuminuria, and surrogate markers of atherosclerosis [carotid intima media thickness (cIMT), ankle/brachial index (ABI), flow mediated dilation (FMD), renal resistive index (RRI) and left ventricular mass index (LVMI)]. Furthermore, we have carried out the morpho-functional magnetic resonance imaging (MRI) with high-field 3 T Magnetom Avanto.We have divided patients into group A, with normal plasma aldosterone concentration (PAC) and group B with PA, present in 9 (33%) of overall ADPKD patients. Respect to group A, group B showed a significant higher mean value of LVMI, HOMA-IR and Hcy (P = 0.001, P = 0.004, P = 0.018; respectively), and a lower value of FMD and 25-hydroxyvitamin D (25-OH-VitD) (P = 0.037, P = 0.019; respectively) with a higher prevalence of non-dipper pattern at Ambulatory Blood Pressure Monitoring (ABPM) (65% vs 40%, P FMD, and 25-OH-VitD, considered as surrogate markers of atherosclerosis, compared to ADPKD patients with normal PAC values. Our results indicate a higher overall cardiovascular risk in ADPKD patients with inappropriate aldosterone secretion, and a screening for PA in all patients with

  14. Autosomal dominant cerebellar ataxia type III: a review of the phenotypic and genotypic characteristics

    Directory of Open Access Journals (Sweden)

    Fujioka Shinsuke

    2013-01-01

    Full Text Available Abstract Autosomal Dominant Cerebellar Ataxia (ADCA Type III is a type of spinocerebellar ataxia (SCA classically characterized by pure cerebellar ataxia and occasionally by non-cerebellar signs such as pyramidal signs, ophthalmoplegia, and tremor. The onset of symptoms typically occurs in adulthood; however, a minority of patients develop clinical features in adolescence. The incidence of ADCA Type III is unknown. ADCA Type III consists of six subtypes, SCA5, SCA6, SCA11, SCA26, SCA30, and SCA31. The subtype SCA6 is the most common. These subtypes are associated with four causative genes and two loci. The severity of symptoms and age of onset can vary between each SCA subtype and even between families with the same subtype. SCA5 and SCA11 are caused by specific gene mutations such as missense, inframe deletions, and frameshift insertions or deletions. SCA6 is caused by trinucleotide CAG repeat expansions encoding large uninterrupted glutamine tracts. SCA31 is caused by repeat expansions that fall outside of the protein-coding region of the disease gene. Currently, there are no specific gene mutations associated with SCA26 or SCA30, though there is a confirmed locus for each subtype. This disease is mainly diagnosed via genetic testing; however, differential diagnoses include pure cerebellar ataxia and non-cerebellar features in addition to ataxia. Although not fatal, ADCA Type III may cause dysphagia and falls, which reduce the quality of life of the patients and may in turn shorten the lifespan. The therapy for ADCA Type III is supportive and includes occupational and speech modalities. There is no cure for ADCA Type III, but a number of recent studies have highlighted novel therapies, which bring hope for future curative treatments.

  15. JAK2-STAT3 pathway regulates the expression of complement factor B in autosomal dominant polycystic kidney disease

    Institute of Scientific and Technical Information of China (English)

    周晨晨

    2014-01-01

    Objective To investigate the role of JAK2-STAT3pathway in the expression of complement factor B(CFB)in autosomal dominant polycystic kidney disease(ADP KD).Methods Renal tissue samples of patients with ADPKD after nephrectomy were collected.Normal rena tissue samples as control were taken from patients afte radical nephrectomy.Renal tissue samples of Han:SPRD Cy/+rats(ADPKD model)and wild-type Han:

  16. Urinary Proteomic Biomarkers for Diagnosis and Risk Stratification of Autosomal Dominant Polycystic Kidney Disease: A Multicentric Study

    OpenAIRE

    Kistler, A D; Serra, A.L.; Siwy, J.; Poster, D.; Krauer, F; Torres, V.E.; Mrug, M.; Grantham, J J; Bae, K T; Bost, J.E.; Mullen, W; Wüthrich, R P; Mischak, H.; Chapman, A. B.

    2013-01-01

    Treatment options for autosomal dominant polycystic kidney disease (ADPKD) will likely become available in the near future, hence reliable diagnostic and prognostic biomarkers for the disease are strongly needed. Here, we aimed to define urinary proteomic patterns in ADPKD patients, which aid diagnosis and risk stratification. By capillary electrophoresis online coupled to mass spectrometry (CE-MS), we compared the urinary peptidome of 41 ADPKD patients to 189 healthy controls and identified ...

  17. Targeted exome capture and sequencing identifies novel PRPF31 mutations in autosomal dominant retinitis pigmentosa in Chinese families

    OpenAIRE

    Yang, Liping; Yin, Xiaobei; Wu, Lemeng; Chen, Ningning; Zhang, Huirong; Li, Genlin; Ma, Zhizhong

    2013-01-01

    Objectives To identify disease-causing mutations in two Chinese families with autosomal dominant retinitis pigmentosa (adRP). Design Prospective analysis. Patients Two Chinese adRP families underwent genetic diagnosis. A specific hereditary eye disease enrichment panel (HEDEP) based on targeted exome capture technology was used to collect the protein coding regions of targeted 371 hereditary eye disease genes; high throughput sequencing was done with the Illumina HiSeq 2000 platform. The iden...

  18. Genetic study of autosomal dominant progressive external ophthalmoplegia and familial myasthenia gravis : linkage analysis, candidate gene cloning and mutation detection

    OpenAIRE

    Li, Fang-Yuan

    2001-01-01

    Identification of genes responsible for familial human diseases is a major task of medical genetics. In this process, linkage analysis, candidate gene screening and mutation detection are the three major steps (Paper I-VI). The purpose of this study was to elucidate the genetic backgrounds of autosomal dominant progressive external ophthalmoplegia (adPEO) and familial inyasthenia gravis (FMG). The methods applied in this study for linkage analysis and repeat expansion we...

  19. Clinical characteristics and disease predictors of a large Chinese cohort of patients with autosomal dominant polycystic kidney disease

    OpenAIRE

    Dongping Chen; Yiyi Ma; Xueqi Wang; Shengqiang Yu; Lin Li; Bing Dai; Zhiguo Mao; Lijun Sun; Chenggang Xu; Shu Rong; Mengjun Tang; Hongbo Zhao; Hongchao Liu; Serra, Andreas L.; Nicole Graf

    2014-01-01

    OBJECTIVE: Autosomal dominant polycystic kidney disease (ADPKD) is a relentlessly progressing form of chronic kidney disease for which there is no cure. The aim of this study was to characterize Chinese patients with ADPKD and to identify the factors which predict cyst growth and renal functional deterioration. METHODS: To analyze disease predicting factors we performed a prospective longitudinal observational study in a cohort of 541 Chinese patients with ADPKD and an eGFR ≥ 30 ml/min/1.73 m...

  20. Clinical characteristics and disease predictors of a large Chinese cohort of patients with autosomal dominant polycystic kidney disease

    OpenAIRE

    Chen, Dongping; Ma, Yiyi; Wang, Xueqi; Yu, Shengqiang; Li, Lin; Dai, Bing; Mao, Zhiguo; Sun, Lijun; Xu, Chenggang; Rong, Shu; Tang, Mengjun; Zhao, Hongbo; Liu, Hongchao; Andreas L Serra; Graf, Nicole

    2014-01-01

    OBJECTIVE: Autosomal dominant polycystic kidney disease (ADPKD) is a relentlessly progressing form of chronic kidney disease for which there is no cure. The aim of this study was to characterize Chinese patients with ADPKD and to identify the factors which predict cyst growth and renal functional deterioration. METHODS: To analyze disease predicting factors we performed a prospective longitudinal observational study in a cohort of 541 Chinese patients with ADPKD and an eGFR ≥ 30 ml/min/1.7...

  1. Bidirectional encroachment of collagen into the tunica media in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

    OpenAIRE

    Dong, Hairong; BLAIVAS, MILA; Michael M Wang

    2012-01-01

    Arteries in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are susceptible to smooth muscle loss and fibrosis, but the molecular components underlying these dramatic vascular changes are not well characterized. The purpose of this study was to investigate the distribution of collagen isoforms in the cerebral vessels of North American CADASIL patients with classical NOTCH3 mutations. Expression of type I-VI collagen in brains obtained at au...

  2. Berberine slows cell growth in autosomal dominant polycystic kidney disease cells

    Energy Technology Data Exchange (ETDEWEB)

    Bonon, Anna; Mangolini, Alessandra [Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, 44121 Ferrara (Italy); Pinton, Paolo [Department of Morphology, Surgery and Experimental Medicine, Section of General Pathology, University of Ferrara, 44121 Ferrara (Italy); Senno, Laura del [Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, 44121 Ferrara (Italy); Aguiari, Gianluca, E-mail: dsn@unife.it [Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, 44121 Ferrara (Italy)

    2013-11-22

    Highlights: •Berberine at appropriate doses slows cell proliferation in ADPKD cystic cells. •Reduction of cell growth by berberine occurs by inhibition of ERK and p70-S6 kinase. •Higher doses of berberine cause an overall cytotoxic effect. •Berberine overdose induces apoptotic bodies formation and DNA fragmentation. •Antiproliferative properties of this drug make it a new candidate for ADPKD therapy. -- Abstract: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary monogenic disorder characterized by development and enlargement of kidney cysts that lead to loss of renal function. It is caused by mutations in two genes (PKD1 and PKD2) encoding for polycystin-1 and polycystin-2 proteins which regulate different signals including cAMP, mTOR and EGFR pathways. Abnormal activation of these signals following PC1 or PC2 loss of function causes an increased cell proliferation which is a typical hallmark of this disease. Despite the promising findings obtained in animal models with targeted inhibitors able to reduce cystic cell growth, currently, no specific approved therapy for ADPKD is available. Therefore, the research of new more effective molecules could be crucial for the treatment of this severe pathology. In this regard, we have studied the effect of berberine, an isoquinoline quaternary alkaloid, on cell proliferation and apoptosis in human and mouse ADPKD cystic cell lines. Berberine treatment slows cell proliferation of ADPKD cystic cells in a dose-dependent manner and at high doses (100 μg/mL) it induces cell death in cystic cells as well as in normal kidney tubule cells. However, at 10 μg/mL, berberine reduces cell growth in ADPKD cystic cells only enhancing G{sub 0}/G{sub 1} phase of cell cycle and inhibiting ERK and p70-S6 kinases. Our results indicate that berberine shows a selected antiproliferative activity in cellular models for ADPKD, suggesting that this molecule and similar natural compounds could open new

  3. Two novel mutations of CLCN7 gene in Chinese families with autosomal dominant osteopetrosis (type II).

    Science.gov (United States)

    Zheng, Hui; Shao, Chong; Zheng, Yan; He, Jin-Wei; Fu, Wen-Zhen; Wang, Chun; Zhang, Zhen-Lin

    2016-07-01

    Autosomal dominant osteopetrosis type II (ADO-II) is a heritable bone disorder characterized by osteosclerosis, predominantly involving the spine (vertebral end-plate thickening, or rugger-jersey spine), the pelvis ("bone-within-bone" structures) and the skull base. Chloride channel 7 (CLCN7) has been reported to be the causative gene. In this study, we aimed to identify the pathogenic mutation in four Chinese families with ADO-II. All 25 exons of the CLCN7 gene, including the exon-intron boundaries, were amplified and sequenced directly in four probands from the Chinese families with ADO-II. The mutation site was then identified in other family members and 250 healthy controls. In family 1, a known missense mutation c.296A>G in exon 4 of CLCN7 was identified in the proband, resulting in a tyrosine (UAU) to cysteine (UGU) substitution at p.99 (Y99C); the mutation was also identified in his affected father. In family 2, a novel missense mutation c.865G>C in exon 10 was identified in the proband, resulting in a valine (GUC) to leucine (CUC) substitution at p.289 (V289L); the mutation was also identified in her healthy mother and sister. In family 3, a novel missense mutation c.1625C>T in exon 17 of CLCN7 was identified in the proband, resulting in an alanine (GCG) to valine (GUG) substitution at p.542 (A542V); the mutation was also identified in her father. In family 4, a hot spot, R767W (c.2299C>T, CGG>TGG), in exon 24 was found in the proband which once again proved the susceptibility of the site or the similar genetic background in different races. Moreover, two novel mutations, V289L and A542V, occurred at a highly conserved position, found by a comparison of the protein sequences from eight vertebrates, and were predicted to have a pathogenic effect by PolyPhen-2 software, which showed "probably damaging" with a score of approximately 1. These mutation sites were not identified in 250 healthy controls. Our present findings suggest that the novel missense

  4. Magnetic resonance imaging of posterior pituitary for evaluation of the neurohypophyseal function in idiopathic and autosomal dominant neurohypophyseal diabetes insipidus

    International Nuclear Information System (INIS)

    We investigated the role of MR imaging for evaluation of the functional status of the neurohypophyseal system in both idiopathic central diabetes insipidus (DI) and familial autosomal dominant neurohypophyseal DI. The patients and family with DI were analyzed retrospectively for the presence or absence of posterior pituitary gland hyperintense signal on MR images. A total of 19 adult patients with idiopathic central DI, 7 members of a family with autosomal dominant DI and 20 control subjects were included in the study. Diagnosis of idiopathic DI was based on the presence of central DI in the absence of any alteration that is known to be responsible for DI. The patients were studied retrospectively and the morphology and intensity of the posterior lobe by MR imaging was assessed by blinded reading. In all patients with idiopathic central DI and the affected members of the family, the posterior bright signal was absent while the stalk was normal on MR images. In contrast, normal posterior pituitary bright signal and stalk were found in unaffected members of the family and all control subjects. We conclude that MR imaging of the posterior pituitary lobe can be used to evaluate the functional status of the neurohypophyseal system in idiopathic central DI and familial autosomal dominant DI. (orig.). With 3 figs., 1 tab

  5. Dominant inheritance of field-evolved resistance to Bt corn in Busseolafusca.

    Directory of Open Access Journals (Sweden)

    Pascal Campagne

    Full Text Available Transgenic crops expressing Bacillus thuringiensis (Bt toxins have been adopted worldwide, notably in developing countries. In spite of their success in controlling target pests while allowing a substantial reduction of insecticide use, the sustainable control of these pest populations is threatened by the evolution of resistance. The implementation of the "high dose/refuge" strategy for managing insect resistance in transgenic crops aims at delaying the evolution of resistance to Bt crops in pest populations by promoting survival of susceptible insects. However, a crucial condition for the "high dose/refuge" strategy to be efficient is that the inheritance of resistance should be functionally recessive. Busseolafusca developed high levels of resistance to the Bt toxin Cry 1Ab expressed in Bt corn in South Africa. To test whether the inheritance of B. fusca resistance to the Bt toxin could be considered recessive we performed controlled crosses with this pest and evaluated its survival on Bt and non-Bt corn. Results show that resistance of B. fusca to Bt corn is dominant, which refutes the hypothesis of recessive inheritance. Survival on Bt corn was not lower than on non-Bt corn for both resistant larvae and the F1 progeny from resistant × susceptible parents. Hence, resistance management strategies of B. fusca to Bt corn must address non-recessive resistance.

  6. DNA analysis in inherited cardiomyopathies : Current status and clinical relevance

    NARCIS (Netherlands)

    Van Spaendonck-Zwarts, Karin Y.; Van den Berg, Maarten P.; Van Tintelen, J. Peter

    2008-01-01

    Most hypertrophic cardiomyopathies and a subset of dilated and arrhythmogenic right ventricular cardiomyopathies are familial diseases. They generally show an autosomal dominant pattern of inheritance and have underlying mutations in genes encoding sarcomeric, cytoskeletal, nuclear envelope, and des

  7. External Ocular Manifestations in Autosomal Dominant Dystrophic Epidermolysis Bullosa; a Case Report

    Directory of Open Access Journals (Sweden)

    Manizheh Mahdavi

    2008-11-01

    Full Text Available

    PURPOSE: To present a case of autosomal dominant dystrophic epidermolysis bullosa with symblepharon formation due to eye rubbing. CASE REPORT: A 10-year-old girl suffering from blistering and ulcerative lesions of the trunk and palms and dystrophic nails since childhood was referred to our clinic with a symblepharon connecting the medial portion of the right upper lid to the superonasal quadrant of the cornea. The central cornea in both eyes exhibited mild subepithelial opacification. She had history of eye rubbing due to foreign body sensation in the right eye, resulting in red eye and blister-like conjunctival lesions since three years ago. She had previously undergone surgical symblepharon removal leading to more severe recurrence of the condition. CONCLUSION: Dominant dystrophic epidermolysis bullosa may be accompanied by external ocular manifestations. Protection of the eye from minor trauma such as rubbing may help prevent ocular complications.

  1. Two pedigrees of autosomal dominant atrioventricular canal defect (AVCD): Exclusion from the critical region on 8p

    Energy Technology Data Exchange (ETDEWEB)

    Amati, F.; Mari, A.; Mingarelli, R. [Universita Tor Vergata, Rome (Italy)] [and others

    1995-07-03

    Atrioventricular canal defects (AVCD) constitute the predominant congenital heart defect in Down`s syndrome. For this reason, a candidate gene involved in atrioventricular canal development was previously searched and excluded in dominant pedigrees of AVCD, using linkage analysis of polymorphisms from chromosome 21. Because of the striking association between 8p deletion and AVCD, a search for an AVCD gene was carried out in two pedigrees of individuals with autosomal dominant AVCD using a set of DNA markers of the 8pter{r_arrow}q12 region. These two families include affected individuals and subjects who have transmitted the defect but are not clinically affected. Two-point lod scores were significantly negative for all markers at penetrance levels of 90% and 50%. Multipoint analysis excluded the region covered by the markers LPL-D8S262 and 30 cM to either side of this area. This result corroborates heterogeneity of this heart defect and indicates that the genetic basis of familial AVCD is different from AVCD associated to either trisomy 21 or 8p deletion. 25 refs., 3 figs., 2 tabs.

  2. Localization of a gene (CMT2A) for autosomal dominant Charcot-Marie-Tooth disease type 2 to chromosome 1p and evidence of genetic heterogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Othmane, K.B.; Loprest, L.J.; Wilkinson, K.M. (Duke Univ. Medical Center, Durham, NC (United States)); Middleton, L.T. (Cyprus Institute of Neurology and Genetics, Nicosia (Cyprus)) (and others)

    1993-08-01

    Charcot-Marie-Tooth (CMT) disease type 2 (CMT2) is an inherited peripheral neuropathy characterized by variable age of onset and normal or slightly diminished nerve conduction velocity. CMT2 is pathologically and genetically distinct from CMT type 1 (CMT1). While CMT1 has been shown to be genetically heterogeneous, no chromosomal localization has been established for CMT2. The authors have performed pedigree linkage analysis in six large autosomal dominant CMT2 families and have demonstrated linkage and heterogeneity to a series of microsatellites (D1S160, D1S170, D1S244, D1S228 and D1S199) in the distal region of the short arm of chromosome 1. Significant evidence for heterogeneity was found using admixture analyses and the two-point lod scores. Admixture analyses using the multipoint results for the markers D1S244, D1S228, and D1S199 supported the two-point findings. Three families, DUK662, DUK1241, and 1523 gave posterior probabilities of 1.0, 0.98, and 0.88 of being of the linked type. Multipoint analysis examining the [open quotes]linked[close quotes] families showed that the most favored location for the CMT2A gene is within the interval flanked by D1S244 and D1S228 (odds approximately 70:1 of lying within versus outside that interval). These findings suggest that the CMT2 phenotype is secondary to at least two different genes and demonstrate further heterogeneity in the CMT phenotype.

  3. Autosomal dominant hypercalciuria in a mouse model due to a mutation of the epithelial calcium channel, TRPV5.

    Directory of Open Access Journals (Sweden)

    Nellie Y Loh

    Full Text Available Hypercalciuria is a major cause of nephrolithiasis, and is a common and complex disorder involving genetic and environmental factors. Identification of genetic factors for monogenic forms of hypercalciuria is hampered by the limited availability of large families, and to facilitate such studies, we screened for hypercalciuria in mice from an N-ethyl-N-nitrosourea mutagenesis programme. We identified a mouse with autosomal dominant hypercalciuria (HCALC1. Linkage studies mapped the Hcalc1 locus to a 11.94 Mb region on chromosome 6 containing the transient receptor potential cation channel, subfamily V, members 5 (Trpv5 and 6 (Trpv6 genes. DNA sequence analysis of coding regions, intron-exon boundaries and promoters of Trpv5 and Trpv6 identified a novel T to C transition in codon 682 of TRPV5, mutating a conserved serine to a proline (S682P. Compared to wild-type littermates, heterozygous (Trpv5(682P/+ and homozygous (Trpv5(682P/682P mutant mice had hypercalciuria, polyuria, hyperphosphaturia and a more acidic urine, and ∼10% of males developed tubulointerstitial nephritis. Trpv5(682P/682P mice also had normal plasma parathyroid hormone but increased 1,25-dihydroxyvitamin D(3 concentrations without increased bone resorption, consistent with a renal defect for the hypercalciuria. Expression of the S682P mutation in human embryonic kidney cells revealed that TRPV5-S682P-expressing cells had a lower baseline intracellular calcium concentration than wild-type TRPV5-expressing cells, suggesting an altered calcium permeability. Immunohistological studies revealed a selective decrease in TRPV5-expression from the renal distal convoluted tubules of Trpv5(682P/+ and Trpv5(682P/682P mice consistent with a trafficking defect. In addition, Trpv5(682P/682P mice had a reduction in renal expression of the intracellular calcium-binding protein, calbindin-D(28K, consistent with a specific defect in TRPV5-mediated renal calcium reabsorption. Thus, our findings

  4. Chronic Kidney Pain in Autosomal Dominant Polycystic Kidney Disease : A Case Report of Successful Treatment by Catheter-Based Renal Denervation

    NARCIS (Netherlands)

    Casteleijn, Niek F.; de Jager, Rosa L.; Neeleman, M. Peer; Blankestijn, Peter J.; Gansevoort, Ron T.

    2014-01-01

    Chronic pain is a common concern in patients with autosomal dominant polycystic kidney disease (ADPKD). We report what to our knowledge is the first catheter-based renal denervation procedure in a patient with ADPKD resulting in successful management of chronic pain. The patient was a 43-year-old wo

  5. A novel COCH mutation associated with autosomal dominant nonsyndromic hearing loss disrupts the structural stability of the vWFA2 domain

    NARCIS (Netherlands)

    Cho, H.J.; Park, H.J.; Trexler, M.; Venselaar, H.; Lee, K.Y.; Robertson, N.G.; Baek, J.I.; Kang, B.S.; Morton, C.C.; Vriend, G.; Patthy, L.; Kim, U.K.

    2012-01-01

    Mutations in COCH have been associated with autosomal dominant nonsyndromic hearing loss (DFNA9) and are frequently accompanied by vestibular hypofunction. Here, we report identification of a novel missense mutation, p.F527C, located in the vWFA2 domain in members of a Korean family with late-onset

  6. Mapping of the SCA23 locus involved in autosomal dominant cerebellar ataxia to chromosome region 20p13-12.3

    NARCIS (Netherlands)

    Verbeek, D S; van de Warrenburg, B P; Wesseling, P; Pearson, P L; Kremer, H P; Sinke, R J

    2004-01-01

    We report upon a Dutch autosomal dominant cerebellar ataxia (ADCA) family, clinically characterized by a late-onset (>40 years), slowly progressive, isolated spinocerebellar ataxia (SCA). Neuropathological examination in one affected subject showed neuronal loss in the Purkinje cell layer, dentate n

  7. High-Resolution En Face Images of Microcystic Macular Edema in Patients with Autosomal Dominant Optic Atrophy

    Directory of Open Access Journals (Sweden)

    Kiyoko Gocho

    2013-01-01

    Full Text Available The purpose of this study was to investigate the characteristics of microcystic macular edema (MME determined from the en face images obtained by an adaptive optics (AO fundus camera in patients with autosomal dominant optic atrophy (ADOA and to try to determine the mechanisms underlying the degeneration of the inner retinal cells and RNFL by using the advantage of AO. Six patients from 4 families with ADOA underwent detailed ophthalmic examinations including spectral domain optical coherence tomography (SD-OCT. Mutational screening of all coding and flanking intron sequences of the OPA1 gene was performed by DNA sequencing. SD-OCT showed a severe reduction in the retinal nerve fiber layer (RNFL thickness in all patients. A new splicing defect and two new frameshift mutations with premature termination of the Opa1 protein were identified in three families. A reported nonsense mutation was identified in one family. SD-OCT of one patient showed MME in the inner nuclear layer (INL of the retina. AO images showed microcysts in the en face images of the INL. Our data indicate that AO is a useful method to identify MME in neurodegenerative diseases and may also help determine the mechanisms underlying the degeneration of the inner retinal cells and RNFL.

  8. Papillary renal cell carcinoma with a somatic mutation in MET in a patient with autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Zhang, Wanying; Tan, Adrian Y; Blumenfeld, Jon; Liu, Genyan; Michaeel, Alber; Zhang, Tuo; Robinson, Brian D; Salvatore, Steven P; Kapur, Sandip; Donahue, Stephanie; Bobb, Warren O; Rennert, Hanna

    2016-01-01

    Autosomal-dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 and PKD2 and is characterized by proliferation of renal tubular epithelium and progressive chronic kidney disease. Derangements in similar cellular signaling pathways occur in ADPKD and renal malignancies, although an association of these disorders has not been established. Herein, we present a case of papillary RCC (pRCC) incidentally discovered in a patient with ADPKD following bilateral native nephrectomy during renal transplantation. Whole exome sequencing of the pRCC found a somatic missense mutation in MET proto-oncogene, p.Val1110Ile, not present in kidney cyst epithelium or non-cystic tissue. RNA sequencing demonstrated increased mRNA expression of MET and pathway-related genes, but no significant copy number variation of MET was detected. Genetic analysis of PKD genes from peripheral blood lymphocytes and renal cyst epithelium identified a constitutional PKD1 germline mutation, p.Trp1582Ser, predicted to be pathogenic. Unique somatic mutations in PKD1 were also detected in 80% of the renal cysts analyzed, but not in the pRCC. These results suggest that, in this patient, the pRCC utilized a signaling pathway involving MET that was distinct from the pathogenesis of ADPKD. This is the first report of PKD1 mutations and a somatic mutation of the MET oncogene in a pRCC in ADPKD. PMID:26718059

  9. Ultrastructural appearance of renal and other basement membranes in the Bull terrier model of autosomal dominant hereditary nephritis.

    Science.gov (United States)

    Hood, J C; Savige, J; Seymour, A E; Dowling, J; Martinello, P; Colville, D; Sinclair, R; Naito, I; Jennings, G; Huxtable, C

    2000-08-01

    Bull terrier hereditary nephritis may represent a model for autosomal dominant Alport's syndrome because affected dogs have the typically lamellated glomerular basement membrane (GBM) and father-to-son disease transmission occurs. This study examined the ultrastructural appearance of the renal and extrarenal basement membranes and their composition in affected Bull terriers. Affected stillborn animals and puppies had subepithelial frilling and vacuolation of the GBM. In adult dogs, lamellation was common, and subepithelial frilling and vacuolation were less prominent. Foot-process effacement and mesangial matrix expansion occurred frequently. Basement membranes in the glomeruli, tubules, and Bowman's capsule were significantly thickened and often mineralized. Immunohistochemical examination showed alpha 1(IV) and alpha 2(IV) collagen chains in all renal basement membranes; alpha 3(IV), alpha 4(IV), and alpha 5(IV) chains in the GBM, distal tubular basement membrane, and Bowman's capsule; and the alpha 6(IV) chain in Bowman's capsule. Conversely, the basement membranes from the affected Bull terrier cornea, lens capsule, retina, skin, lung, and muscle had a normal ultrastructural appearance and were not thickened compared with membranes in normal age-matched dogs. The distribution of basement membrane abnormalities in Bull terrier hereditary nephritis may occur because the defective protein is present exclusively or more abundantly in the kidney and is structurally more important in the kidney or because of local intrarenal stresses. PMID:10922317

  10. SDOCT Thickness Measurements of Various Retinal Layers in Patients with Autosomal Dominant Optic Atrophy due to OPA1 Mutations

    Directory of Open Access Journals (Sweden)

    Andrea M. Schild

    2013-01-01

    Full Text Available Purpose. To specify thickness values of various retinal layers on macular spectral domain Optical Coherence Tomography (SDOCT scans in patients with autosomal dominant optic atrophy (ADOA compared to healthy controls. Methods. SDOCT volume scans of 7 patients with ADOA (OPA-1 mutation and 14 healthy controls were quantitatively analyzed using manual grading software. Mean thickness values for the ETDRS grid subfields 5–8 were calculated for the spaces neurosensory retina, retinal nerve fiber layer (RNFL, ganglion cell layer (GCL, a combined space of inner plexiform layer/outer plexiform layer/inner nuclear layer (IPL+INL+OPL, and a combined space of outer nuclear layer/photoreceptor layers (ONL+PL. Results. ADOA patients showed statistically significant lower retinal thickness values than controls (. RNFL ( and GCL thicknesses ( were significantly lower in ADOA patients. There was no difference in IPL+INL+OPL and in ONL+PL thickness. Conclusion. Manual subanalysis of macular SDOCT volume scans allowed detailed subanalysis of various retinal layers. Not only RNFL but also GCL thicknesses are reduced in the macular area of ADOA patients whereas subjacent layers are not involved. Together with clinical findings, macular SDOCT helps to identify patients with suspicion for hereditary optic neuropathy before genetic analysis confirms the diagnosis.

  11. Resting state connectivity and cognitive performance in adults with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

    Science.gov (United States)

    Cullen, Breda; Moreton, Fiona C; Stringer, Michael S; Krishnadas, Rajeev; Kalladka, Dheeraj; López-González, Maria R; Santosh, Celestine; Schwarzbauer, Christian; Muir, Keith W

    2016-05-01

    Cognitive impairment is an inevitable feature of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), affecting executive function, attention and processing speed from an early stage. Impairment is associated with structural markers such as lacunes, but associations with functional connectivity have not yet been reported. Twenty-two adults with genetically-confirmed CADASIL (11 male; aged 49.8 ± 11.2 years) underwent functional magnetic resonance imaging at rest. Intrinsic attentional/executive networks were identified using group independent components analysis. A linear regression model tested voxel-wise associations between cognitive measures and component spatial maps, and Pearson correlations were performed with mean intra-component connectivity z-scores. Two frontoparietal components were associated with cognitive performance. Voxel-wise analyses showed an association between one component cluster and processing speed (left middle temporal gyrus; peak -48, -18, -14; ZE = 5.65, pFWE corr = 0.001). Mean connectivity in both components correlated with processing speed (r = 0.45, p = 0.043; r = 0.56, p = 0.008). Mean connectivity in one component correlated with faster Trailmaking B minus A time (r = -0.77, p cognitive performance and attentional network connectivity in CADASIL. Functional connectivity may be a useful biomarker of cognitive performance in this population. PMID:26929239

  12. Apelin and copeptin: two opposite biomarkers associated with kidney function decline and cyst growth in autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Lacquaniti, Antonio; Chirico, Valeria; Lupica, Rosaria; Buemi, Antoine; Loddo, Saverio; Caccamo, Chiara; Salis, Paola; Bertani, Tullio; Buemi, Michele

    2013-11-01

    Vasopressin (AVP) plays a detrimental role in autosomal dominant polycystic kidney disease (ADPKD). Copeptin represents a measurable substitute for circulating AVP whereas apelin counteracts AVP signaling. The aim of this study was to investigate the predictive value of apelin and copeptin for the progression of ADPKD disease. 52 ADPKD patients were enrolled and followed until the end of the observation period or the primary study endpoint was reached, defined by the combined outcome of decrease of glomerular filtration rate associated with a total renal volume increase. Receiver operating characteristics (ROC) analysis was employed for identifying the progression of renal disease and Kaplan-Meier curves assessed the renal survival. Adjusted risk estimates for progression endpoint and incident renal replacement therapy (RRT) were calculated using Cox proportional hazard regression analysis. ADPKD patients were characterized by lower apelin levels and higher copeptin levels when compared with healthy subjects. These biomarkers were strictly correlated with osmolality and markers of renal function. At ROC analysis, apelin and copeptin showed a very good diagnostic profile in identifying ADPKD progression. After the follow up of 24 months, 33 patients reached the endpoint. Cox proportional hazard regression analysis showed that apelin predicted renal disease progression and incident RRT independently of other potential confounders. Apelin is associated with kidney function decline in ADPKD, suggesting that it may be a new marker to predict kidney outcome. PMID:23973863

  13. Changes in the plasma proteome at asymptomatic and symptomatic stages of autosomal dominant Alzheimer’s disease

    Science.gov (United States)

    Muenchhoff, Julia; Poljak, Anne; Thalamuthu, Anbupalam; Gupta, Veer B.; Chatterjee, Pratishtha; Raftery, Mark; Masters, Colin L.; Morris, John C.; Bateman, Randall J.; Fagan, Anne M.; Martins, Ralph N.; Sachdev, Perminder S.

    2016-01-01

    The autosomal dominant form of Alzheimer’s disease (ADAD) is far less prevalent than late onset Alzheimer’s disease (LOAD), but enables well-informed prospective studies, since symptom onset is near certain and age of onset is predictable. Our aim was to discover plasma proteins associated with early AD pathology by investigating plasma protein changes at the asymptomatic and symptomatic stages of ADAD. Eighty-one proteins were compared across asymptomatic mutation carriers (aMC, n = 15), symptomatic mutation carriers (sMC, n = 8) and related noncarriers (NC, n = 12). Proteins were also tested for associations with cognitive measures, brain amyloid deposition and glucose metabolism. Fewer changes were observed at the asymptomatic than symptomatic stage with seven and 16 proteins altered significantly in aMC and sMC, respectively. This included complement components C3, C5, C6, apolipoproteins A-I, A-IV, C-I and M, histidine-rich glycoprotein, heparin cofactor II and attractin, which are involved in inflammation, lipid metabolism and vascular health. Proteins involved in lipid metabolism differed only at the symptomatic stage, whereas changes in inflammation and vascular health were evident at asymptomatic and symptomatic stages. Due to increasing evidence supporting the usefulness of ADAD as a model for LOAD, these proteins warrant further investigation into their potential association with early stages of LOAD. PMID:27381087

  14. Investigation of the clinical value of assessing renal size on computed tomography in autosomal dominant polycystic kidney disease

    International Nuclear Information System (INIS)

    We examined relationship between serum creatinine concentration (Scr) and renal size on CT scans on 32 occasions in 25 patients with autosomal dominant polycystic kidney disease (ADPKD). As a result, a significant correlation was observed when the Scr was less than 5 mg/dl, as shown by the correlation coefficient (r) and P values of 0.803 and 0.0001, respectively. However, these values changed to 0.482 and 0.0093, respectively when 2 cases with Scr 6.2 and 6.4 mg/dl were included, and further changed to 0.005 and 0.9775 when an additional 4 cases with Scr 7.8, 9.9, 11.1 and 20.1 mg/dl were included. Renal size is therefore thought to be a useful parameter of renal function when the Scr is less than 5 mg/dl in ADPKD, but not when the Scr exceeds 6 mg/dl, and is regarded as useless for predicting the time at which dialysis would be required. (author)

  15. Renal ultrasonographic and computed tomographic appearance, volume, and function of cats with autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Reichle, Jean K; DiBartola, Stephen P; Léveillé, Renée

    2002-01-01

    The purpose of this study was to describe the ultrasonographic (US) and computed tomographic (CT) appearance of autosomal dominant polycystic kidney disease (ADPKD) in cats; to compare renal volume in cats with ADPKD (n = 5; mean age 59 +/- 10 months)) and normal cats (n = 5; mean age 66 +/- 10 months) using 2 imaging modalities, US and CT; and to calculate cyst volume using CT. Glomerular filtration rate (GFR) was determined by 2 methods: 99mTc-diethylene-triaminepentaacetic acid (99mTc-DPTA) scintigraphic uptake and 99-Tc-DTPA plasma clearance. Sonographically, ADPKD affected kidneys were characterized by multiple anechoic to hypoechoic, round to irregularly shaped structures with variation in size. Affected kidneys had indistinct corticomedullary junctions and foci of mineralization. Intravenous (IV) contrast medium administration allowed more definitive identification of cysts with CT, and identification of distortion of renal pelves by cysts. A significant difference (Welch ANOVA, P = 0.05) was detected between the US-estimated renal volumes of normal and affected cats. No statistically significant differences were detected in CT volume (between the normal and affected cats, or between US and CT volume measurements) or the 2 GFR methods. In this group of clinically normal, middle-aged ADPKD cats, renal function was within normal limits and not significantly different than normal. PMID:12175002

  16. Application of Whole Exome Sequencing in Six Families with an Initial Diagnosis of Autosomal Dominant Retinitis Pigmentosa: Lessons Learned.

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    Berta Almoguera

    Full Text Available This study aimed to identify the genetics underlying dominant forms of inherited retinal dystrophies using whole exome sequencing (WES in six families extensively screened for known mutations or genes. Thirty-eight individuals were subjected to WES. Causative variants were searched among single nucleotide variants (SNVs and insertion/deletion variants (indels and whenever no potential candidate emerged, copy number variant (CNV analysis was performed. Variants or regions harboring a candidate variant were prioritized and segregation of the variant with the disease was further assessed using Sanger sequencing in case of SNVs and indels, and quantitative PCR (qPCR for CNVs. SNV and indel analysis led to the identification of a previously reported mutation in PRPH2. Two additional mutations linked to different forms of retinal dystrophies were identified in two families: a known frameshift deletion in RPGR, a gene responsible for X-linked retinitis pigmentosa and p.Ser163Arg in C1QTNF5 associated with Late-Onset Retinal Degeneration. A novel heterozygous deletion spanning the entire region of PRPF31 was also identified in the affected members of a fourth family, which was confirmed with qPCR. This study allowed the identification of the genetic cause of the retinal dystrophy and the establishment of a correct diagnosis in four families, including a large heterozygous deletion in PRPF31, typically considered one of the pitfalls of this method. Since all findings in this study are restricted to known genes, we propose that targeted sequencing using gene-panel is an optimal first approach for the genetic screening and that once known genetic causes are ruled out, WES might be used to uncover new genes involved in inherited retinal dystrophies.

  17. Three families with autosomal dominant nephrogenic diabetes insipidus caused by aquaporin-2 mutations in the C-terminus.

    Science.gov (United States)

    Kuwahara, M; Iwai, K; Ooeda, T; Igarashi, T; Ogawa, E; Katsushima, Y; Shinbo, I; Uchida, S; Terada, Y; Arthus, M F; Lonergan, M; Fujiwara, T M; Bichet, D G; Marumo, F; Sasaki, S

    2001-10-01

    The vasopressin-regulated water channel aquaporin-2 (AQP2) is known to tetramerize in the apical membrane of the renal tubular cells and contributes to urine concentration. We identified three novel mutations, each in a single allele of exon 4 of the AQP2 gene, in three families showing autosomal dominant nephrogenic diabetes insipidus (NDI). These mutations were found in the C-terminus of AQP2: a deletion of G at nucleotide 721 (721 delG), a deletion of 10 nucleotides starting at nucleotide 763 (763-772del), and a deletion of 7 nucleotides starting at nucleotide 812 (812-818del). The wild-type AQP2 is predicted to be a 271-amino acid protein, whereas these mutant genes are predicted to encode proteins that are 330-333 amino acids in length, because of the frameshift mutations. Interestingly, these three mutant AQP2s shared the same C-terminal tail of 61 amino acids. In Xenopus oocytes injected with mutant AQP2 cRNAs, the osmotic water permeability (Pf) was much smaller than that of oocytes with the AQP2 wild-type (14%-17%). Immunoblot analysis of the lysates of the oocytes expressing the mutant AQP2s detected a band at 34 kD, whereas the immunoblot of the plasma-membrane fractions of the oocytes and immunocytochemistry failed to show a significant surface expression, suggesting a defect in trafficking of these mutant proteins. Furthermore, coinjection of wild-type cRNAs with mutant cRNAs markedly decreased the oocyte Pf in parallel with the surface expression of the wild-type AQP2. Immunoprecipitation with antibodies against wild-type and mutant AQP2 indicated the formation of mixed oligomers composed of wild-type and mutant AQP2 monomers. Our results suggest that the trafficking of mutant AQP2 is impaired because of elongation of the C-terminal tail, and the dominant-negative effect is attributed to oligomerization of the wild-type and mutant AQP2s. Segregation of the mutations in the C-terminus of AQP2 with dominant-type NDI underlies the importance of this

  18. De novo post-transplant thrombotic microangiopathy localized only to the graft in autosomal dominant polycystic kidney disease with thrombophilia

    Science.gov (United States)

    Rolla, Davide; Fontana, Iris; Ravetti, Jean Louis; Marsano, Luigina; Bellino, Diego; Panaro, Laura; Ansaldo, Francesca; Mathiasen, Lisa; Storace, Giulia; Trezzi, Matteo

    2015-01-01

    Introduction: Thrombotic microangiopathy (TMA) is a serious complication of renal transplantation and is mostly related to the prothrombotic effect of calcineurin inhibitors (CNIs). A subset of TMA (29%-38%) is localized only to the graft. Case 1: A young woman suffering from autosomal dominant polycystic kidney disease (ADPKD) underwent kidney transplant. After 2 months, she showed slow renal deterioration (serum creatinine from 1.9 to 3.1 mg/dl), without hematological signs of hemolytic-uremic syndrome (HUS); only LDH enzyme transient increase was detected. Renal biopsy showed TMA: temporary withdraw of tacrolimus and plasmapheresis was performed. The renal function recovered (serum creatinine 1.9 mg/dl). From screening for thrombophilia, we found a mutation of the Leiden factor V gene. Case 2: A man affected by ADPKD underwent kidney transplantation, with delay graft function; first biopsy showed acute tubular necrosis, but a second biopsy revealed TMA, while no altered hematological parameters of HUS was detected. We observed only a slight increase of lactate dehydrogenase (LDH) levels. The tacrolimus was halved and plasmapheresis was performed: LDH levels normalized within 10 days and renal function improved (serum creatinine from 9 to 2.9 mg/dl). We found a mutation of the prothrombin gene. Only a renal biopsy clarifies the diagnosis of TMA, but it is necessary to pay attention to light increasing level of LDH. Conclusion: Prothrombotic effect of CNIs and mTOR inhibitor, mutation of genes encoding factor H or I, anticardiolipin antibodies, vascular rejection, cytomegalovirus infection are proposed to trigger TMA; we detected mutations of factor II and Leiden factor V, as facilitating conditions for TMA in patients affected by ADPKD. PMID:26693501

  19. Non-image-forming light driven functions are preserved in a mouse model of autosomal dominant optic atrophy.

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    Georgia Perganta

    Full Text Available Autosomal dominant optic atrophy (ADOA is a slowly progressive optic neuropathy that has been associated with mutations of the OPA1 gene. In patients, the disease primarily affects the retinal ganglion cells (RGCs and causes optic nerve atrophy and visual loss. A subset of RGCs are intrinsically photosensitive, express the photopigment melanopsin and drive non-image-forming (NIF visual functions including light driven circadian and sleep behaviours and the pupil light reflex. Given the RGC pathology in ADOA, disruption of NIF functions might be predicted. Interestingly in ADOA patients the pupil light reflex was preserved, although NIF behavioural outputs were not examined. The B6; C3-Opa1(Q285STOP mouse model of ADOA displays optic nerve abnormalities, RGC dendropathy and functional visual disruption. We performed a comprehensive assessment of light driven NIF functions in this mouse model using wheel running activity monitoring, videotracking and pupillometry. Opa1 mutant mice entrained their activity rhythm to the external light/dark cycle, suppressed their activity in response to acute light exposure at night, generated circadian phase shift responses to 480 nm and 525 nm pulses, demonstrated immobility-defined sleep induction following exposure to a brief light pulse at night and exhibited an intensity dependent pupil light reflex. There were no significant differences in any parameter tested relative to wildtype littermate controls. Furthermore, there was no significant difference in the number of melanopsin-expressing RGCs, cell morphology or melanopsin transcript levels between genotypes. Taken together, these findings suggest the preservation of NIF functions in Opa1 mutants. The results provide support to growing evidence that the melanopsin-expressing RGCs are protected in mitochondrial optic neuropathies.

  20. Urinary proteomic biomarkers for diagnosis and risk stratification of autosomal dominant polycystic kidney disease: a multicentric study.

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    Andreas D Kistler

    Full Text Available Treatment options for autosomal dominant polycystic kidney disease (ADPKD will likely become available in the near future, hence reliable diagnostic and prognostic biomarkers for the disease are strongly needed. Here, we aimed to define urinary proteomic patterns in ADPKD patients, which aid diagnosis and risk stratification. By capillary electrophoresis online coupled to mass spectrometry (CE-MS, we compared the urinary peptidome of 41 ADPKD patients to 189 healthy controls and identified 657 peptides with significantly altered excretion, of which 209 could be sequenced using tandem mass spectrometry. A support-vector-machine based diagnostic biomarker model based on the 142 most consistent peptide markers achieved a diagnostic sensitivity of 84.5% and specificity of 94.2% in an independent validation cohort, consisting of 251 ADPKD patients from five different centers and 86 healthy controls. The proteomic alterations in ADPKD included, but were not limited to markers previously associated with acute kidney injury (AKI. The diagnostic biomarker model was highly specific for ADPKD when tested in a cohort consisting of 481 patients with a variety of renal and extrarenal diseases, including AKI. Similar to ultrasound, sensitivity and specificity of the diagnostic score depended on patient age and genotype. We were furthermore able to identify biomarkers for disease severity and progression. A proteomic severity score was developed to predict height adjusted total kidney volume (htTKV based on proteomic analysis of 134 ADPKD patients and showed a correlation of r = 0.415 (p<0.0001 with htTKV in an independent validation cohort consisting of 158 ADPKD patients. In conclusion, the performance of peptidomic biomarker scores is superior to any other biochemical markers of ADPKD and the proteomic biomarker patterns are a promising tool for prognostic evaluation of ADPKD.

  1. Somatotroph Pituitary Adenoma with Acromegaly and Autosomal Dominant Polycystic Kidney Disease – SSTR5 polymorphism and PKD1 mutation

    Science.gov (United States)

    Syro, Luis V.; Sundsbak, Jamie L.; Scheithauer, Bernd W.; Toledo, Rodrigo A.; Camargo, Mauricio; Heyer, Christina M.; Sekiya, Tomoko; Uribe, Humberto; Escobar, Jorge I.; Vasquez, Martin; Rotondo, Fabio; Toledo, Sergio P. A.; Kovacs, Kalman; Horvath, Eva; Babovic-Vuksanovic, Dusica; Harris, Peter C.

    2014-01-01

    A 39-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) presented with acromegaly and a pituitary macroadenoma. There was a family history of this renal disorder. She had undergone surgery for pituitary adenoma 6 years prior. Physical examination disclosed bitemporal hemianopsia and elevation of both basal growth hormone (GH) 106 ng/mL (normal 0–5) and insulin-like growth factor (IGF-1) 811 ng/mL (normal 48–255) blood levels. A magnetic resonance imaging scan disclosed a 3.0 cm sellar and suprasellar mass with both optic chiasm compression and left cavernous sinus invasion. Histologic, immunohistochemical and ultrastructural studies of the lesion disclosed a sparsely granulated somatotroph adenoma. Standard chromosome analysis on the blood sample showed no abnormality. Sequence analysis of the coding regions of PKD1 and PKD2 employing DNA from both peripheral leukocytes and the tumor revealed the most common PKD1 mutation, 5014_5015delAG. Analysis of the entire SSTR5 gene disclosed the variant c.143C>A (p.L48M, rs4988483) change in the heterozygous state in both blood and tumor, while no pathogenic mutations were noted in the MEN1, AIP, p27Kip1 and SSTR2 genes. To our knowledge, this is the fourth reported case of a GH-producing pituitary adenoma associated with ADPKD, but the first subject to extensive morphological, ultrastructural, cytogenetic and molecular studies. The question arises whether the physical proximity of the PKD1 and SSTR5 genes on chromosome 16 indicates a causal relationship between ADPKD and the somatotroph adenoma. PMID:21744088

  2. Clinical characteristics and disease predictors of a large Chinese cohort of patients with autosomal dominant polycystic kidney disease.

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    Dongping Chen

    Full Text Available OBJECTIVE: Autosomal dominant polycystic kidney disease (ADPKD is a relentlessly progressing form of chronic kidney disease for which there is no cure. The aim of this study was to characterize Chinese patients with ADPKD and to identify the factors which predict cyst growth and renal functional deterioration. METHODS: To analyze disease predicting factors we performed a prospective longitudinal observational study in a cohort of 541 Chinese patients with ADPKD and an eGFR ≥ 30 ml/min/1.73 m(2. Patients were followed clinically and radiologically with sequential abdominal magnetic resonance imaging (MRI. Clinical characteristics and laboratory data were related to changes in estimated glomerular filtration rate (eGFR and total kidney volume (TKV. A linear regression model was developed to analyze the factors which determine eGFR and TKV changes. RESULTS: The age range of this unselected cohort ranged from 4 to 77 years. Median follow-up time was 14.3 ± 10.6 months. Although inter-individual differences in eGFR and TKV were large, there was a consistent link between these two parameters. Baseline log10-transformed TKV and urinary protein/creatinine ratio were identified as the major predictors for a faster eGFR decline and were associated with a higher TKV growth rate. Interestingly, a lower thrombocyte count correlated significantly with lower eGFR (r = 0.222 and higher TKV (r = 0.134. CONCLUSIONS: This large cohort of Chinese patients with ADPKD provides unique epidemiological data for comparison with other cohorts of different ethnicity. In Chinese patients we identified a lower thrombocyte count as a significant predictor of disease progression. These results are important for the design of future clinical trials to retard polycystic kidney disease progression.

  3. Histone deacetylases and autosomal dominant polycystic kidney disease%组蛋白去乙酰化酶与多囊肾病

    Institute of Scientific and Technical Information of China (English)

    薛澄; 梅长林

    2011-01-01

    常染色体显性遗传性多囊肾病(ADPKD)是一种常见的遗传性疾病,发病率约为1/1 000~1/400.ADPKD中基因表达的表观遗传修饰和蛋白质功能的研究已成为最近研究的热点.表观遗传乙酰化修饰中的组蛋白去乙酰化酶(HDACs)参与调节了Pkd1基因的表达,其中HDAC5是液体流动引起的肾上皮细胞钙信号通路作用的靶点;HDAC6在囊泡表皮细胞中过度表达,通过α-tubulin去乙酰化参与调节纤毛形成和表皮生长因子受体(EGFR)的运输,并且通过β-catenin去乙酰化调节Wnt信号通路.HDAC抑制剂既能减少Pkd1基因条件性敲除小鼠囊肿的形成,又能延缓Pkd2基因敲除小鼠肾功能下降,因此抑制HDAC可能成为治疗ADPKD的新靶点.本文主要就ADPKD去乙酰化修饰方面的研究作一综述.%Autosomal dominant polycystic kidney disease(ADPKD) is one of the most frequent inherited kidney diseases, with the incidence rate being 100-250 per 100,000. Epigenetic gene modulation and protein functions have become a focus of study for ADPKD. Evidence generated to-date indicates that one of the epigenetic modifier, histone deacetylases (HDACs), is an important regulator of ADPKD. HDACs have been involved in regulating Pkdl gene expression. HDAC5 is the target of fluid flow-induced calcium signal in kidney epithelial cells. HDAC6 is up-regulated in cystic epithelial cells; they can regulate ciliogenesis and epidermal growth factor receptor (EGFR) transportation through deacetylating α-tubulin and regulate Wnt signaling through deacetylating β-catenin. HDAC inhibitors have been found to reduce cyst formation in Pkdl conditional knockout mice and delay renal function decline in Pkd2 knockout mice, indicating a potential to serve as a new target for ADPKD therapy. This article focuses on the recent progress in research of histone deacetylation in ADPKD.

  4. A de Novo mutation in the coding sequence for neurophysin-II (Pro{sup 24} {yields} Leu) is associated with onset and transmission of autosomal dominant neurohypophyseal diabetes insipidus

    Energy Technology Data Exchange (ETDEWEB)

    Repaske, D.R.; Browning, J.E. [Children`s Hospital Medical Center, Cincinnati, OH (United States)

    1994-08-01

    The molecular basis of autosomal dominant neurohypophyseal diabetes insipidus, a hereditary deficiency of vasopressin, was determined by nucleotide sequence analysis of the arginine vasopressin-neurophysin-II gene. A C{yields}T mutation at nucleotide 1761 was detected in one allele of this gene in each affected individual in three generations of one family. This mutant gene encodes a normal arginine vasopressin peptide, but predicts a substitution of leucine for proline at amino acid 24 of neurophysin-II, the arginine vasopressin carrier protein. This mutation was not detected in 50 control individuals, thus demonstrating that it is not a common silent genetic polymorphism. The disease arose in the second generation of the studied family, and the chromosome 20 carrying this new mutation was identified by polymorphic CA microsatellite haplotype analysis. The first affected individual inherited this chromosome segment from her mother, who had neither the disease nor this mutation in her somatic cell DNA. Third generation individuals who subsequently inherited this mutation were affected. These data demonstrate that this amino acid substitution in neurophysin-II causes this disease. Two possibilities to explain the mechanism by which clinical deficiency of arginine vasopressin develops even in the presence of one normal arginine vasopressin-neurophysin-II allele are discussed. 40 refs., 4 figs., 2 tabs.

  5. Autosomal dominant congenital cataract in a Libyan Jewish family: cosegregation with a reciprocal chromosomal translocation [t(3;5)(p22.3; p15.1)

    OpenAIRE

    Zafer, Emre; Meck, Jeanne; Gerrad, Liora; Pras, Elon; Frydman, Moshe; Reish, Orit; Avni, Isaac; Pras, Eran

    2008-01-01

    Purpose To describe a Jewish family of Libyan ancestry in which autosomal dominant congenital cataract segregates with an apparently balanced reciprocal chromosomal translocation. Methods Detailed family history and clinical data were recorded. Cytogenetic studies were performed on 13 family members. Results Embryonal cataracts cosegregated through three generations with a balanced chromosomal translocation [t(3;5)(p22.3; p15.1)] while the unbalanced translocation product, 46,XY,-5,+der(5)t(3...

  6. Nonmuscle Myosin Heavy Chain IIA Mutations Define a Spectrum of Autosomal Dominant Macrothrombocytopenias: May-Hegglin Anomaly and Fechtner, Sebastian, Epstein, and Alport-Like Syndromes

    OpenAIRE

    Heath, Karen E.; Campos-Barros, Angel; Toren, Amos; Rozenfeld-Granot, Galit; Carlsson, Lena E.; Savige, Judy; Denison, Joyce C.; Gregory, Martin C.; White, James G.; Barker, David F.; Greinacher, Andreas; Epstein, Charles J.; Glucksman, Marc J.; Martignetti, John A.

    2001-01-01

    May-Hegglin anomaly (MHA) and Fechtner (FTNS) and Sebastian (SBS) syndromes are autosomal dominant platelet disorders that share macrothrombocytopenia and characteristic leukocyte inclusions. FTNS has the additional clinical features of nephritis, deafness, and cataracts. Previously, mutations in the nonmuscle myosin heavy chain 9 gene (MYH9), which encodes nonmuscle myosin heavy chain IIA (MYHIIA), were identified in all three disorders. The spectrum of mutations and the genotype-phenotype a...

  7. Increased urinary Angiotensinogen/Creatinine (AGT/Cr) ratio may be associated with reduced renal function in autosomal dominant polycystic kidney disease patients

    OpenAIRE

    Park, Hayne Cho; Kang, Ah-Young; Jang, Joon Young; Kim, Hyunsuk; Han, Miyeun; Oh, Kook-Hwan; Kim, Seung Hyup; Noh, Jung Woo; Cheong, Hae Il; Hwang, Young-Hwan; Ahn, Curie

    2015-01-01

    Background Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary kidney diseases that frequently result in renal failure. In this cross-sectional observational cohort study, we evaluated urinary angiotensinogen (AGT) as a potential biomarker to assess renal function in ADPKD. Methods Urinary AGT was measured in 233 ADPKD patients and its association with estimated glomerular filtration rate (eGFR) and height-adjusted total kidney volume (htTKV) were evaluat...

  8. Relationship of urinary endothelin-1 with estimated glomerular filtration rate in autosomal dominant polycystic kidney disease: a pilot cross-sectional analysis

    OpenAIRE

    Raina, Rupesh; Lou, Linda; Berger, Bruce; Vogt, Beth; Do, Angelique Sao-Mai; Cunningham, Robert; Vasavada, Pauravi; Herrmann, Karin; Dell, Katherine; Simonson, Michael

    2016-01-01

    Background The pathogenesis of progressive renal insufficiency in autosomal dominant polycystic kidney disease (ADPKD) is unclear. Evidence from experimental models of ADPKD suggests that elevated endothelin-1 (ET-1) drives cyst growth, renal fibrosis and loss of renal function, but whether ET-1 is elevated in humans with ADPKD is uncertain. Methods In a cross-sectional study of ADPKD we measured urinary ET-1, a surrogate for ET-1 in kidney cortex, in spot collections corrected for creatinine...

  9. Evaluation of autosomal dominant retinal dystrophy genes in an unaffected cohort suggests rare or private missense variants may often be benign

    OpenAIRE

    Strom, Samuel P.; Gorin, Michael B.

    2013-01-01

    Background Many genes have been reported as harboring autosomal dominant mutations causing retinal dystrophy. As newly available gene panel sequencing and whole exome sequencing will open these genes up to greater scrutiny, we assess the rate of rare coding variation in these genes among unaffected individuals to provide context for variants that will be discovered when clinical subjects are sequenced. Methods Publicly available data from the Exome Variant Project were analyzed, focusing on 3...

  10. Erythropoietin production in renal cell carcinoma and renal cysts in autosomal dominant polycystic kidney disease in a chronic dialysis patient with polycythemia: A case report

    OpenAIRE

    Ito, Keiichi; Asano, Takako; TOMINAGA, SUSUMU; Yoshii, Hidehiko; SAWAZAKI, HARUTAKE; ASANO, TOMOHIKO

    2014-01-01

    In patients undergoing chronic hemodialysis (HD), erythropoietin (EPO) production from the kidney generally decreases and renal anemia develops. Patients without anemia, but with high serum EPO (sEPO) levels are rare among HD patients. The current study presents the case of a 67-year-old female HD patient with autosomal dominant polycystic kidney disease (ADPKD) and renal cell carcinoma (RCC), manifesting polycythemia with elevated sEPO levels. A radical nephrectomy was performed, which dimin...

  11. Intermediate Volume on Computed Tomography Imaging Defines a Fibrotic Compartment that Predicts Glomerular Filtration Rate Decline in Autosomal Dominant Polycystic Kidney Disease Patients

    OpenAIRE

    Caroli, Anna; Antiga, Luca; Conti, Sara; Sonzogni, Aurelio; Fasolini, Giorgio; Ondei, Patrizia; Perico, Norberto; Remuzzi, Giuseppe; Remuzzi, Andrea

    2011-01-01

    Total kidney and cyst volumes have been used to quantify disease progression in autosomal dominant polycystic kidney disease (ADPKD), but a causal relationship with progression to renal failure has not been demonstrated. Advanced image processing recently allowed to quantify extracystic tissue, and to identify an additional tissue component named “intermediate,” appearing hypoenhanced on contrast-enhanced computed tomography (CT). The aim of this study is to provide a histological characteriz...

  12. A COMPLETE SCREEN FOR MUTATIONS OF THE RHODOPSIN GENE IN A PANEL OF CHINESE PATIENTS WITH AUTOSOMAL DOMINANT RETINITIS PIGMENTOSA

    Institute of Scientific and Technical Information of China (English)

    Xiao-li Zhang; Ming Liu; Xiao-hong Meng; Wei-ling Fu; Zheng-qin Yin; Xue Zhang; Jun-fu Huang

    2005-01-01

    Objective To evaluate the prevalence ofrhodopsin (RHO) mutations and the genotype-phenotype relationships in Chinese patients with autosomal dominant retinitis pigmentosa (ADRP) by conformation sensitive gel electrophoresis (CSGE) and direct DNA sequencing.Methods We have screened the five coding exons and splice sites of RHO gene in 27 probands who had no relativity from Chinese ADRP families and 100 normal controls to identify disease-associated mutations, using CSGE and direct DNA sequencing. Family members of some probands with disease-associated mutations were also genotyped to determine whether the RHO mutations segregated with retinitis pigmentosa (RP) in their families.Results Two RHO mutations, Pro347Leu and Pro327 (1-bp del), were identified separately in two families, thus the frequency of RHO mutations among this set of Chinese ADRP families is about 7.4% (2/27). Pro347Leu mutation was found in one ADRP proband as well as three her children who also had RP. She had relatively early onset at about 17 years.The only one child without this mutation had no symptom or sign of RP at age of 34. Pro327 (1-bp del) was identified in a late-onset ADRP patient, who appeared night blindness around 30 years old and in her fifties electroretinogram (ERG) has been flat in both scotopic and photopic phases. Family analysis showed that this mutation also existed in her younger daughter and her elder sister, both of them also had RP. Three other family members were genotypically and phenotypically normal. Neither of the two mutations was detected in 100 normal controls.Conclusions The frequency of RHO mutations in Chinese patients was lower than that in Europe and North America.The phenotype of the patients with Pro347Leu corresponded to type 1 ADRP, with severe rod degeneration and some cone preservation later, while the phenotype of the patients carrying Pro327 (1-bp del) corresponded to type 2 ADRP, with a concomitant loss of rod and cone visual function. CSGE was

  13. Urine-sample-derived human induced pluripotent stem cells as a model to study PCSK9-mediated autosomal dominant hypercholesterolemia

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    Karim Si-Tayeb

    2016-01-01

    Full Text Available Proprotein convertase subtilisin kexin type 9 (PCSK9 is a critical modulator of cholesterol homeostasis. Whereas PCSK9 gain-of-function (GOF mutations are associated with autosomal dominant hypercholesterolemia (ADH and premature atherosclerosis, PCSK9 loss-of-function (LOF mutations have a cardio-protective effect and in some cases can lead to familial hypobetalipoproteinemia (FHBL. However, limitations of the currently available cellular models preclude deciphering the consequences of PCSK9 mutation further. We aimed to validate urine-sample-derived human induced pluripotent stem cells (UhiPSCs as an appropriate tool to model PCSK9-mediated ADH and FHBL. To achieve our goal, urine-sample-derived somatic cells were reprogrammed into hiPSCs by using episomal vectors. UhiPSC were efficiently differentiated into hepatocyte-like cells (HLCs. Compared to control cells, cells originally derived from an individual with ADH (HLC-S127R secreted less PCSK9 in the media (−38.5%; P=0.038 and had a 71% decrease (P<0.001 of low-density lipoprotein (LDL uptake, whereas cells originally derived from an individual with FHBL (HLC-R104C/V114A displayed a strong decrease in PCSK9 secretion (−89.7%; P<0.001 and had a 106% increase (P=0.0104 of LDL uptake. Pravastatin treatment significantly enhanced LDL receptor (LDLR and PCSK9 mRNA gene expression, as well as PCSK9 secretion and LDL uptake in both control and S127R HLCs. Pravastatin treatment of multiple clones led to an average increase of LDL uptake of 2.19±0.77-fold in HLC-S127R compared to 1.38±0.49 fold in control HLCs (P<0.01, in line with the good response to statin treatment of individuals carrying the S127R mutation (mean LDL cholesterol reduction=60.4%, n=5. In conclusion, urine samples provide an attractive and convenient source of somatic cells for reprogramming and hepatocyte differentiation, but also a powerful tool to further decipher PCSK9 mutations and function.

  14. Diagnostic Algorithm in the Management of Acute Febrile Abdomen in Patients with Autosomal Dominant Polycystic Kidney Disease

    Science.gov (United States)

    Neuville, Marie; Hustinx, Roland; Jacques, Jessica; Krzesinski, Jean-Marie

    2016-01-01

    Background Acute febrile abdomen represents a diagnostic challenge in patients with autosomal dominant polycystic kidney disease (ADPKD). Although criteria have been proposed for cyst infection (CyI) and hemorrhage (CyH), there is a lack of comparative assessments. Furthermore, distinguishing cystic from non-cystic complications remains problematic. Design ADPKD patients presenting with abdominal pain and/or fever between 01/2005 and 06/2015 were retrospectively identified in a systematic computerized billing database. CyH was defined as spontaneous intracystic density above 50 Hounsfield units on computed tomography (CT). CyI was definite if confirmed by cyst puncture, and probable if 4 criteria were met: 3-day fever, loin/liver tenderness, C-reactive protein (CRP) plasma levels >50mg/L and no CT evidence for CyH. Other episodes were grouped as inflammation of unknown origin (IUO). Results Among a cohort of 173 ADPKD patients, 101 presented with 205 episodes of abdominal pain (n = 172) and/or fever (n = 33). 20 patients experienced 30 CyH, whereas 16 presented 23 episodes of definite (n = 11) or probable (n = 12) CyI. 35 IUO were observed in 31 patients. Clinically, fever was observed in 7% vs. 100% vs. 66% of CyH, CyI and IUO, respectively. Biologically, CRP cut-off at 70 mg/dl showed 92% sensitivity and 81% specificity in CyI diagnosis. Urine or blood cultures remained sterile in >90% of CyH, but were contributive in 53.4% of CyI and IUO, with a 74.2% prevalence for E. coli. Radiologically, ultrasounds, CT and magnetic resonance diagnosed CyI in 2.6%, 20% and 16.7% of cases, respectively. 18F-FDG positron-emission tomography (PET)/CT was done within a median period of 7 days post antibiotics, and significantly changed patient management in 71.4%. Conclusions This retrospective single-center series underscores the usefulness of clinical–fever–and biological–CRP–parameters, but emphasizes the limitations of bacteriological and radiological investigations

  15. Urine-sample-derived human induced pluripotent stem cells as a model to study PCSK9-mediated autosomal dominant hypercholesterolemia

    Science.gov (United States)

    Si-Tayeb, Karim; Idriss, Salam; Champon, Benoite; Caillaud, Amandine; Pichelin, Matthieu; Arnaud, Lucie; Lemarchand, Patricia; Le May, Cédric; Zibara, Kazem; Cariou, Bertrand

    2016-01-01

    ABSTRACT Proprotein convertase subtilisin kexin type 9 (PCSK9) is a critical modulator of cholesterol homeostasis. Whereas PCSK9 gain-of-function (GOF) mutations are associated with autosomal dominant hypercholesterolemia (ADH) and premature atherosclerosis, PCSK9 loss-of-function (LOF) mutations have a cardio-protective effect and in some cases can lead to familial hypobetalipoproteinemia (FHBL). However, limitations of the currently available cellular models preclude deciphering the consequences of PCSK9 mutation further. We aimed to validate urine-sample-derived human induced pluripotent stem cells (UhiPSCs) as an appropriate tool to model PCSK9-mediated ADH and FHBL. To achieve our goal, urine-sample-derived somatic cells were reprogrammed into hiPSCs by using episomal vectors. UhiPSC were efficiently differentiated into hepatocyte-like cells (HLCs). Compared to control cells, cells originally derived from an individual with ADH (HLC-S127R) secreted less PCSK9 in the media (−38.5%; P=0.038) and had a 71% decrease (P<0.001) of low-density lipoprotein (LDL) uptake, whereas cells originally derived from an individual with FHBL (HLC-R104C/V114A) displayed a strong decrease in PCSK9 secretion (−89.7%; P<0.001) and had a 106% increase (P=0.0104) of LDL uptake. Pravastatin treatment significantly enhanced LDL receptor (LDLR) and PCSK9 mRNA gene expression, as well as PCSK9 secretion and LDL uptake in both control and S127R HLCs. Pravastatin treatment of multiple clones led to an average increase of LDL uptake of 2.19±0.77-fold in HLC-S127R compared to 1.38±0.49 fold in control HLCs (P<0.01), in line with the good response to statin treatment of individuals carrying the S127R mutation (mean LDL cholesterol reduction=60.4%, n=5). In conclusion, urine samples provide an attractive and convenient source of somatic cells for reprogramming and hepatocyte differentiation, but also a powerful tool to further decipher PCSK9 mutations and function. PMID:26586530

  16. Characteristics of Intracranial Aneurysms in the Else Kröner-Fresenius Registry of Autosomal Dominant Polycystic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Hartmut P.H. Neumann

    2012-10-01

    Full Text Available Background: Patients who harbor intracranial aneurysms (IAs run a risk for aneurysm rupture and subsequent subarachnoid hemorrhage which frequently results in permanent deficits or death. Prophylactic treatment of unruptured aneurysms is possible and recommended depending on the size and location of the aneurysm as well as patient age and condition. IAs are major manifestations of autosomal dominant polycystic kidney disease (ADPKD. Current guidelines do not suggest surveillance of IAs in ADPKD except in the setting of family history if IA was known in any relative with ADPKD. Management of IAs in ADPKD is problematic because limited data exist from large studies. Methods: We established the Else Kröner-Fresenius Registry for ADPKD in Germany. Clinical data were assessed for age at diagnosis of IAs, stage of renal insufficiency, and number, location and size of IAs as well as family history of cerebral events. Patients with symptomatic or asymptomatic IAs were included. All patients with ADPKD-related IAs were offered mutation scanning of the susceptibility genes for ADPKD, the PKD1 and PKD2 genes. Results: Of 463 eligible ADPKD patients from the population base of Germany, 32 (7% were found to have IAs, diagnosed at the age of 2–71 years, 19 females and 13 males. Twenty (63% of these 32 patients were symptomatic, whereas IAs were detected in an asymptomatic stage in 12 patients. IAs were multifocal in 12 and unifocal in 20 patients. In 26 patients (81%, IAs were diagnosed before end-stage renal failure. Twenty-five out of 27 unrelated index cases (93% had no IAs or cerebral events documented in their relatives with ADPKD. In 16 unrelated index patients and 3 relatives, we detected germline mutations. The mutations were randomly distributed across the PKD1 gene in 14 and the PKD2 gene in 2 index cases. Questionnaires answered for 320/441 ADPKD patients without IAs revealed that only 45/320 (14% had MR angiography. Conclusion: In ADPKD

  17. PID in Disguise: Molecular Diagnosis of IRAK-4 Deficiency in an Adult Previously Misdiagnosed With Autosomal Dominant Hyper IgE Syndrome.

    Science.gov (United States)

    Frans, Glynis; Moens, Leen; Schrijvers, Rik; Wuyts, Greet; Bouckaert, Bernard; Schaballie, Heidi; Dupont, Lieven; Bossuyt, Xavier; Corveleyn, Anniek; Meyts, Isabelle

    2015-11-01

    Autosomal recessive IL-1R-associated kinase 4 (IRAK-4) deficiency is a rare cause of recurrent pyogenic infections with limited inflammatory responses. We describe an adult female patient with severe lung disease who was phenotypically diagnosed as suffering from autosomal dominant Hyper IgE syndrome (AD HIES) because of recurrent skin infections with Staphylococcus aureus, recurrent pneumonia and elevated serum IgE levels. In contrast to findings in AD HIES patients, no abnormalities were found in the Th17 and circulating follicular helper T cell subsets. A panel-based sequencing approach led to the identification of a homozygous IRAK4 stop mutation (c.877C > T, p.Gln293*). PMID:26472314

  18. Imaging features of tuberous sclerosis complex with autosomal-dominant polycystic kidney disease: a contiguous gene syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Back, Susan J. [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Andronikou, Savvas [University of the Witwatersrand, Radiology Department, Faculty of Health Sciences, Johannesburg (South Africa); Kilborn, Tracy [University of Cape Town, Red Cross War Memorial Children' s Hospital, Cape Town (South Africa); Kaplan, Bernard S. [The Children' s Hospital of Philadelphia, Division of Nephrology, Philadelphia, PA (United States); University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (United States); Darge, Kassa [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (United States)

    2015-03-01

    Genes for tuberous sclerosis complex (TSC) type 2 and autosomal-dominant polycystic kidney disease (ADPKD) type 1 are both encoded over a short segment of chromosome 16. When deletions involve both genes, an entity known as the TSC2/ADPKD1 contiguous gene syndrome, variable phenotypes of TSC and ADPKD are exhibited. This syndrome has not been reviewed in the radiology literature. Unlike renal cysts in TSC, cystic disease in TSC2/ADPKD1 contiguous gene syndrome results in hypertension and renal failure. A radiologist might demonstrate polycystic kidney disease before the patient develops other stigmata of TSC. Conversely, in patients with known TSC, enlarged and polycystic kidneys should signal the possibility of the TSC2/ADPKD1 contiguous gene syndrome and not simply TSC. Distinguishing these diagnoses has implications in prognosis, treatment and genetic counseling. To describe the clinical and imaging findings of tuberous sclerosis complex and polycystic kidney disease in seven pediatric patients. We retrospectively reviewed renal and brain imaging of children and young adults with genetically proven or high clinical suspicion for TSC2/ADPKD1 contiguous gene syndrome. We included seven pediatric patients from two referral institutions. Ages ranged from birth to 21 years over the course of imaging. The mean follow-up period was 9 years 8 months (4 years 6 months to 20 years 6 months). No child progressed to end-stage renal disease during this period. Three patients were initially imaged for stigmata of TSC, three for abdominal distension and one for elevated serum creatinine concentration. All patients developed enlarged, polycystic kidneys. The latest available imaging studies demonstrated that in 12 of the 14 kidneys 50% or more of the parenchyma was ultimately replaced by >15 cysts, resulting in significant cortical thinning. The largest cysts in each kidney ranged from 2.4 cm to 9.3 cm. Echogenic lesions were present in 13 of the 14 kidneys, in keeping with

  19. Imaging features of tuberous sclerosis complex with autosomal-dominant polycystic kidney disease: a contiguous gene syndrome

    International Nuclear Information System (INIS)

    Genes for tuberous sclerosis complex (TSC) type 2 and autosomal-dominant polycystic kidney disease (ADPKD) type 1 are both encoded over a short segment of chromosome 16. When deletions involve both genes, an entity known as the TSC2/ADPKD1 contiguous gene syndrome, variable phenotypes of TSC and ADPKD are exhibited. This syndrome has not been reviewed in the radiology literature. Unlike renal cysts in TSC, cystic disease in TSC2/ADPKD1 contiguous gene syndrome results in hypertension and renal failure. A radiologist might demonstrate polycystic kidney disease before the patient develops other stigmata of TSC. Conversely, in patients with known TSC, enlarged and polycystic kidneys should signal the possibility of the TSC2/ADPKD1 contiguous gene syndrome and not simply TSC. Distinguishing these diagnoses has implications in prognosis, treatment and genetic counseling. To describe the clinical and imaging findings of tuberous sclerosis complex and polycystic kidney disease in seven pediatric patients. We retrospectively reviewed renal and brain imaging of children and young adults with genetically proven or high clinical suspicion for TSC2/ADPKD1 contiguous gene syndrome. We included seven pediatric patients from two referral institutions. Ages ranged from birth to 21 years over the course of imaging. The mean follow-up period was 9 years 8 months (4 years 6 months to 20 years 6 months). No child progressed to end-stage renal disease during this period. Three patients were initially imaged for stigmata of TSC, three for abdominal distension and one for elevated serum creatinine concentration. All patients developed enlarged, polycystic kidneys. The latest available imaging studies demonstrated that in 12 of the 14 kidneys 50% or more of the parenchyma was ultimately replaced by >15 cysts, resulting in significant cortical thinning. The largest cysts in each kidney ranged from 2.4 cm to 9.3 cm. Echogenic lesions were present in 13 of the 14 kidneys, in keeping with

  20. Exome sequencing reveals a heterozygous DLX5 mutation in a Chinese family with autosomal-dominant split-hand/foot malformation

    OpenAIRE

    Wang, Xue; Xin, Qian; Li, Lin; Li, Jiangxia; Zhang, Changwu; Qiu, Rongfang; Qian, Chenmin; Zhao, Hailing; Liu, Yongchao; Shan, Shan; Dang, Jie; Bian, Xianli; Shao, Changshun; Gong, Yaoqin; Liu, Qiji

    2013-01-01

    Split-hand/foot malformation (SHFM) is a congenital limb deformity due to the absence or dysplasia of central rays of the autopod. Six SHFM loci have already been identified. Here we describe a Chinese family with autosomal-dominant SHFM1 that has previously been mapped to 7q21.2-21.3. The two affected family members, mother and son, showed deep median clefts between toes, ectrodactyly and syndactyly; the mother also showed triphalangeal thumbs. Exome sequencing and variant screening of candi...

  1. Post transplant urinary tract infection in Autosomal dominant polycystic kidney disease a perpetual diagnostic dilema - 18-fluorodeoxyglucose - Positron emission computerized tomography - A valuable tool

    International Nuclear Information System (INIS)

    Urinary tract infection (UTI) is the most common infection contracted by renal allograft recipients. In patients of autosomal dominant polycystic kidney disease (ADPKD), cyst infection presents a complex diagnostic and therapeutic challenge especially in the post transplant period. Accurate diagnosis forms the cornerstone in salvaging the graft from potentially catastrophic outcome. We describe a case of xanthogranulomatous pyelonephritis (XPN) in the native kidney in a patient of post transplant ADPKD which presented as frequently relapsing UTI with graft dysfunction where in accurate diagnosis was made possible with the aid of 18-fluorodeoxyglucose (FDG) - Positron emission computerized tomography (PET/CT)

  2. Estimating glomerular filtration rate using the new CKD-EPI equation and other equations in patients with autosomal dominant polycystic kidney disease

    DEFF Research Database (Denmark)

    Orskov, Bjarne; Strandgaard, Svend; Ørskov, Bjarne; Borresen, Malene L; Feldt-Rasmussen, Bo; Østergaard, Ole; Laursen, Inga; Strandgaard, Svend Valdemar

    2010-01-01

    BACKGROUND: No studies have compared the performance of equations for estimating glomerular filtration rate (GFR) in patients with autosomal dominant polycystic kidney disease (ADPKD), where the declining GFR typically is followed for many years or even decades. This was the purpose of the present......-EPI and Cockcroft-Gault equations had an accuracy of 90% whereas the MDRD equation had an accuracy of 83%. This difference of accuracy was especially marked with GFR >60 ml/min/1.73 m(2). CONCLUSION: For estimating GFR in ADPKD patients the MDRD equation with cystatin C incorporated had the best...

  3. Genotype-phenotype correlation for DFNA22: characterization of non-syndromic, autosomal dominant, progressive sensorineural hearing loss due to MYO6 mutations

    DEFF Research Database (Denmark)

    Tranebjærg, Lisbeth; Rendtorff, Nanna D; Topsakal, Vedat;

    2010-01-01

    Clinical and audiological examination was done in 2 Belgian families with autosomal dominant sensorineural hearing loss (SNHL) linked to DFNA22. Nineteen subjects in family 1 had mild to moderate SNHL starting in the third decade. The hearing loss was characterized by a flat audiogram affecting all......Hz. For all hitherto known DFNA22 families the audiological and clinical characteristics were correlated with the molecular data. This study describes the phenotype of 2 Belgian families with SNHL linked to DFNA22, both with a pathogenic change in the deafness gene MYO6. The phenotypes of all hitherto...

  4. Exome sequencing reveals a heterozygous DLX5 mutation in a Chinese family with autosomal-dominant split-hand/foot malformation.

    Science.gov (United States)

    Wang, Xue; Xin, Qian; Li, Lin; Li, Jiangxia; Zhang, Changwu; Qiu, Rongfang; Qian, Chenmin; Zhao, Hailing; Liu, Yongchao; Shan, Shan; Dang, Jie; Bian, Xianli; Shao, Changshun; Gong, Yaoqin; Liu, Qiji

    2014-09-01

    Split-hand/foot malformation (SHFM) is a congenital limb deformity due to the absence or dysplasia of central rays of the autopod. Six SHFM loci have already been identified. Here we describe a Chinese family with autosomal-dominant SHFM1 that has previously been mapped to 7q21.2-21.3. The two affected family members, mother and son, showed deep median clefts between toes, ectrodactyly and syndactyly; the mother also showed triphalangeal thumbs. Exome sequencing and variant screening of candidate genes in the six loci known to be responsible for SHFM revealed a novel heterozygous mutation, c.558G>T (p.(Gln186His)), in distal-less homeobox 5 (DLX5). As DLX5 encodes a transcription factor capable of transactivating MYC, we also tested whether the mutation could affect DLX5 transcription acitivity. Results from luciferase reporter assay revealed that a mutation in DLX5 compromised its transcriptional activity. This is the first report of a mutation in DLX5 leading to autosomal-dominant SHFM1. PMID:24496061

  5. c.G2114A MYH9 mutation (DFNA17) causes non-syndromic autosomal dominant hearing loss in a Brazilian family

    Science.gov (United States)

    Dantas, Vitor G.L.; Lezirovitz, Karina; Yamamoto, Guilherme L.; Moura de Souza, Carolina Fischinger; Ferreira, Simone Gomes; Mingroni-Netto, Regina C.

    2014-01-01

    We studied a family presenting 10 individuals affected by autosomal dominant deafness in all frequencies and three individuals affected by high frequency hearing loss. Genomic scanning using the 50k Affymetrix microarray technology yielded a Lod Score of 2.1 in chromosome 14 and a Lod Score of 1.9 in chromosome 22. Mapping refinement using microsatellites placed the chromosome 14 candidate region between markers D14S288 and D14S276 (8.85 cM) and the chromosome 22 near marker D22S283. Exome sequencing identified two candidate variants to explain hearing loss in chromosome 14 [PTGDR – c.G894A:p.R298R and PTGER2 – c.T247G:p.C83G], and one in chromosome 22 [MYH9, c.G2114A:p.R705H]. Pedigree segregation analysis allowed exclusion of the PTGDR and PTGER2 variants as the cause of deafness. However, the MYH9 variant segregated with the phenotype in all affected members, except the three individuals with different phenotype. This gene has been previously described as mutated in autosomal dominant hereditary hearing loss and corresponds to DFNA17. The mutation identified in our study is the same described in the prior report. Thus, although linkage studies suggested a candidate gene in chromosome 14, we concluded that the mutation in chromosome 22 better explains the hearing loss phenotype in the Brazilian family. PMID:25505834

  6. Cyst number but not the rate of cystic growth is associated with the mutated gene in autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Harris, Peter C; Bae, Kyongtae T; Rossetti, Sandro; Torres, Vicente E; Grantham, Jared J; Chapman, Arlene B; Guay-Woodford, Lisa M; King, Bernard F; Wetzel, Louis H; Baumgarten, Deborah A; Kenney, Philip J; Consugar, Mark; Klahr, Saulo; Bennett, William M; Meyers, Catherine M; Zhang, Qin Jean; Thompson, Paul A; Zhu, Fang; Miller, J Philip

    2006-11-01

    Data from serial renal magnetic resonance imaging of the Consortium of Radiologic Imaging Study of PKD (CRISP) autosomal dominant polycystic kidney disease (PKD) population showed that cystic expansion occurs at a consistent rate per individual, although it is heterogeneous in the population, and that larger kidneys are associated with more rapid disease progression. The significance of gene type to disease progression is analyzed in this study of the CRISP cohort. Gene type was determined in 183 families (219 cases); 156 (85.2%) had PKD1, and 27 (14.8%) had PKD2. PKD1 kidneys were significantly larger, but the rate of cystic growth (PKD1 5.68%/yr; PKD2 4.82%/yr) was not different (P = 0.24). Cyst number increased with age, and more cysts were detected in PKD1 kidneys (P cysts develop earlier, not because they grow faster, implicating the disease gene in cyst initiation but not expansion. These insights will inform the development of targeted therapies in autosomal dominant PKD. PMID:17035604

  7. A gene for autosomal dominant progressive cone dystrophy (CORD5) maps to chromosome 17p12-p13

    Energy Technology Data Exchange (ETDEWEB)

    Balciuniene, J.; Holmgren, G.; Forsman, K. [University Hospital, Umea (Sweden)] [and others

    1995-11-20

    Inherited retinal dystrophy is a common cause of visual impairment. Cone dystrophy affects the cone function and is manifested as progressive loss of the central vision, defective color vision, and photophobia. Linkage was demonstrated between progressive cone dystrophy (CORD5) and genetic markers on chromosome 17p12-p13 in a five-generation family. Multipoint analysis gave a maximum lod score of 7.72 at the marker D17S938. Recombinant haplotypes in the family suggest that the cone dystrophy locus is located in a 25-cM interval between the markers D17S926/D17S849 and D17S804/D17S945. Furthermore, one recombination was detected between the disease locus and a microsatellite marker in the candidate gene RCV1, encoding the retinal protein recoverin. Two additional candidate genes encoding retinal guanylate cyclase (GUC2D) and pigment epithelium-derived factor (PEDF) are located at 17p13.1. Moreover, loci for retinitis pigmentosa and Leber congenital amaurosis have been mapped to the same region. Identification of the cone dystrophy locus may be of importance not only for identifying functional genes in the cone system, but also for identifying genes for other retinal disorders. 34 refs., 3 figs., 2 tabs.

  8. Phenotypic variability in a seven-generation Swedish family segregating autosomal dominant hearing impairment due to a novel EYA4 frameshift mutation

    DEFF Research Database (Denmark)

    Frykholm, Carina; Klar, Joakim; Arnesson, Hanna;

    2015-01-01

    longitudinal deterioration of pure tone average (PTA) once the process of hearing deterioration had started, and no gender, parent-of-origin or family branch differences on PTA could be found. Age at onset varied between the family branches. In summary, this is the ninth published genetically verified DFNA10......Linkage to an interval overlapping the DFNA10 locus on chromosome 6q22-23 was found through genome wide linkage analysis in a seven-generation Swedish family segregating postlingual, autosomal dominant nonsyndromic sensorineural hearing impairment. A novel heterozygous frame-shift mutation (c.579......_580insTACC, p.(Asp194Tyrfs*52)) in EYA4 was identified that truncates the so-called variable region of the protein. The mutation is predicted to result in haploinsufficiency of the EYA4 product. No evidence for dilated cardiomyopathy was found in the family, contrasting to a previous family with a...

  9. Examination of the presynaptic dopaminergic system using positron emission tomography in a family with autosomal dominant parkinsonism and dementia due to pallido-ponto-nigral degeneration (PPNO)

    International Nuclear Information System (INIS)

    We report positron emission tomography (PET) examinations of presynaptic nigrostriatal dopaminergic function in a large family with an autosomal dominant neuro-degenerative disorder characterized pathologically by pallido-ponto-nigral degeneration, and clinically by parkinsonism, dystonia, paresis of conjugate gaze, apraxia of eyelid opening and closing, pyramidal tract dysfunction, and urinary incontinence. Dopaminergic function was studied and quantified with [18F[-L-6-fluorodopa (6 FD) and PET in five affected patients, 13 individuals at-risk, and 15 similarly aged controls. The rate constant Ki (mL/striatum/min) for 6 FD was decreased in all patients. None of the individuals at risk had reduced 6 FD uptake. In fact, three of them had increased values. Repeat scans have revealed a fall in 6 FD uptake in two out of the three with initially high constants. This may reflect a preclinical stage of involvement, but longer observation is necessary. (orig.)

  10. Changes in causes of death and risk of cancer in Danish patients with autosomal dominant polycystic kidney didease and end-stage renal disease

    DEFF Research Database (Denmark)

    Ørskov, Bjarne; Feldt-Rasmussen, Bo Friis; Strandgaard, Svend Valdemar; Sørensen, Vibeke Rømming

    2012-01-01

    Abstract Background. With the improved prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD), causes of death and the risk of cancer might have changed. This was investigated in a Danish population with ADPKD and end-stage renal disease (ESRD) between 1 January 1993 and 31...... December 2008. Methods. Data were retrieved from three Danish national registries and a total of 823 patients were identified of which 431 had died during the study period. The 16 years were divided into two 8-year periods and the causes of death were divided into six categories: cancer, cardiovascular...... (HR) 0.65, P = 0.008] and deaths from cerebrovascular disease decreased by 69% (HR 0.31, P = 0.0003) from the first to the second time period. There were no significant changes between the time periods in death from cancer, infection, other or unknown. From the first to the second 8-year interval, the...

  11. [18F-FDG PET/CT diagnosis of liver cyst infection in a patient with autosomal dominant polycystic kidney disease and fever of unknown origin].

    Science.gov (United States)

    Banzo, J; Ubieto, M A; Gil, D; Prats, E; Razola, P; Tardín, L; Andrés, A; Rambalde, E F; Ayala, S M; Cáncer, L; Velilla, J

    2013-01-01

    The diagnosis, localization and treatment of infected cysts in the kidney or liver of patients with autosomal dominant polycystic kidney disease (ADPKD) remain a clinical challenge. We report the findings of (18)F-FDG PET-CT in an ADPKD diagnosed patient who required renal transplantation five years before and in his follow up presented repeated episodes of bacteriemia without known focus on radiological tests performed. The (18)F-FDG PET-CT scan showed numerous hypermetabolic images with focal or ring-shaped morphology related to the content and the wall of some hepatic cysts. The increased metabolic activity was localized on segments VI and VII. We proceeded to drainage of one cyst in segment VI, removing 110 cc of purulent fluid which grew E. Coli BLEE. The (18)F-FDG PET/CT scan should be included in the diagnostic algorithm for detecting infected liver cysts in patients with ADPKD and fever of unknown origin. PMID:23153986

  12. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, genetic homogeneity, and mapping of the locus within a 2-cM interval

    Energy Technology Data Exchange (ETDEWEB)

    Ducros, A.; Alamowitch, S.; Nagy, T. [INSERM U25, Paris (France)] [and others

    1996-01-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently identified autosomal dominant cerebral arteriopathy characterized by the recurrence of subcortical infarcts leading to dementia. A genetic linkage analysis conducted in two large families recently allowed us to map the affected gene on chromosome 19 in a 12-cM interval bracketed by D19S221 and D19S215. In the present study, these first 2 families and 13 additional ones, including a total of 199 potentially informative meiosis, have been genotyped with eight polymorphic markers located between D19S221 and D19S215. All families were linked to chromosome 19. The highest combined lod score (Z{sub max} = 37.24 at {theta} = .01) was obtained with marker D19S841, a new CA{sub n} microsatellite marker that we isolated from chromosome 19 cosmids. The recombinant events observed within these families were used to refine the genetic mapping of CADASIL within a 2-cM interval that is now bracketed by D19S226 and D19S199 on 19p13.1. These data strongly suggest the genetic homogeneity of this recently identified condition and establish the value of its clinical and neuroimaging diagnostic criteria. Besides their importance for the ongoing positional cloning of the CADASIL gene, these data help to refine the genetic mapping of CADASIL relative to familial hemiplegic migraine and hereditary paroxysmal cerebellar ataxia, conditions that we both mapped within the same chromosome 19 region. 35 refs., 5 figs., 2 tabs.

  13. Examination of the presynaptic dopaminergic system using positron emission tomography in a family with autosomal dominant parkinsonism and dementia due to pallido-ponto-nigral degeneration (PPNO)

    Energy Technology Data Exchange (ETDEWEB)

    Cordes, M. [Neurodegenerative Disorders Centre, Univ. of British Columbia, Vancouver, BC (Canada)]|[Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany); Wszolek, Z.K. [Neurodegenerative Disorders Centre, Univ. of British Columbia, Vancouver, BC (Canada)]|[Section of Neurology, Univ. of Nebraska Medical Center, Omaha, NE (United States); Pfeiffer, R.F. [Section of Neurology, Univ. of Nebraska Medical Center, Omaha, NE (United States); Calne, D.B. [Neurodegenerative Disorders Centre, Univ. of British Columbia, Vancouver, BC (Canada)

    1993-12-31

    We report positron emission tomography (PET) examinations of presynaptic nigrostriatal dopaminergic function in a large family with an autosomal dominant neuro-degenerative disorder characterized pathologically by pallido-ponto-nigral degeneration, and clinically by parkinsonism, dystonia, paresis of conjugate gaze, apraxia of eyelid opening and closing, pyramidal tract dysfunction, and urinary incontinence. Dopaminergic function was studied and quantified with [{sup 18}F]-L-6-fluorodopa (6 FD) and PET in five affected patients, 13 individuals at-risk, and 15 similarly aged controls. The rate constant K{sub i} (mL/striatum/min) for 6 FD was decreased in all patients. None of the individuals at risk had reduced 6 FD uptake. In fact, three of them had increased values. Repeat scans have revealed a fall in 6 FD uptake in two out of the three with initially high constants. This may reflect a preclinical stage of involvement, but longer observation is necessary. (orig.) [Deutsch] Wir berichten ueber Untersuchungen der praesynaptischen dopaminergen Funktion mit der Positronenemissionstomographie bei einer grossen Familie mit autosomal-dominant vererbtem Parkinsonismus und Demenz. Die Erkrankung ist pathologisch-anatomisch gekennzeichnet durch eine pallido-ponto-nigrale Degeneration. Klinisch bestehen ein Parkinsonismus, Dystonien, eine Apraxie der Augenoeffnung und -schliessung, pyramidale Dysfunktionen und eine Harninkontinenz. Die praesynaptische dopaminerge Funktion wurde untersucht und quantifiziert mittels [{sup 18}F]-L-6-Fluorodopa (6FD) PET bei fuenf erkrankten Patienten, 13 Risikopatienten und 15 Kontrollpersonen vergleichbaren Alters. Die Transportkonstante K{sub i} (ml/Striatum/min) fuer die striatale Aufnahme des Radiotracers war bei allen erkrankten Patienten erniedrigt. Von den 13 Risikopatienten hatte keiner eine reduzierte Aufnahme von 6FD. Drei Risikopatienten zeigten sogar Werte fuer K{sub i}, die oberhalb des Referenzbereiches der Kontrollpersonen lagen

  14. Novel heterozygous C243Y A20/TNFAIP3 gene mutation is responsible for chronic inflammation in autosomal-dominant Behçet's disease

    Science.gov (United States)

    Shigemura, Tomonari; Kaneko, Naoe; Kobayashi, Norimoto; Kobayashi, Keiko; Takeuchi, Yusuke; Nakano, Naoko; Masumoto, Junya; Agematsu, Kazunaga

    2016-01-01

    Objective Although Behçet's disease (BD) is a chronic inflammatory disorder of uncertain aetiology, the existence of familial BD with autosomal-dominant traits suggests that a responsibility gene (or genes) exists. We investigated a Japanese family with a history of BD to search for pathogenic mutations underlying the biological mechanisms of BD. Methods 6 patients over 4 generations who had suffered from frequent oral ulcers, genital ulcers and erythaema nodosum-like lesions in the skin were assessed. Whole-exome sequencing was performed on genomic DNA, and cytokine production was determined from stimulated mononuclear cells. Inflammatory cytokine secretion and Nod2-mediated NF-κB activation were analysed using the transfected cells. Results By whole-exome sequencing, we identified a common heterozygous missense mutation in A20/TNFAIP3, a gene known to regulate NF-κB signalling, for which all affected family members carried a heterozygous C243Y mutation in the ovarian tumour domain. Mononuclear cells obtained from the proband and his mother produced large amounts of interleukin 1β, IL-6 and tumour necrosis factor α (TNF-a) on stimulation as compared with those from normal controls. Although inflammatory cytokine secretion was suppressed by wild-type transfected cells, it was suppressed to a much lesser extent by mutated C243Y A20/TNFAIP3-transfected cells. In addition, impaired suppression of Nod2-mediated NF-κB activation by C243Y A20/TNFAIP3 was observed. Conclusions A C243Y mutation in A20/TNFAIP3 was likely responsible for increased production of human inflammatory cytokines by reduced suppression of NF-κB activation, and may have accounted for the autosomal-dominant Mendelian mode of BD transmission in this family. PMID:27175295

  15. DVL3 Alleles Resulting in a -1 Frameshift of the Last Exon Mediate Autosomal-Dominant Robinow Syndrome.

    Science.gov (United States)

    White, Janson J; Mazzeu, Juliana F; Hoischen, Alexander; Bayram, Yavuz; Withers, Marjorie; Gezdirici, Alper; Kimonis, Virginia; Steehouwer, Marloes; Jhangiani, Shalini N; Muzny, Donna M; Gibbs, Richard A; van Bon, Bregje W M; Sutton, V Reid; Lupski, James R; Brunner, Han G; Carvalho, Claudia M B

    2016-03-01

    Robinow syndrome is a rare congenital disorder characterized by mesomelic limb shortening, genital hypoplasia, and distinctive facial features. Recent reports have identified, in individuals with dominant Robinow syndrome, a specific type of variant characterized by being uniformly located in the penultimate exon of DVL1 and resulting in a -1 frameshift allele with a premature termination codon that escapes nonsense-mediated decay. Here, we studied a cohort of individuals who had been clinically diagnosed with Robinow syndrome but who had not received a molecular diagnosis from variant studies of DVL1, WNT5A, and ROR2. Because of the uniform location of frameshift variants in DVL1-mediated Robinow syndrome and the functional redundancy of DVL1, DVL2, and DVL3, we elected to pursue direct Sanger sequencing of the penultimate exon of DVL1 and its paralogs DVL2 and DVL3 to search for potential disease-associated variants. Remarkably, targeted sequencing identified five unrelated individuals harboring heterozygous, de novo frameshift variants in DVL3, including two splice acceptor mutations and three 1 bp deletions. Similar to the variants observed in DVL1-mediated Robinow syndrome, all variants in DVL3 result in a -1 frameshift, indicating that these highly specific alterations might be a common cause of dominant Robinow syndrome. Here, we review the current knowledge of these peculiar variant alleles in DVL1- and DVL3-mediated Robinow syndrome and further elucidate the phenotypic features present in subjects with DVL1 and DVL3 frameshift mutations. PMID:26924530

  16. Autosomal recessive transmission of a rare KRT74 variant causes hair and nail ectodermal dysplasia: allelism with dominant woolly hair/hypotrichosis.

    Directory of Open Access Journals (Sweden)

    Doroteya Raykova

    Full Text Available Pure hair and nail ectodermal dysplasia (PHNED comprises a heterogeneous group of rare heritable disorders characterized by brittle hair, hypotrichosis, onychodystrophy and micronychia. Autosomal recessive (AR PHNED has previously been associated with mutations in either KRT85 or HOXC13 on chromosome 12p11.1-q14.3. We investigated a consanguineous Pakistani family with AR PHNED linked to the keratin gene cluster on 12p11.1 but without detectable mutations in KRT85 and HOXC13. Whole exome sequencing of affected individuals revealed homozygosity for a rare c.821T>C variant (p.Phe274Ser in the KRT74 gene that segregates AR PHNED in the family. The transition alters the highly conserved Phe274 residue in the coil 1B domain required for long-range dimerization of keratins, suggesting that the mutation compromises the stability of intermediate filaments. Immunohistochemical (IHC analyses confirmed a strong keratin-74 expression in the nail matrix, the nail bed and the hyponychium of mouse distal digits, as well as in normal human hair follicles. Furthermore, hair follicles and epidermis of an affected family member stained negative for Keratin-74 suggesting a loss of function mechanism mediated by the Phe274Ser substitution. Our observations show for the first time that homozygosity for a KRT74 missense variant may be associated with AR PHNED. Heterozygous KRT74 mutations have previously been associated with autosomal dominant woolly hair/hypotrichosis simplex (ADWH. Thus, our findings expand the phenotypic spectrum associated with KRT74 mutations and imply that a subtype of AR PHNED is allelic with ADWH.

  17. Autosomal dominant transmission of a Goldenhar-like syndrome: Description of a family and report of a sporadic case with a de novo 4p16;8q24.11 translocation

    Energy Technology Data Exchange (ETDEWEB)

    Graganm H.N. Jr.; Hixon, H.; Bacino, C.A. [Univ. of Iowa, Iowa City, IA (United States)] [and others

    1994-09-01

    We report vertical transmission of a Goldenhar-like syndrome, including a father and 5 offspring, with male-to-male transmission and variable features that include hearing loss, ear anomalies (microtia, ear tags/pits), branchial cysts, ocular/periocular dermoids, micrognathia and seizures. We also report an individual with an apparently balanced de novo reciprocal translocation with breakpoints at 4p16 and 8q24.11. This individual has unilateral microtia, an epibulbar dermoid cyst, facial asymmetry with a small chin, and seizures. In addition to these features resembling those seen in the family above, she has multiple exostoses, supraventricular tachycardia, hypoglycemia and mild developmental delays. Based on the overlap in physical findings between this family and the individual with the de novo reciprocal translocation, linkage studies on the family were intiated. Preliminary results exclude linkage to HOX 7 at 4p16.1 but not to 8q. The brancho-oto-renal syndrome has previously been localized to 8q11-8q13, but linkage to this region appears unlikely. Although most cases of Goldenhar syndrome appear to be sporadic, there are a few reports of autosomal dominant inheritance (MIM No. 164210). One such family showed vertical transmission of dermoids, ear anomalies, hearing loss, micrognathia and vertebral anomalies, but no branchial cysts. Another family showed sensorineural deafness, preauricular pits, and branchial fistulae, and other families reveal ear anomalies, branchial fistulas, and hearing loss. These latter families appear to lack ocular/periocular dermoids, and appear to be affected by a different disorder (MIM No. 125100). Further clinical delineation of such families, combined with genetic linkage analysis, should help to sort out this heterogeneity.

  18. Dominantly inherited cerebral dysplasia: arachnoid cyst associated with mild mental handicap in a mother and her son.

    OpenAIRE

    Tolmie, J L; Day, R.; Fredericks, B; Galea, P; Moffett, A W

    1997-01-01

    We report a mother and son who each presented in infancy with hypotonia and global developmental delay. Subsequently, in both subjects, mild mental handicap was diagnosed in association with temporal lobe arachnoid cysts. Mendelian inheritance of this phenotype seems likely and macroscopic cerebral dysplasia in general may be underdiagnosed in people with familial, mild mental handicap.

  19. Medical resource utilization and costs associated with autosomal dominant polycystic kidney disease in the USA: a retrospective matched cohort analysis of private insurer data

    Directory of Open Access Journals (Sweden)

    Knight T

    2015-02-01

    Full Text Available Tyler Knight,1 Caroline Schaefer,1 Holly Krasa,2 Dorothee Oberdhan,2 Arlene Chapman,3 Ronald D Perrone4 1Covance Market Access Services Inc., Gaithersburg, MD, 2Otsuka Pharmaceutical Development and Commercialization, Inc., Rockville, MD, 3Emory University, Atlanta, GA, 4Tufts Medical Center and Tufts University School of Medicine, Boston, MA, USA Background: Autosomal dominant polycystic kidney disease (ADPKD results in kidney cyst development and enlargement, resulting in chronic kidney disease (CKD leading to renal failure. This study sought to determine if ADPKD patients in the early stages of CKD contribute to a sizable economic burden for the US health care system. Methods: This was a retrospective, matched cohort study, reviewing medical resource utilization (MRU and costs for adults in a US private-payer claims database with a diagnosis code of ADPKD (ICD-9-CM 753.13. ADPKD patients were matched by age grouping (0–17, 18–34, 35–44, 45–54, 55–64, and 65+ years and sex to controls to understand the burden of ADPKD. Descriptive statistics on 6-month MRU and costs were assessed by CKD stages, dialysis use, or previous renal transplant. Results: The analysis included ADPKD patients in CKD stages 1–5 (n=316 to n=860, dialysis (n=586, and post-transplant (n=615. Mean ages did not differ across CKD stages (range 43–56 years. Men were the majority in the later stages but the minority in the early stages. The proportion of patients with at least one hospitalization increased with CKD stage, (12% to >40% CKD stage 2 to stage 5, dialysis or post-transplant. The majority had at least one hospital outpatient visit and at least one pharmacy claim. Total 6-month per-patient costs were greater among ADPKD patients than in age-matched and sex-matched healthy non-ADPKD controls (P<0.001 for all comparisons. Conclusion: ADPKD patients with normal kidney function are associated with a significant economic burden to the health care system

  20. Relationship of Copeptin, a Surrogate Marker for Arginine Vasopressin, With Change in Total Kidney Volume and GFR Decline in Autosomal Dominant Polycystic Kidney Disease : Results From the CRISP Cohort

    NARCIS (Netherlands)

    Boertien, Wendy E.; Meijer, Esther; Li, Jie; Bost, James E.; Struck, Joachim; Flessner, Michael F.; Gansevoort, Ron T.; Torres, Vicente E.

    2013-01-01

    Background: Experimental studies indicate that arginine vasopressin (AVP) may have deleterious effects in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). However, the significance of AVP in human ADPKD is unclear. Study Design: Longitudinal observational study with 8.5 (IQR

  1. Feasibility of measuring renal blood flow by phase-contrast magnetic resonance imaging in patients with autosomal dominant polycystic kidney disease

    Energy Technology Data Exchange (ETDEWEB)

    Spithoven, E.M.; Meijer, E.; Boertien, W.E.; Gaillard, C.A.J.M.; Jong, P.E. de; Gansevoort, R.T. [University of Groningen, Department of Nephrology, Community and Occupational Medicine, University Medical Center Groningen, PO Box 30.001, RB Groningen (Netherlands); Borns, C.; Kappert, P.; Greuter, M.J.W.; Jagt, E. van der [University of Groningen, Department of Radiology, Community and Occupational Medicine, University Medical Center Groningen, Groningen (Netherlands); Vart, P. [University of Groningen, Department of Health Sciences, Community and Occupational Medicine, University Medical Center Groningen, Groningen (Netherlands)

    2016-03-15

    Renal blood flow (RBF) has been shown to predict disease progression in autosomal dominant polycystic kidney disease (ADPKD). We investigated the feasibility and accuracy of phase-contrast RBF by MRI (RBF{sub MRI}) in ADPKD patients with a wide range of estimated glomerular filtration rate (eGFR) values. First, we validated RBF{sub MRI} measurement using phantoms simulating renal artery hemodynamics. Thereafter, we investigated in a test-set of 21 patients intra- and inter-observer coefficient of variation of RBF{sub MRI}. After validation, we measured RBF{sub MRI} in a cohort of 91 patients and compared the variability explained by characteristics indicative for disease severity for RBF{sub MRI} and RBF measured by continuous hippuran infusion. The correlation in flow measurement using phantoms by phase-contrast MRI was high and fluid collection was high (CCC=0.969). Technical problems that precluded RBF{sub MRI} measurement occurred predominantly in patients with a lower eGFR (34% vs. 16%). In subjects with higher eGFRs, variability in RBF explained by disease characteristics was similar for RBF{sub MRI} compared to RBF{sub Hip,} whereas in subjects with lower eGFRs, this was significantly less for RBF{sub MRI}. Our study shows that RBF can be measured accurately in ADPKD patients by phase-contrast, but this technique may be less feasible in subjects with a lower eGFR. (orig.)

  2. Mutation in the PCSK9 Gene in Omani Arab Subjects with Autosomal Dominant Hypercholesterolemia and its Effect on PCSK9 Protein Structure

    Directory of Open Access Journals (Sweden)

    Khalid Al-Waili

    2013-01-01

    Full Text Available Proprotein convertase subtilisin/kexin type (PCSK9 is a crucial protein in LDL cholesterol (LDL-C metabolism by virtue of its pivotal role in the degradation of the LDL receptor. Mutations in the PCSK9 gene have previously been found to segregate with autosomal dominant familial hypercholesterolemia (ADFH. In this study, DNA sequencing of the 12 exons of the PCSK9 gene has been performed for two patients with a clinical diagnosis of familial hypercholesterolemia where mutation in the LDL-receptor gene hasn't been excluded. One missense mutation was detected in the exon 9 PCSK9 gene in the two ADFH patients. The patients were found to be heterozygote for Ile474Val (SNP rs562556. Using an array of in silico tools, we have investigated the effect of the above mutation on different structural levels of the PCSK9 protein. Although, the mutation has already been reported in the literature for other populations, to the best of our knowledge this is the first report of a mutation in the PCSK9 gene from the Arab population, including the Omani population.

  3. Whole exome sequencing links dental tumor to an autosomal-dominant mutation in ANO5 gene associated with gnathodiaphyseal dysplasia and muscle dystrophies.

    Science.gov (United States)

    Andreeva, T V; Tyazhelova, T V; Rykalina, V N; Gusev, F E; Goltsov, A Yu; Zolotareva, O I; Aliseichik, M P; Borodina, T A; Grigorenko, A P; Reshetov, D A; Ginter, E K; Amelina, S S; Zinchenko, R A; Rogaev, E I

    2016-01-01

    Tumors of the jaws may represent different human disorders and frequently associate with pathologic bone fractures. In this report, we analyzed two affected siblings from a family of Russian origin, with a history of dental tumors of the jaws, in correspondence to original clinical diagnosis of cementoma consistent with gigantiform cementoma (GC, OMIM: 137575). Whole exome sequencing revealed the heterozygous missense mutation c.1067G > A (p.Cys356Tyr) in ANO5 gene in these patients. To date, autosomal-dominant mutations have been described in the ANO5 gene for gnathodiaphyseal dysplasia (GDD, OMIM: 166260), and multiple recessive mutations have been described in the gene for muscle dystrophies (OMIM: 613319, 611307); the same amino acid (Cys) at the position 356 is mutated in GDD. These genetic data and similar clinical phenotypes demonstrate that the GC and GDD likely represent the same type of bone pathology. Our data illustrate the significance of mutations in single amino-acid position for particular bone tissue pathology. Modifying role of genetic variations in another gene on the severity of the monogenic trait pathology is also suggested. Finally, we propose the model explaining the tissue-specific manifestation of clinically distant bone and muscle diseases linked to mutations in one gene. PMID:27216912

  4. Autosomal dominant Marfan-like connective-tissue disorder with aortic dilation and skeletal anomaslies not linked to the Fibrillin genes

    Energy Technology Data Exchange (ETDEWEB)

    Boileau, C.; Coulon, M.; Alexandre, J.-A.; Junien, C. (Laboratorie Central de Biochimie et de Genetique Moleculaire (France)); Jondeau, G.; Delorme, G.; Dubourg, O.; Bourdarias, J.-P. (CHU Ambroise Pare, Boulogne (France)); Babron, M.-C.; Bonaieti-Pellie, C. (INSERM, Chateau de Longchamp, Paris (France)); Sakai, L. (Shriners' Hospital for Crippled Children, Portland, OR (United States)); Melki, J. (Hopital Necker-Enfants Malades, Paris (France))

    1993-07-01

    The authors describe a large family with a connective-tissue disorder that exhibits some of the skeletal and cardiovascular features seen in Marfan syndrome. However, none of the 19 affected individuals displayed ocular abnormalities and therefore did not comply with recognized criteria for this disease. These patients could alternatively be diagnosed as MASS (mitral valve, aorta, skeleton, and skin) phenotype patients or represent a distinct clinical entity, i.e., a new autosomal dominant connective-tissue disorder. The fibrillin genes located on chromosomes 15 and 5 are clearly involved in the classic form of Marfan syndrome and a clinically related disorder (congenital contractural arachnodactyly), respectively. To test whether one of these genes was also implicated in this French family, the authors performed genetic analyses. Blood samples were obtained for 56 family members, and four polymorphic fibrillin gene markers, located on chromosomes 15 (Fib15) and 5 (Fib5), respectively, were tested. Linkage between the disease allele and the markers of these two genes was excluded with lod scores of [minus]11.39 (for Fib15) and [minus]13.34 (for Fib5), at 0 = .001, indicating that the mutation is at a different locus. This phenotype thus represents a new connective-tissue disorder, overlapping but different from classic Marfan syndrome. 33 refs., 1 fig. 2 tabs.

  5. Identification of 13 new mutations in the vasopressin-neurophysin II gene in 17 kindreds with familial autosomal dominant neurohypophyseal diabetes insipidus

    Energy Technology Data Exchange (ETDEWEB)

    Rittig, S.; Siggaard, C.; Pedersen, E.B. [Aahus Univ. Hospital and Faculty of Health Sciences (Denmark)] [and others

    1996-01-01

    Familial neurohypophyseal diabetes insipidus (FNDI) is an autosomal dominant disorder characterized by progressive postnatal deficiency of arginine vasopressin as a result of mutation in the gene that encodes the hormone. To determine the extent of mutations in the coding region that produce the phenotype, we studied members of 17 unrelated kindreds with the disorder. We sequenced all 3 exons of the gene by using a rapid, direct dye-terminator method and found the causative mutation in each kindred. In four kindreds, the mutations were each identical to mutations described in other affected families. In the other 13 kindreds each mutation was unique. There were two missense mutations that altered the cleavage region of the signal peptide, seven missense mutations in exon 2, which codes for the conserved portion of the protein, one nonsense mutation in exon 2, and three nonsense mutations in exon 3. These findings, together with the clinical features of FNDI, suggest that each of the mutations exerts an effect by directing the production of a pre-prohormone that cannot be folded, processed, or degraded properly and eventually destroys vasopressinergic neurons. 63 refs., 5 figs., 6 tabs.

  6. RHO Mutations (p.W126L and p.A346P in Two Japanese Families with Autosomal Dominant Retinitis Pigmentosa

    Directory of Open Access Journals (Sweden)

    Satoshi Katagiri

    2014-01-01

    Full Text Available Purpose. To investigate genetic and clinical features of patients with rhodopsin (RHO mutations in two Japanese families with autosomal dominant retinitis pigmentosa (adRP. Methods. Whole-exome sequence analysis was performed in ten adRP families. Identified RHO mutations for the cosegregation analysis were confirmed by Sanger sequencing. Ophthalmic examinations were performed to evaluate the RP phenotypes. The impact of the RHO mutation on the rhodopsin conformation was examined by molecular modeling analysis. Results. In two adRP families, we identified two RHO mutations (c.377G>T (p.W126L and c.1036G>C (p.A346P, one of which was novel. Complete cosegregation was confirmed for each mutation exhibiting the RP phenotype in both families. Molecular modeling predicted that the novel mutation (p.W126L might impair rhodopsin function by affecting its conformational transition in the light-adapted form. Clinical phenotypes showed that patients with p.W126L exhibited sector RP, whereas patients with p.A346P exhibited classic RP. Conclusions. Our findings demonstrated that the novel mutation (p.W126L may be associated with the phenotype of sector RP. Identification of RHO mutations is a very useful tool for predicting disease severity and providing precise genetic counseling.

  7. SPM analysis of brain perfusion SPECT and F-18 FDG PET in the Korean autosomal dominant nocturnal frontal lobe epilepsy family

    International Nuclear Information System (INIS)

    This study attempted to investigate the specific pattern of brain perfusion and glucose metabolism in the Korean autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) family. Using Tc-99m ECD brain perfusion SPECT. we assessed brain perfusion in 6 patients at interictal period and 5 patients at ictal period. Interictal F-18 FDG PET was performed on 6 affected family members. The scans were statistically analyzed by using statistical parametric mapping (SPM99). The data of the affected family members were compared to those of the control subjects. Interictal F-18 FDG PET SPM group analysis showed decreased glucose metabolism over the left middle and superior frontal gyri and the left central regions including the anterior parietal lobe. There was a less pronounced decrease in glucose uptake in the right anterior superior frontal gyrus. Interictal brain perfusion SPECT SPM group analysis showed similar pattern of decreased perfusion compared to those of interictal F-18 FDG PET. Ictal brain perfusion SPECT SPM group analysis revealed increased perfusion over the left pre-and postcentral gyri and less pronounced increased perfusion in the right postcentral gyrus. lnterictal F -18 PET and brain perfusion SPECT SPM group analysis suggest that major abnormalities of ADNFLE family are in the left frontal lobe. These findings may be helpful to elucidate the pathophysiological mechanism of this rare disease entity

  8. Exome Sequencing Identifies a Missense Variant in EFEMP1 Co-Segregating in a Family with Autosomal Dominant Primary Open-Angle Glaucoma.

    Directory of Open Access Journals (Sweden)

    Donna S Mackay

    Full Text Available Primary open-angle glaucoma (POAG is a clinically important and genetically heterogeneous cause of progressive vision loss as a result of retinal ganglion cell death. Here we have utilized trio-based, whole-exome sequencing to identify the genetic defect underlying an autosomal dominant form of adult-onset POAG segregating in an African-American family. Exome sequencing identified a novel missense variant (c.418C>T, p.Arg140Trp in exon-5 of the gene coding for epidermal growth factor (EGF containing fibulin-like extracellular matrix protein 1 (EFEMP1 that co-segregated with disease in the family. Linkage and haplotype analyses with microsatellite markers indicated that the disease interval overlapped a known POAG locus (GLC1H on chromosome 2p. The p.Arg140Trp substitution was predicted in silico to have damaging effects on protein function and transient expression studies in cultured cells revealed that the Trp140-mutant protein exhibited increased intracellular accumulation compared with wild-type EFEMP1. In situ hybridization of the mouse eye with oligonucleotide probes detected the highest levels of EFEMP1 transcripts in the ciliary body, cornea, inner nuclear layer of the retina, and the optic nerve head. The recent finding that a common variant near EFEMP1 was associated with optic nerve-head morphology supports the possibility that the EFEMP1 variant identified in this POAG family may be pathogenic.

  9. Feasibility of measuring renal blood flow by phase-contrast magnetic resonance imaging in patients with autosomal dominant polycystic kidney disease

    International Nuclear Information System (INIS)

    Renal blood flow (RBF) has been shown to predict disease progression in autosomal dominant polycystic kidney disease (ADPKD). We investigated the feasibility and accuracy of phase-contrast RBF by MRI (RBFMRI) in ADPKD patients with a wide range of estimated glomerular filtration rate (eGFR) values. First, we validated RBFMRI measurement using phantoms simulating renal artery hemodynamics. Thereafter, we investigated in a test-set of 21 patients intra- and inter-observer coefficient of variation of RBFMRI. After validation, we measured RBFMRI in a cohort of 91 patients and compared the variability explained by characteristics indicative for disease severity for RBFMRI and RBF measured by continuous hippuran infusion. The correlation in flow measurement using phantoms by phase-contrast MRI was high and fluid collection was high (CCC=0.969). Technical problems that precluded RBFMRI measurement occurred predominantly in patients with a lower eGFR (34% vs. 16%). In subjects with higher eGFRs, variability in RBF explained by disease characteristics was similar for RBFMRI compared to RBFHip, whereas in subjects with lower eGFRs, this was significantly less for RBFMRI. Our study shows that RBF can be measured accurately in ADPKD patients by phase-contrast, but this technique may be less feasible in subjects with a lower eGFR. (orig.)

  10. Endothelin 1 gene is not a major modifier of chronic kidney disease advancement among the autosomal dominant polycystic kidney disease patients

    Directory of Open Access Journals (Sweden)

    Annapareddy Shiva Nagendra Reddy

    2016-01-01

    Full Text Available Introduction: Autosomal dominant polycystic kidney disease (ADPKD is characterized by the presence of numerous cysts in the kidney and manifest with various renal and extra-renal complications leading to ESRD. Endothelin may contribute to various renal and extra-renal manifestations pointing to genetic and environmental modifying factors that alter the risk of developing chronic kidney disease (CKD in ADPKD. In the present study we investigated six genes coding for endothelin 1 (EDN1 tagging-single nucleotide polymorphisms (tag-SNPs to unravel the EDN1 gene modifier effect for renal disease progression in ADPKD. Materials and Methods: The tag-SNPs were genotyped using FRET-based KASPar method in 108 ADPKD patients and 119 healthy subjects. Cochran-Armitage trend test was used to determine the association between ADPKD and EDN1 tag-SNPs. Multivariate logistic regression analysis was performed to assess the effect of tag-SNPs on CKD progression. The relationship between different CKD stages and hypertension and their interaction Mantel-Haenszel stratified analysis was performed. Results: All loci are polymorphic and followed Hardy-Weinberg equilibrium. Distribution of EDN1 genotypes and haplotypes in control and ADPKD is not statistically significant. Five SNPs covering 3.4 kb forming single LD block, but the LD was not strong between SNPs. The EDN1 genotypes are not contributing to the CKD advancement among the ADPKD patients. Conclusion: These results suggest that the EDN1 gene is not a major modifier of CKD advancement among ADPKD patients.

  11. Three novel and the common Arg677Ter RP1 protein truncating mutations causing autosomal dominant retinitis pigmentosa in a Spanish population

    Directory of Open Access Journals (Sweden)

    Antiñolo Guillermo

    2006-04-01

    Full Text Available Abstract Background Retinitis pigmentosa (RP, a clinically and genetically heterogeneous group of retinal degeneration disorders affecting the photoreceptor cells, is one of the leading causes of genetic blindness. Mutations in the photoreceptor-specific gene RP1 account for 3–10% of cases of autosomal dominant RP (adRP. Most of these mutations are clustered in a 500 bp region of exon 4 of RP1. Methods Denaturing gradient gel electrophoresis (DGGE analysis and direct genomic sequencing were used to evaluate the 5' coding region of exon 4 of the RP1 gene for mutations in 150 unrelated index adRP patients. Ophthalmic and electrophysiological examination of RP patients and relatives according to pre-existing protocols were carried out. Results Three novel disease-causing mutations in RP1 were detected: Q686X, K705fsX712 and K722fsX737, predicting truncated proteins. One novel missense mutation, Thr752Met, was detected in one family but the mutation does not co-segregate in the family, thereby excluding this amino acid variation in the protein as a cause of the disease. We found the Arg677Ter mutation, previously reported in other populations, in two independent families, confirming that this mutation is also present in a Spanish population. Conclusion Most of the mutations reported in the RP1 gene associated with adRP are expected to encode mutant truncated proteins that are approximately one third or half of the size of wild type protein. Patients with mutations in RP1 showed mild RP with variability in phenotype severity. We also observed several cases of non-penetrant mutations.

  12. Cyst Ablation Using a Mixture of N-Butyl Cyanoacrylate and Iodized Oil in Patients with Autosomal Dominant Polycystic Kidney Disease: the Long-Term Results

    Energy Technology Data Exchange (ETDEWEB)

    Kim, See Hyung; Kim, Seung Hyup; Cho, Jeong Yeon [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2009-08-15

    We wanted to assess the long-term results of cyst ablation with using N-butyl cyanoacrylate (NBCA) and iodized oil in patients with autosomal dominant polycystic kidney disease (ADPKD) and symptomatic cysts. Cyst ablation using a mixture of NBCA and iodized oil was performed in 99 cysts from 21 patients who had such symptoms as abdominal distension and pain. The collapse or reaccumulation of the ablated cysts after the procedure was assessed during the follow-up period of 36 to 90 months. The treatment effects, including symptom relief, and the clinical data such as the blood pressure and serum creatinine levels were also assessed, together with the complications. The procedure was technically successful in all 99 cysts from the 21 patients. Any procedure-related significant complications were not detected. Seventy-seven of 99 cysts (78%) were successfully collapsed on the follow-up CT. Twenty-two cysts showed reaccumulation during long-term follow-up period. The clinical symptoms were relieved in 17 of the 21 patients (76%). Four of 12 patients (33%) with hypertension and two of six patients (33%) with azotemia were improved. End stage renal disease (ESRD) occurred in six of the 21 patients (28%) during the follow-up period. The mean age of ESRD in our patients was 57 years. The mean time interval for the development of ESRD was 19 months. Ablation using a mixture of NBCA and iodized oil may be an effective, safe method for obtaining symptom relief in patients with ADPKD.

  13. Cyst Ablation Using a Mixture of N-Butyl Cyanoacrylate and Iodized Oil in Patients with Autosomal Dominant Polycystic Kidney Disease: the Long-Term Results

    International Nuclear Information System (INIS)

    We wanted to assess the long-term results of cyst ablation with using N-butyl cyanoacrylate (NBCA) and iodized oil in patients with autosomal dominant polycystic kidney disease (ADPKD) and symptomatic cysts. Cyst ablation using a mixture of NBCA and iodized oil was performed in 99 cysts from 21 patients who had such symptoms as abdominal distension and pain. The collapse or reaccumulation of the ablated cysts after the procedure was assessed during the follow-up period of 36 to 90 months. The treatment effects, including symptom relief, and the clinical data such as the blood pressure and serum creatinine levels were also assessed, together with the complications. The procedure was technically successful in all 99 cysts from the 21 patients. Any procedure-related significant complications were not detected. Seventy-seven of 99 cysts (78%) were successfully collapsed on the follow-up CT. Twenty-two cysts showed reaccumulation during long-term follow-up period. The clinical symptoms were relieved in 17 of the 21 patients (76%). Four of 12 patients (33%) with hypertension and two of six patients (33%) with azotemia were improved. End stage renal disease (ESRD) occurred in six of the 21 patients (28%) during the follow-up period. The mean age of ESRD in our patients was 57 years. The mean time interval for the development of ESRD was 19 months. Ablation using a mixture of NBCA and iodized oil may be an effective, safe method for obtaining symptom relief in patients with ADPKD

  14. Identification of Two Disease-causing Genes TJP2 and GJB2 in a Chinese Family with Unconditional Autosomal Dominant Nonsyndromic Hereditary Hearing Impairment

    Directory of Open Access Journals (Sweden)

    Hong-Yang Wang

    2015-01-01

    Full Text Available Background: There are more than 300 genetic loci that have been found to be related to hereditary hearing impairment (HHI, including 92 causative genes for nonsyndromic hearing loss, among which 34 genes are related to autosomal dominant nonsyndromic HHI (ADNSHHI. Traditional linkage analysis and candidate gene sequencing are not effective at detecting the ADNSHHI, especially for the unconditional families that may have more than one pathogenic cause. This study identified two disease-causing genes TJP2 and GJB2 in a Chinese family with unconditional ADNSHHI. Methods: To decipher the genetic code of a Chinese family (family 686 with ADNSHHI, different gene screening techniques have been performed, including linkage analysis, candidate genes screening, high-throughput sequencing and Sanger sequencing. These techniques were done on samples obtained from this family over a period of 10 years. Results: We identified a pathogenic missense mutation, c. 2081G>A (p.G694E, in TJP2, a gene that plays a crucial role in apoptosis and age-related hearing loss (ARHL. The mutation was co-segregated in this pedigree in all, but not in the two patients who presented with different phenotypes from the other affected family members. In one of the two patients, we confirmed that the compound heterozygosity for p.Y136FNx01 and p.G45E in the GJB2 gene may account for the phenotype shown in this patient. Conclusions: We identified the co-occurrence of two genetic causes in family 686. The possible disease-causing missense mutation of TJP2 in family 686 presents an opportunity for further investigation into ARHL. It is necessary to combine various genes screening methods, especially for some unconventional cases.

  15. Limited ATF4 Expression in Degenerating Retinas with Ongoing ER Stress Promotes Photoreceptor Survival in a Mouse Model of Autosomal Dominant Retinitis Pigmentosa

    Science.gov (United States)

    Bhootada, Yogesh; Kotla, Pravallika; Zolotukhin, Sergei; Gorbatyuk, Oleg; Bebok, Zsuzsanna; Athar, Mohammad; Gorbatyuk, Marina

    2016-01-01

    T17M rhodopsin expression in rod photoreceptors leads to severe retinal degeneration and is associated with the activation of ER stress related Unfolded Protein Response (UPR) signaling. Here, we show a novel role of a UPR transcription factor, ATF4, in photoreceptor cellular pathology. We demonstrated a pro-death role for ATF4 overexpression during autosomal dominant retinitis pigmentosa (ADRP). Based on our results in ATF4 knockout mice and adeno-associated viral (AAV) delivery of ATF4 to the retina, we validated a novel therapeutic approach targeting ATF4 over the course of retinal degeneration. In T17M rhodopsin retinas, we observed ATF4 overexpression concomitantly with reduction of p62 and elevation of p53 levels. These molecular alterations, together with increased CHOP and caspase-3/7 activity, possibly contributed to the mechanism of photoreceptor cell loss. Conversely, ATF4 knockdown retarded retinal degeneration in 1-month-old T17M Rhodopsin mice and promoted photoreceptor survival, as measured by scotopic and photopic ERGs and photoreceptor nuclei row counts. Similarly, ATF4 knockdown also markedly delayed retinal degeneration in 3-month-old ADRP animals. This delay was accompanied by a dramatic decrease in UPR signaling, the launching of anti-oxidant defense, initiation of autophagy, and improvement of rhodopsin biosynthesis which together perhaps combat the cellular stress associated with T17M rhodopsin. Our data indicate that augmented ATF4 signals during retinal degeneration plays a cytotoxic role by triggering photoreceptor cell death. Future ADRP therapy regulating ATF4 expression can be developed to treat retinal degenerative disorders associated with activated UPR. PMID:27144303

  16. Analysis of opa1 isoforms expression and apoptosis regulation in autosomal dominant optic atrophy (ADOA) patients with mutations in the opa1 gene.

    Science.gov (United States)

    Formichi, Patrizia; Radi, Elena; Giorgi, Eleonora; Gallus, Gian Nicola; Brunetti, Jlenia; Battisti, Carla; Rufa, Alessandra; Dotti, Maria Teresa; Franceschini, Rossella; Bracci, Luisa; Federico, Antonio

    2015-04-15

    Autosomal dominant optic atrophy (ADOA) is a hereditary optic neuropathy characterized by bilateral symmetrical visual loss, decrease in retinal ganglion cells and a loss of myelin within the optic nerve. ADOA is associated to mutations in Optic atrophy 1 gene (OPA1), which encodes a mitochondrial protein involved in cristae remodeling, maintenance of mitochondrial membrane integrity, mitochondrial fusion and apoptosis regulation. We thus evaluated the rate of apoptosis and the expression levels of OPA1 isoforms in ADOA and control cells. Peripheral blood lymphocytes from eight patients with OPA1 mutation and age matched controls were cultivated both in basal conditions or with 2-deoxy-D-ribose, a reducing sugar that induces apoptosis through oxidative stress. Apoptosis was analyzed by flow cytometry, phosphatidylserine translocation, mitochondrial membrane depolarization and caspase 3 activation. We also analyzed the expression levels of OPA1 isoforms in ADOA and control cells cultured with and without 2-deoxy-D-ribose. We showed an increased percentage of apoptotic cells in ADOA patients compared to controls, both in basal culture conditions and after 2-deoxy-D-ribose treatment. This suggested a great susceptibility of ADOA cells to oxidative stress and a strong correlation between OPA1 protein dysfunctions and morphological-functional alterations to mitochondria. Moreover OPA1 protein expression was significantly decreased in lymphocytes from the ADOA patients after 2-deoxy-D-ribose treatment, implying a great sensitivity of the mutated protein to free radical damage. Concluding, we could confirm that oxidative stress-induced apoptosis may play a key role in the pathophysiological process bringing to retinal ganglion cells degeneration in ADOA. PMID:25796301

  17. Erythropoietin production in renal cell carcinoma and renal cysts in autosomal dominant polycystic kidney disease in a chronic dialysis patient with polycythemia: A case report.

    Science.gov (United States)

    Ito, Keiichi; Asano, Takako; Tominaga, Susumu; Yoshii, Hidehiko; Sawazaki, Harutake; Asano, Tomohiko

    2014-11-01

    In patients undergoing chronic hemodialysis (HD), erythropoietin (EPO) production from the kidney generally decreases and renal anemia develops. Patients without anemia, but with high serum EPO (sEPO) levels are rare among HD patients. The current study presents the case of a 67-year-old female HD patient with autosomal dominant polycystic kidney disease (ADPKD) and renal cell carcinoma (RCC), manifesting polycythemia with elevated sEPO levels. A radical nephrectomy was performed, which diminished the polycythemia, but the sEPO levels remained high. To determine the origin of the EPO production, immunohistochemistry was performed to detect EPO in the RCC and the renal cysts of the surgically resected kidney. In addition, the sEPO and EPO levels in a renal cyst were determined by enzyme immunoassay. EPO expression was demonstrated in RCC and cyst epithelial cells using immunohistochemistry, revealing extremely high EPO levels in the cyst fluid. Due to the remission of polycythemia following the nephrectomy, EPO production from the resected kidney appeared to have been the cause of the polycythemia. Positive EPO staining of the renal cysts in the resected polycystic kidney and sustained sEPO elevation following nephrectomy led to the hypothesis of EPO production in the renal cysts of the contralateral polycystic kidney. Although the postoperative EPO level was higher than the normal range, the hematocrit (Hct) level gradually decreased and recombinant human EPO was required again three months following the nephrectomy. Eight months after the nephrectomy, the Hct level was 30.2% with the use of rHuEPO. In conclusion, EPO production from RCC and renal cysts in ADPKD appeared to cause polycythemia in the HD patient. PMID:25295086

  18. Calcilytic Ameliorates Abnormalities of Mutant Calcium-Sensing Receptor (CaSR) Knock-In Mice Mimicking Autosomal Dominant Hypocalcemia (ADH).

    Science.gov (United States)

    Dong, Bingzi; Endo, Itsuro; Ohnishi, Yukiyo; Kondo, Takeshi; Hasegawa, Tomoka; Amizuka, Norio; Kiyonari, Hiroshi; Shioi, Go; Abe, Masahiro; Fukumoto, Seiji; Matsumoto, Toshio

    2015-11-01

    Activating mutations of calcium-sensing receptor (CaSR) cause autosomal dominant hypocalcemia (ADH). ADH patients develop hypocalcemia, hyperphosphatemia, and hypercalciuria, similar to the clinical features of hypoparathyroidism. The current treatment of ADH is similar to the other forms of hypoparathyroidism, using active vitamin D3 or parathyroid hormone (PTH). However, these treatments aggravate hypercalciuria and renal calcification. Thus, new therapeutic strategies for ADH are needed. Calcilytics are allosteric antagonists of CaSR, and may be effective for the treatment of ADH caused by activating mutations of CaSR. In order to examine the effect of calcilytic JTT-305/MK-5442 on CaSR harboring activating mutations in the extracellular and transmembrane domains in vitro, we first transfected a mutated CaSR gene into HEK cells. JTT-305/MK-5442 suppressed the hypersensitivity to extracellular Ca(2+) of HEK cells transfected with the CaSR gene with activating mutations in the extracellular and transmembrane domains. We then selected two activating mutations locating in the extracellular (C129S) and transmembrane (A843E) domains, and generated two strains of CaSR knock-in mice to build an ADH mouse model. Both mutant mice mimicked almost all the clinical features of human ADH. JTT-305/MK-5442 treatment in vivo increased urinary cAMP excretion, improved serum and urinary calcium and phosphate levels by stimulating endogenous PTH secretion, and prevented renal calcification. In contrast, PTH(1-34) treatment normalized serum calcium and phosphate but could not reduce hypercalciuria or renal calcification. CaSR knock-in mice exhibited low bone turnover due to the deficiency of PTH, and JTT-305/MK-5442 as well as PTH(1-34) increased bone turnover and bone mineral density (BMD) in these mice. These results demonstrate that calcilytics can reverse almost all the phenotypes of ADH including hypercalciuria and renal calcification, and suggest that calcilytics can become a

  19. Waardinburg syndrome — inherited deafness with pigmentary involvement

    Directory of Open Access Journals (Sweden)

    M.F. Macrae

    1979-09-01

    Full Text Available The Waardenburg syndrome was first clearly defined in 1951. The major clinical importance lies in the fact that about 20% of affected individuals are deaf. Furthermore, because the condition is inherited autosomal dominantly, there is a risk of the disorder being handed down from generation to generation. The syndrome consists of six major features which may appear in any combination and to any degree in the affected individual.

  20. Cyst infection in hospital-admitted autosomal dominant polycystic kidney disease patients is predominantly multifocal and associated with kidney and liver volume

    International Nuclear Information System (INIS)

    Positron-emission tomography/computed tomography (PET/CT) has improved cyst infection (CI) management in autosomal dominant polycystic kidney disease (ADPKD). The determinants of kidney and/or liver involvement, however, remain uncertain. In this study, we evaluated clinical and imaging factors associated with CI in kidney (KCI) and liver (LCI) in ADPKD. A retrospective cohort study was performed in hospital-admitted ADPKD patients with suspected CI. Clinical, imaging and surgical data were analyzed. Features of infected cysts were evaluated by PET/CT. Total kidney (TKV) and liver (TLV) volumes were measured by CT-derived multiplanar reconstruction. CI was detected in 18 patients who experienced 24 episodes during an interval of 30 months (LCI in 12, KCI in 10 and concomitant infection in 2). Sensitivities of CT, magnetic resonance imaging and PET/CT were 25.0, 71.4, and 95.0%. Dysuria (P<0.05), positive urine culture (P<0.01), and previous hematuria (P<0.05) were associated with KCI. Weight loss (P<0.01) and increased C-reactive protein levels (P<0.05) were associated with LCI. PET/CT revealed that three or more infected cysts were present in 70% of the episodes. TKV was higher in kidney-affected than in LCI patients (AUC=0.91, P<0.05), with a cut-off of 2502 mL (72.7% sensitivity, 100.0% specificity). TLV was higher in liver-affected than in KCI patients (AUC=0.89, P<0.01) with a cut-off of 2815 mL (80.0% sensitivity, 87.5% specificity). A greater need for invasive procedures was observed in LCI (P<0.01), and the overall mortality was 20.8%. This study supports PET/CT as the most sensitive imaging method for diagnosis of cyst infection, confirms the multifocal nature of most hospital-admitted episodes, and reveals an association of kidney and liver volumes with this complication

  1. Expression and localization of nuclear proteins in autosomal-dominant Emery-Dreifuss muscular dystrophy with LMNA R377H mutation

    Directory of Open Access Journals (Sweden)

    Ewald Andrea

    2004-03-01

    Full Text Available Abstract Background The autosomal dominant form of Emery-Dreifuss muscular dystrophy (AD-EDMD is caused by mutations in the gene encoding for the lamins A and C (LMNA. Lamins are intermediate filament proteins which form the nuclear lamina underlying the inner nuclear membrane. We have studied the expression and the localization of nuclear envelope proteins in three different cell types and muscle tissue of an AD-EDMD patient carrying a point mutation R377H in the lamin A/C gene. Results Lymphoblastoid cells, skin fibroblasts, primary myoblasts and muscle thin sections were studied by immunocytochemistry and electron microscopy. Cellular levels of A-type lamins were reduced compared to control cells. In contrast, the amount of emerin and lamin B appeared unaltered. Cell synchronization experiments showed that the reduction of the cellular level of A-type lamin was due to instability of lamin A. By electron microscopy, we identified a proportion of nuclei with morphological alterations in lymphoblastoid cells, fibroblasts and mature muscle fibres. Immunofluorescence microscopy showed that a major population of the lamin B receptor (LBR, an inner nuclear membrane protein, was recovered in the cytoplasm in association with the ER. In addition, the intranuclear organization of the active form of RNA polymerase II was markedly different in cells of this AD-EDMD patient. This aberrant intranuclear distribution was specifically observed in muscle cells where the pathology of EDMD predominates. Conclusions From our results we conclude: Firstly, that structural alterations of the nuclei which are found only in a minor fraction of lymphoblastoid cells and mature muscle fibres are not sufficient to explain the clinical pathology of EDMD; Secondly, that wild type lamin A is required not only for the retention of LBR in the inner nuclear membrane but also for a correct localization of the transcriptionally active RNA pol II in muscle cells. We speculate that

  2. Familial megacalyces with autosomal recessive inheritance

    International Nuclear Information System (INIS)

    Three children with bilateral congenital megacalyces from a consanguinous marriage are reported. No renal abnormality was detected in the parents. Our observation supports the genetic nature of the disease. The ultrasonographic features of congenital megacalyces are described. (orig.)

  3. Dominant male sterility in sorghum: effect of nuclear background on inheritance of tissue-culture-induced mutation.

    Science.gov (United States)

    Elkonin, Lev A

    2005-11-01

    Occurrence of genetic instability and formation of stable mutations are basic genetic processes. This study demonstrates that nuclear background may influence the formation of stable dominant nuclear gene of male sterility (MS) on the basis of unstable mutation, which was induced in tissue culture of the sorghum haploid (cv. Milo-145). The mutants with complete or partial MS segregated in variable ratios in the progenies of diploid regenerants were obtained from different experiments on cultivation of haploid tissues. In the Milo-145 genetic background the mutation demonstrated somatic instability and was gradually eliminated by self-pollination of partially sterile plants. Hybridization of the MS-plants with the sorghum line SK-723, a fertility-restorer of the cytoplasmic MS A1 (milo) type, maintained the induced mutation. By repeated backcrossing of MS-plants with SK-723, the male-sterile versions of this line (SK-723- Ms(tc)) have been created. In BC-generations, fertile, partially and completely sterile plants were observed. The MS-plants from BC-generations are proposed to contain a dominant gene Ms(tc) while fertile plants were ms(tc)/ms(tc) homozygotes. Crossing the original MS-plants with SK-723 was a key factor in stabilization of the Ms(tc) gene. Dominant expression of the Ms(tc) was observed in male-sterile versions of other sorghum lines created by backcrossing to SK-723- Ms(tc). The lines fertility-restorers for this mutation have been revealed. In the crosses of restored F1 hybrids with emasculated plants of the non-restoring line, the Ms(tc) has been transferred through the pollen and manifested in the F1 generation. The possibility of the Ms(tc) originating as a result of interaction of an unstable allele of the Milo-145 with the SK-723 genome is discussed. PMID:16205908

  4. INF2 mutations associated with dominant inherited intermediate Charcot-Marie-Tooth neuropathy with focal segmental glomerulosclerosis in two Chinese patients.

    Science.gov (United States)

    Jin, Suqin; Wang, Wei; Wang, Renbin; Lv, He; Zhang, Wei; Wang, Zhaoxia; Jiao, Jinsong; Yuan, Yun

    2015-01-01

    Recently, mutations in the inverted formin 2 (INF2) gene have been indentified in patients with dominant inherited intermediate Charcot-Marie-Tooth neuropathy (DI-CMT) with focal segmental glomerulosclerosis (FSGS). We report clinical and nerve pathological changes in two Chinese patients. Case 1 is 27 years old and presented with distal muscle weakness and atrophy of legs at the age of 13 and renal failure at the age of 26. Three of his family members died due to pure renal failure. Case 2 is 22 years old and presented with distal muscle weakness and atrophy of the legs with transient attacks of difficulty in speaking at age 17. Proteinuria was found by routine urine test at the same time. Sural nerve biopsy revealed moderate-to-severe loss of myelinated fibers with union bulbs and regeneration clusters in both patients. Ultrastructurally, numerous elongated extensions of Schwann cells of unmyelinated fibers could be seen in both patients. INF2 gene mutation screening revealed c.451 T>C in case 1 and c.341 G>A in case 2. This is the first report of Chinese patients with INF2-related DI-CMT. The c.451 T>C mutant was responsible for both isolated FSGS and a dual phenotype of FSGS and neuropathy within one family. Intrafamilial variability can be found with the same INF2 mutation. The CNS manifestations further broadened the clinical spectrum of INF2- associated disorders. PMID:25943269

  5. Nuclear gene causing multiple mtDNA deletions in autosomal dominant ophthalmoplegia maps to a distinct chromosomal region - involvement of both nuclear and mitochondrial DNA in a single disorder

    Energy Technology Data Exchange (ETDEWEB)

    Suomalainen, A.; Kaukonen, J.; Timonen, R. [Univ. of Helsinki (Finland)] [and others

    1994-09-01

    Autosomal dominant progressive external ophthalmoplegia (adPEO) is a mitochondrial disease characterized by muscle weakness, most prominent in ocular muscles. The symptoms are caused by accumulation of multiple large deletions of mitochondrial DNA (mtDNA) in the tissues of the patient, especially in those tissues that are most dependent on oxidative metabolism: brain, skeletal muscle and heart. However, the disorder shows autosomal dominant way of transmission, suggesting a primary defect in a nuclear encoded protein, which only secondarily results in mtDNA deletions. The candidate genes could be those actively participating in the mtDNA replication, or those associated with oxidative metabolism and e.g. via overproduction or inefficient elimination of fire oxygen radicals fragmenting mtDNA. We applied random mapping approach to localize the autosomal adPEO gene locus in a large Finnish family. The affected subjects were identified by detection of multiple mtDNA deletions in the Southern blot analysis of DNA extracted from the muscle biopsy specimens. All the family members underwent muscle biopsy. After analysis of 248 highly polymorphic dinucleotide repeat markets dispersed throughout the genome we were able to assign the adPEO gene locus to a distinct chromosomal region with the maximum pairwise lod score of 4.52, recombination fraction 0.0. This is the first evidence that a mutation in a nuclear gene may interfere mtDNA. The pathogenesis of adPEO involves both the genomes: the primary nuclear gene defect leads to secondary mtDNA mutations that cause the symptoms of the patients.

  6. Evaluation of Inheritance Pattern in Mentally Retarded Children

    Directory of Open Access Journals (Sweden)

    F Behnaz

    2011-07-01

    Full Text Available Introduction: Mental retardation is one of the most important problems of general health. The purpose of this study was to evaluate inheritance pattern of mentally retarded patients in Yazd city. Methods: In a descriptive cross- sectional study, all medical records and pedigrees of 320 mentally retarded children whose parents had referred for genetic consultation to the Welfare center of Yazd city were reviewed. Results: Of the total, 62.8% of the parents had consanguineous marriage. Mean inbreeding coefficient of offsprings was 0.0713 in third degree related parents versus 0.0156 in non-related parents. Mental retardation was seen in 43.4% of first– degree relatives of children (6.6% of parents and 36.8% of siblings, respectively. Frequency of mental retardation did not differ significantly in both sexes. Pedigree showed inheritance pattern in 43.4% of patients (autosomal recessive, autosomal dominant and x-linked inheritance pattern were seen in 33.75%, 6.9% and 2.8%, respectively, while 37% of patients had no definite inheritance pattern. Abnormal karyotype were seen in 19.4% of patients, 28 of whom(8.75% of all patients had Down syndrome. The prevalence of autosomal recessive inheritance in patients with consanguineous marriages and non family marriages was 62.8 % and 10%, respectively (P=0. 002. Conclusion: Since multiple cases of mental retardation were seen in families and rate of consanguineous marriage was more in parents of mentally retarded children, genetic counseling in consanguinity marriages and families of mentally retarded children can prevent incidence of mental retardation in these families.

  7. Linkage of autosomal dominant dystrophic epidermolysis bullosa in three British families to the marker D3S2 close to the COL7A1 locus.

    OpenAIRE

    al-Imara, L; Richards, A J; Eady, R A; Leigh, I M; Farrall, M; Pope, F M

    1992-01-01

    Linkage of the anonymous marker D3S2 at 3p21 has been shown in three British families with dominant dystrophic epidermolysis bullosa with a combined lod score of 6.75 at theta = 0. This locus is close to the collagen type VII locus implying that abnormalities of this gene cause dominant dystrophic epidermolysis bullosa.

  8. Autosomal recessive transmission of MYBPC3 mutation results in malignant phenotype of hypertrophic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Yilu Wang

    Full Text Available BACKGROUND: Hypertrophic cardiomyopathy (HCM due to mutations in genes encoding sarcomere proteins is most commonly inherited as an autosomal dominant trait. Since nearly 50% of HCM cases occur in the absence of a family history, a recessive inheritance pattern may be involved. METHODS: A pedigree was identified with suspected autosomal recessive transmission of HCM. Twenty-six HCM-related genes were comprehensively screened for mutations in the proband with targeted second generation sequencing, and the identified mutation was confirmed with bi-directional Sanger sequencing in all family members and 376 healthy controls. RESULTS: A novel missense mutation (c.1469G>T, p.Gly490Val in exon 17 of MYBPC3 was identified. Two siblings with HCM were homozygous for this mutation, whereas other family members were either heterozygous or wild type. Clinical evaluation showed that both homozygotes manifested a typical HCM presentation, but none of others, including 5 adult heterozygous mutation carriers up to 71 years of age, had any clinical evidence of HCM. CONCLUSIONS: Our data identified a MYBPC3 mutation in HCM, which appeared autosomal recessively inherited in this family. The absence of a family history of clinical HCM may be due to not only a de novo mutation, but also recessive mutations that failed to produce a clinical phenotype in heterozygous family members. Therefore, consideration of recessive mutations leading to HCM is essential for risk stratification and genetic counseling.

  9. Dissociation of Pupillary Post-Illumination Responses from Visual Function in Confirmed OPA1 c.983A > G and c.2708_2711delTTAG Autosomal Dominant Optic Atrophy

    DEFF Research Database (Denmark)

    Nissen, Claus; Rönnbäck, Cecilia; Sander, Birgit;

    2015-01-01

    PURPOSE: To test whether the melanopsin-containing, intrinsically photosensitive retinal ganglion cells (ipRGCs), as evaluated by examination of the pupillary light reflex (PLR), are preserved in genetically confirmed autosomal dominant optic atrophy (ADOA). METHOD: Twenty-nine patients with either...... differ significantly from those of healthy controls (blue, p = 0.45, red, p = 0.49, t-test), and no statistically significant effect was noted of peripapillary retinal nerve fiber layer thickness, ganglion cell-inner plexiform layer thickness, or age. CONCLUSION: The PLR to blue light of high luminance...... (300 cd/m(2)) was preserved in both c.983A > G and c.2708_2711delTTAG ADOA despite severe visual loss and optic nerve atrophy. The study confirms, in a large sample of two genetically homogenous groups, that the ipRGCs are spared in ADOA....

  10. Glycine substitutions in the triple-helical region of type VII collagen result in a spectrum of dystrophic epidermolysis bullosa phenotypes and patterns of inheritance

    Energy Technology Data Exchange (ETDEWEB)

    Christiano, A.M.; McGrath, J.A.; Uitto, J. [Thomas Jefferson Univ., Philadelphia, PA (United States); Kong Chong Tan [National Skin Centre (Singapore)

    1996-04-01

    The dystrophic forms of epidermolysis bullosa (DEB) are characterized by fragility of the skin and mucous membranes. DEB can be inherited in either an autosomal dominant or autosomal recessive pattern, and the spectrum of clinical severity is highly variable. The unifying diagnostic hallmark of DEB is abnormalities in the anchoring fibrils, which consist of type VII collagen, and recently, mutations in the corresponding gene, COL7A1, have been disclosed in a number of families. In this study, we report six families with glycine substitution mutations in the triple-helical region of type VII collagen. Among the six families, two demonstrated a mild phenotype, and the inheritance of the mutation was consistent with the dominantly inherited form of DEB. In the four other families, the mutation was silent in the heterozygous state but, when present in the homozygous state, or combined with a second mutation, resulted in a recessively inherited DEB phenotype. Type VII collagen is, therefore, unique among the collagen genes, in that different glycine substitutions can be either silent in heterozygous individuals or result in a dominantly inherited DEB. Inspection of the locations of the glycine substitutions along the COL7A1 polypeptide suggests that the consequences of these mutations, in terms of phenotype and pattern of inheritance, are position independent. 29 refs., 4 figs., 2 tabs.

  11. Autosomal dominant Emery-Dreifuss muscular dystrophy: one case report and literature review%儿童常染色体显性遗传Emery-Dreifuss肌营养不良症1例并文献复习

    Institute of Scientific and Technical Information of China (English)

    伍妘; 张礼萍; 吕俊兰; 郑华; 吴沪生

    2011-01-01

    Objective To study the characteristics and diagnosis of autosomal dominant Emery-Dreifuss muscular dystrophy. Methods The clinical characteristics, diagnosis procedures and histopathological studies of a case with autosomal dominant Emery-Dreifuss muscular dystrophy were analyzed, and genetic analysis was used in the diagnosis of the illness, and the case was reported along with related literature review. Results The patient was a 12 years old girl who showed progressive proximal weakness of all four limbs, rigid spine, remarkable bilateral contractures of Achilles tendons and elbow, as well as slightly increased serum muscle enzymes. Electromyography indicated myogenic change and normal nerve conduction velocities. The pathological changes in muscles showed that the sizes of muscle fibers were different, fiber atrophy and hypertrophy alternately existed, compensatory hypertrophy of partial muscle fibers existed and fat and connective tissue proliferations were apparent. Sequencing of all 12 coding exons of the LMNA gene revealed a c. 746G > A mutation in exon 4, in heterozygous state. It was a missense mutation and resulted in an amino-acid change, p. Arg249Gln. Conclusions Currently, genetic analysis is a reliable method to confirm the diagnosis of autosomal dominant Emery-Dreifuss muscular dystrophy. This article suggests genetic analysis of the LMNA gene in a patient presenting with progressive, bilateral muscle weakness, and early contractures of the elbows. Achilles tendons or rigid spine may be valuable to the early diagnosis of the disease.%目的 提高对常染色体显性遗传Emery-Dreifuss 肌营养不良症(EDMD)的临床和分子生物学特点的认识.方法 总结1例EDMD患儿的临床表现、诊断、肌肉活检病理学和基因检测结果,并综合文献进行分析.结果 女性,12岁,表现为进行性四肢无力,近端为著,脊柱僵硬,伴明显的双侧跟腱、肘挛缩.血浆肌酶轻度升高.肌电图提示肌源性改变,运动

  12. A new autosomal STR nineplex for canine identification and parentage testing

    DEFF Research Database (Denmark)

    van Asch, Barbara; Alves, Cíntia; Gusmão, Leonor;

    2009-01-01

    A single multiplex PCR assay capable of simultaneously amplifying nine canine-specific autosomal STR markers (FH3210, FH3241, FH2004, FH2658, FH4012, REN214L11, FH2010, FH2361 and the newly described C38) was developed for individual identification and parentage testing in domestic dogs. In order...... mixed-breed origin. Co-dominant inheritance of STR alleles was investigated in 101 father, mother and son trios. Expected heterozygosity values vary between 0.5648 for REN214L11 and 0.9050 for C38. The high level of genetic diversity observed for most markers provides this multiplex with a very high...

  13. 常染色体显性遗传视网膜色素变性家系的基因筛查%Screening of candidate genes in a family with autosomal dominant retinitis pigmentosa

    Institute of Scientific and Technical Information of China (English)

    滕云; 田虹; 王慧; 胡晓峰; 陈燕; 杨真荣; 王嵬

    2003-01-01

    目的确定一个常染色体显性遗传视网膜色素变性(autosomal dominant retinitis pigmentosa, ADRP)家系的致病基因及其突变位点和类型.方法应用聚合酶链反应-单链构象多态性结合DNA测序技术,对来自同一家系的4例RP患者及4名正常人外周血DNA进行分子遗传学分析,筛查3个候选基因共8个外显子.结果来自同一家系的4例RP患者均发现有视紫红质基因(rhodopsin, RHO)第1外显子第52密码子存在TTC→TAC的点突变(Phe52Tyr),而4名正常人未发现这种突变.结论在这个中国ADRP大家系中,发现RHO基因的致病突变,表明ADRP存在明显遗传异质性.

  14. The human dorsal spinocerebellar tract: myelinated fiber spectrum and fiber density in controls, autosomal dominant spinocerebellar atrophy, Huntington's chorea, radiation myelopathy, and diseases with peripheral sensory nerve involvement

    Energy Technology Data Exchange (ETDEWEB)

    Ringelstein, E.B.; Schroeder, J.M.

    1982-01-01

    The human dorsal spinocerebellar tract (DSCT) was evaluated morphometrically in 14 control cases of different age and sex using semithin sections of epon-embedded cross sections from the C3, T5, and T10 segments of the spinal cord. A bimodal fiber spectrum was revealed with one peak at 2-3 microns, and a second, broader peak at about 6-8 microns. Fiber density at C3 was 11,188 fibers/mm2 and at T5, 11,156 fibers/mm2. Regression analysis relating fiber density to age disclosed a highly significant loss of myelinated fibers at T5 amounting to about 2.5% per decade. A severe reduction of fiber density and a distinct change in the fiber spectrum with predominant loss of large myelinated fibers were noted in a case of autosomal dominant spinocerebellar atrophy with late onset, and, to a lesser degree, in a case of Huntington's chorea. A subtotal loss of fibers with a persistent normal distribution of fiber sizes was observed rostral to a focus of severe radiation myelopathy, indicating Wallerian degeneration of large numbers of fibers, and a reduction of fiber diameters caudal to the lesion, suggesting retrograde fiber change. By contrast, no primary or transneural changes in the DSCT were detected in six cases of long-term alcoholism, carcinomatous sensory neuropathy, and neurofibromatosis in spite of the involvement of numerous nerve roots.

  15. A novel point mutation in the translation initiation codon of the pre-pro-vasopressin-neurophysin II gene: Cosegregation with morphological abnormalities and clinical symptoms in autosomal dominant neurohypophyseal diabetes insipidus

    Energy Technology Data Exchange (ETDEWEB)

    Rutishauser, J.; Boeni-Schnetzler, M.; Froesch, E.R.; Wichmann, W.; Huisman, T. [Univ. of Zuerich (Switzerland)] [and others

    1996-01-01

    Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a rare variant of idiopathic central diabetes insipidus. Several different mutations in the human vasopressin-neurophysin II (AVP-NP II) gene have been described. We studied nine family members from three generations of an ADNDI pedigree at the clinical, morphological, and molecular levels. AVP concentrations were measured during diagnostic fluid restriction tests. Coronal and sagittal high resolution T1-weighted images of the pituitary were obtained from affected and healthy family members. PCR was used to amplify the AVP-NP II precursor gene, and PCR products were directly sequenced. Under maximal osmotic stimulation, AVP serum levels were close to or below the detection limit in affected individuals. Magnetic resonance imaging studies revealed the characteristic hyperintense ({open_quotes}bright spot{close_quotes}) appearance of the posterior pituitary in two healthy family members. This signal was absent in all four ADNDI patients examined. The coding sequences of AVP and its carrier protein, neurophysin II, were normal in all family members examined. Affected individuals showed a novel single base deletion (G 227) in the translation initiation codon of the AVP-NP II signal peptide on one allele. The mutation in the AVP-NP II leader sequence appears to be responsible for the disease in this kindred, possibly by interfering with protein translocation. The absence of the hyperintense posterior pituitary signal in affected individuals could reflect deficient posterior pituitary function. 56 refs., 4 figs., 3 tabs.

  16. To inherit heritage or to inherit inheritance?

    Directory of Open Access Journals (Sweden)

    Vladimir Krivošejev

    2016-02-01

    Full Text Available The Republic of Serbia is one of the few, if not the only country in the world that, at ratification and translation of the term „baština“– heritage which appears in two significant and related international conventions of UNESCO, used different terms: „baština“– „heritage“, with regard to the Convention Concerning the Protection of the World Cultural and Natural Heritage, and „nasledje“ –inheritance in the Convention for the Safeguarding of the Intangible Cultural Heritage. One of the reasons for the subsequent rejection of the term heritage could lay in the opinion that it was the case of (end of 20th and beginning of the 21st century political bureaucratic introduction of an old, forgotten word, which also contains the notion of gender incorrectness based on pointing out the inheritance through the male line, which could be in conflict with international law. The views expressed in this paper suggest the unsustainability of these claims, as well as greater suitability of the term „baština“– heritage. Namely, the ratification of the Convention Concerning the Protection of the World Cultural and Natural Heritage was done as early as in 1974, and since then the term „baština“– heritage was used, its new introduction into use on the basis of recent daily political aspirations cannot be the case. At the same time inheritance through the male line is encountered with the use of the Latin word „patrimonium“, which is the basis for the terms used in the official translation of the UNESCO-listed conventions in French and Spanish: „patrimoine“ and „patrimonio“ (and other Roman languages so that the use of the term „baština“ –heritage cannot be a violation of international legal norms. Finally, bearing in mind the fact that, in general, use of languages is impossible to achieve complete gender purism, it is necessary to emphasize that in contrast to the term „nasledje“ – inheritance, the

  17. The inheritance of human erythrocyte catechol-O-methyltransferase activity

    International Nuclear Information System (INIS)

    Erythrocyte catechol-O-methyltransferase (COMT) activity was analyzed in 107 individuals from 23 families. The observed activities were consistent with an autosomal codominant inheritance of the gene coding for erythrocyte COMT activity. (author)

  18. 广东地区视网膜色素变性两大家系RHO基因突变分析%Analysis of RHO gene mutation for two autosomal dominant retinitis pigmentosa families in Guangdong Province

    Institute of Scientific and Technical Information of China (English)

    徐志勇; 胡玉华; 陈璐; 黄小菊; 张阮章; 王沙燕

    2009-01-01

    目的 分析广东地区两个常染色体显性遗传视网膜色素变性(autosomal dominant retinRis pigmento-sa,ADRP)家系视紫红质(rhodopsin,RHO)基因突变,探讨基因突变与临床表型的关系.方法 收集广东地区两个常染色体显性遗传视网膜色素变性家系的临床资料,对家系成员进行视力、视野、眼底镜检查;应用聚合酶链反应(PCR)和直接测序技术,对两个家系所有现存成员进行RHO基因检测.结果 发现一家系患者为P347S杂合性突变.另一家系患者存在P171L杂合性突变,两家系的临床表现为发病早,病情进展快,表型较严重,该两家系正常成员均未发现RHO基因突变.结论 RHO基因的P347S与P171L突变分别为该两家系视网膜色素变性的病因.该两种突变均导致较严重的临床表型,与分子基础一致.

  19. Multi-electrode array study of neuronal cultures expressing nicotinic β2-V287L subunits, linked to autosomal dominant nocturnal frontal lobe epilepsy. An in vitro model of spontaneous epilepsy.

    Directory of Open Access Journals (Sweden)

    Francesca eGullo

    2014-07-01

    Full Text Available Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE is a partial sleep-related epilepsy which can be caused by mutant neuronal nicotinic acetylcholine receptors (nAChR. We applied multi-electrode array (MEA recording methods to study the spontaneous firing activity of neocortical cultures obtained from mice expressing or not (WT an ADNFLE-linked nAChR subunit (β2-V287L.More than 100,000 up-states were recorded during experiments sampling from several thousand neurons. Data were analyzed by using a fast sliding-window procedure which computes histograms of the up-state durations. Differently from the WT, cultures expressing β2-V287L displayed long (10-32 s synaptic-induced up-state firing events. The occurrence of such long up-states was prevented by both negative (gabazine, penicillin G and positive (benzodiazepines modulators of GABAA receptors. Carbamazepine (CBZ, a drug of choice in ADNFLE patients, also inhibited the long up-states at micromolar concentrations. In cultures expressing β2-V287L, no significant effect was observed on the action potential waveform either in the absence or in the presence of pharmacological treatment.Our results show that some aspects of the spontaneous hyperexcitability displayed by a murine model of a human channelopathy can be reproduced in neuronal cultures. In particular, our cultures represent an in vitro chronic model of spontaneous epileptiform activity, i.e. not requiring pre-treatment with convulsants. This opens the way to the study in vitro of the role of β2-V287L on synaptic formation. Moreover, our neocortical cultures on MEA platforms allow to determine the effects of prolonged pharmacological treatment on spontaneous network hyperexcitability (which is impossible in the short-living brain slices. Methods such as the one we illustrate in the present paper should also considerably facilitate the preliminary screening of antiepileptic drugs, thereby reducing the number of in vivo

  20. A follow-up study of autosomal dominant polycystic kidney disease with intracranial aneurysms using 3.0 T three-dimensional time-of-flight magnetic resonance angiography

    International Nuclear Information System (INIS)

    Objective: Autosomal dominant polycystic kidney disease (ADPKD) patients have an increased risk for intracranial aneurysms (IAs). Our aim was to screen and follow up the unruptured intracranial aneurysms (UIAs) detected by 3.0 T three-dimensional time-of-flight magnetic resonance angiography (3D-TOF MRA) in patients with ADPKD in order to evaluate the growth of UIAs and the value of 3D-TOF MRA. Methods: From 2011 to 2012, we followed up UIAs detected in 40 ADPKD patients who had MRA examinations with an interval of at least 36 months. All MRA examinations were performed on a 3 T system (Achieva X-Series, Philips Medical Systems) with a Sense-Head-8 receiver head coil. The acquired data sets were transferred to a workstation (EWS, Philips Medical) to perform maximum intensity projection (MIP) and volume rendering (VR) with a specialized software package (Philips Medical). The size of UIAs was determined as the longest diameter in transverse or vertical measurement. UIAs that grew more than 20% were considered as enlarged. Results: Fifty UIAs were found in 40 previously examined ADPKD patients who underwent 3.0 T 3D-TOF MRA follow-ups. No patients ever had treatment before the second examination. The longest diameter of all follow-up UIAs was less than 10 mm and mean diameter was 3.64 ± 2.25 mm. UIAs in only 4 patients (10%) were considered as enlarged. None of the 50 IAs in the 40 ADPKD patients ruptured during the MRA follow-up period. Conclusion: 3.0 T 3D-TOF MRA was feasible for UIAs follow-up in ADPKD patients. The chance of enlargement and rupture of UIAs in ADPKD patients was not higher than in the general population

  1. Congenital insensitivity to pain: Fracturing without apparent skeletal pathobiology caused by an autosomal dominant, second mutation in SCN11A encoding voltage-gated sodium channel 1.9.

    Science.gov (United States)

    Phatarakijnirund, Voraluck; Mumm, Steven; McAlister, William H; Novack, Deborah V; Wenkert, Deborah; Clements, Karen L; Whyte, Michael P

    2016-03-01

    Congenital insensitivity to pain (CIP) comprises the rare heritable disorders without peripheral neuropathy that feature inability to feel pain. Fracturing and joint destruction are common complications, but lack detailed studies of mineral and skeletal homeostasis and bone histology. In 2013, discovery of a heterozygous gain-of-function mutation in SCN11A encoding voltage-gated sodium channel 1.9 (Nav1.9) established a distinctive CIP in three unrelated patients who suffered multiple painless fractures, self-inflicted mutilation, chronic diarrhea, and hyperhidrosis. Here, we studied a mother and two children with CIP by physical examination, biochemical testing, radiological imaging including DXA, iliac crest histology, and mutation analysis. She suffered fractures primarily of her lower extremities beginning at age two years, and had Charcot deformity of both ankles and joint hypermobility. Nerve conduction velocity together with electromyography were normal. Her children had recurrent major fractures beginning in early childhood, joint hypermobility, and chronic diarrhea. She had an excoriated external nare, and both children had hypertrophic scars from scratching. Skin collagen studies were normal. Radiographs revealed fractures and deformities. However, lumbar spine and total hip BMD Z-scores, biochemical parameters of mineral and skeletal homeostasis, and iliac crest histology of the mother (after in vivo tetracycline labeling) were normal. Genomic DNA from the children revealed a unique heterozygous missense mutation in exon 23 (c.3904C>T, p.Leu1302Phe) of SCN11A that is absent in SNP databases and alters an evolutionarily conserved amino acid. This autosomal dominant CIP reflects the second gain-of-function mutation of SCN11A. Perhaps joint hypermobility is an unreported feature. How mutation of Nav1.9 causes fracturing remains unexplained. Lack of injury awareness is typically offered as the reason, and was supported by our unremarkable biochemical

  2. A follow-up study of autosomal dominant polycystic kidney disease with intracranial aneurysms using 3.0 T three-dimensional time-of-flight magnetic resonance angiography

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Tao; Wang, Peng; Qian, Yi [Department of Radiology, Changzheng Hospital, Second Military Medical University, Shanghai (China); Zheng, Xuan [Clinical Nutrition Department of Changhai Hospital, Second Military Medical University, Shanghai (China); Xiao, Liaoyuan [Department of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai (China); Yu, Shengqiang, E-mail: yushengqiang_cz@163.com [Department of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai (China); Liu, Shiyuan, E-mail: laijiangtaotao@163.com [Department of Radiology, Changzheng Hospital, Second Military Medical University, Shanghai (China)

    2013-11-01

    Objective: Autosomal dominant polycystic kidney disease (ADPKD) patients have an increased risk for intracranial aneurysms (IAs). Our aim was to screen and follow up the unruptured intracranial aneurysms (UIAs) detected by 3.0 T three-dimensional time-of-flight magnetic resonance angiography (3D-TOF MRA) in patients with ADPKD in order to evaluate the growth of UIAs and the value of 3D-TOF MRA. Methods: From 2011 to 2012, we followed up UIAs detected in 40 ADPKD patients who had MRA examinations with an interval of at least 36 months. All MRA examinations were performed on a 3 T system (Achieva X-Series, Philips Medical Systems) with a Sense-Head-8 receiver head coil. The acquired data sets were transferred to a workstation (EWS, Philips Medical) to perform maximum intensity projection (MIP) and volume rendering (VR) with a specialized software package (Philips Medical). The size of UIAs was determined as the longest diameter in transverse or vertical measurement. UIAs that grew more than 20% were considered as enlarged. Results: Fifty UIAs were found in 40 previously examined ADPKD patients who underwent 3.0 T 3D-TOF MRA follow-ups. No patients ever had treatment before the second examination. The longest diameter of all follow-up UIAs was less than 10 mm and mean diameter was 3.64 ± 2.25 mm. UIAs in only 4 patients (10%) were considered as enlarged. None of the 50 IAs in the 40 ADPKD patients ruptured during the MRA follow-up period. Conclusion: 3.0 T 3D-TOF MRA was feasible for UIAs follow-up in ADPKD patients. The chance of enlargement and rupture of UIAs in ADPKD patients was not higher than in the general population.

  3. Differences in the evolutionary history of disease genes affected by dominant or recessive mutations

    OpenAIRE

    Albà M Mar; Furney Simon J; López-Bigas Núria

    2006-01-01

    Abstract Background Global analyses of human disease genes by computational methods have yielded important advances in the understanding of human diseases. Generally these studies have treated the group of disease genes uniformly, thus ignoring the type of disease-causing mutations (dominant or recessive). In this report we present a comprehensive study of the evolutionary history of autosomal disease genes separated by mode of inheritance. Results We examine differences in protein and coding...

  4. Inheritance of craniofacial features in Colombian families with class III malocclusion

    Directory of Open Access Journals (Sweden)

    L Otero

    2010-02-01

    Full Text Available L Otero, L Quintero, D Champsaur, E SimancaPontificia Universidad Javeriana, Bogotá, ColombiaIntroduction: The inheritance of class III malocclusion has been well documented, but the inheritance of craniofacial structures in Colombian families with this malocclusion has been not yet reported.Patients and methods: The study sample of 25 families comprised 186 untreated orthodontic individuals from 8 to 60 years old. Pedigrees were drawn using Cyrillic software. Complete family histories for each proband were ascertained and the affection status of relatives was confirmed by lateral cephalograms and facial and dental photographs. Analysis of variance and odds ratio test for each parameter was performed to estimate inheritance from parents to offspring and to determine similar phenotypic features in relatives.Results: The analysis of the pedigrees suggests autosomal dominant inheritance. The craniofacial characteristics that showed more resemblance between parents and offspring were middle facial height, shorter anterior cranial base and mandibular prognathism. In contrast the protrusion of upper lip and maxillary retrusion were the phenotypic features that contributed to class III in the majority of families.Conclusion: Knowledge of the inheritance of craniofacial phenotypes in class III malocclusion will enable the design of new therapies to treat this malocclusion.Keywords: inheritance, craniofacial, phenotype, class III malocclusion

  5. Looking the Cow in the Eye: Deletion in the NID1 Gene Is Associated with Recessive Inherited Cataract in Romagnola Cattle

    OpenAIRE

    Murgiano, Leonardo; Jagannathan, Vidhya; Calderoni, Valerio; Joechler, Monika; Gentile, Arcangelo; Drögemüller, Cord

    2014-01-01

    Cataract is a known condition leading to opacification of the eye lens causing partial or total blindness. Mutations are known to cause autosomal dominant or recessive inherited forms of cataracts in humans, mice, rats, guinea pigs and dogs. The use of large-sized animal models instead of those using mice for the study of this condition has been discussed due to the small size of rodent lenses. Four juvenile-onset cases of bilateral incomplete immature nuclear cataract were recently observed ...

  6. Inheritance Patterns, Dominance and Cross-Resistance of Cry1Ab- and Cry1Ac-Selected Ostrinia furnacalis (Guenée

    Directory of Open Access Journals (Sweden)

    Tiantao Zhang

    2014-09-01

    Full Text Available Two colonies of Asian corn borer, Ostrinia furnacalis (Guenée, artificially selected from a Bt-susceptible colony (ACB-BtS for resistance to Cry1Ab (ACB-AbR and Cry1Ac (ACB-AcR toxins, were used to analyze inheritance patterns of resistance to Cry1 toxins. ACB-AbR and ACB-AcR evolved significant levels of resistance, with resistance ratios (RR of 39-fold and 78.8-fold to Cry1Ab and Cry1Ac, respectively. The susceptibility of ACB-AbR larvae to Cry1Ac and Cry1F toxins, which had not previously been exposed, were significantly reduced, being >113-fold and 48-fold, respectively. Similarly, susceptibility of ACB-AcR larvae to Cry1Ab and Cry1F were also significantly reduced (RR > nine-fold, RR > 18-fold, respectively, indicating cross-resistance among Cry1Ab, Cry1Ac, and Cry1F toxins. However, ACB-AbR and ACB-AcR larvae were equally susceptible to Cry1Ie as were ACB-BtS larvae, indicating no cross-resistance between Cry1Ie and Cry1Ab or Cry1Ac toxins; this may provide considerable benefits in preventing or delaying the evolution of resistance in ACB to Cry1Ab and Cry1Ac toxins. Backcrossing studies indicated that resistance to Cry1Ab toxin was polygenic in ACB-AbR, but monogenic in ACB-AcR, whilst resistance to Cry1Ac toxin was primarily monogenic in both ACB-AbR and ACB-AcR, but polygenic as resistance increased.

  7. Molecular characterization of tissue-nonspecific alkaline phosphatase with an Ala to Thr substitution at position 116 associated with dominantly inherited hypophosphatasia

    OpenAIRE

    2011-01-01

    Abstract Mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene are responsible for hypophosphatasia, an inborn error of bone and teeth metabolism associated with reduced levels of serum alkaline phosphatase activity. A missense mutation (c.346G>A) of TNSALP gene, which converts Ala to Thr at position 116 (according to standardized nomenclature), was reported in dominantly transmitted hypophosphatasia patients (A.S. Lia-Baldini et al. Hum Genet. 109 (2001) 99-108). ...

  8. A novel HSF4 gene mutation (p.R405X causing autosomal recessive congenital cataracts in a large consanguineous family from Pakistan

    Directory of Open Access Journals (Sweden)

    Cheema Abdul

    2008-11-01

    Full Text Available Abstract Background Hereditary cataracts are most frequently inherited as autosomal dominant traits, but can also be inherited in an autosomal recessive or X-linked fashion. To date, 12 loci for autosomal recessive cataracts have been mapped including a locus on chromosome 16q22 containing the disease-causing gene HSF4 (Genbank accession number NM_001040667. Here, we describe a family from Pakistan with the first nonsense mutation in HSF4 thus expanding the mutational spectrum of this heat shock transcription factor gene. Methods A large consanguineous Pakistani family with autosomal recessive cataracts was collected from Quetta. Genetic linkage analysis was performed for the common known autosomal recessive cataracts loci and linkage to a locus containing HSF4 (OMIM 602438 was found. All exons and adjacent splice sites of the heat shock transcription factor 4 gene (HSF4 were sequenced. A mutation-specific restriction enzyme digest (HphI was performed for all family members and unrelated controls. Results The disease phenotype perfectly co-segregated with markers flanking the known cataract gene HSF4, whereas other autosomal recessive loci were excluded. A maximum two-point LOD score with a Zmax = 5.6 at θ = 0 was obtained for D16S421. Direct sequencing of HSF4 revealed the nucleotide exchange c.1213C > T in this family predicting an arginine to stop codon exchange (p.R405X. Conclusion We identified the first nonsense mutation (p.R405X in exon 11 of HSF4 in a large consanguineous Pakistani family with autosomal recessive cataract.

  9. PATTERN OF INHERITANCE OF IDIOPATHIC HYPERCALCIURIA IN TWO FAMILIES

    Directory of Open Access Journals (Sweden)

    A. Nickavar

    2006-09-01

    Full Text Available Idiopathic hypercalciuria is a leading cause of frequency-dysuria syndrome in childhood. Different modes of inheritance have been suggested in this disease. This article presents the occurrence of idiopathic hypercalciuria in all children of two families. In the first family, a 5.5 year old girl with a history of renal stones and dysuria due to hypercalciuria, had two involved brothers and one sister. In the second family, hypercalciuria and medullary nephrocalcinosis were detected in two siblings who were admitted for polyuria and dysuria. Idiopathic type of hypercalciuria was diagnosed in these two families by normal laboratory exams and exclusion of other causes of normocalcemic hypercalciuria. According to the involvement of all offsprings (both sexes in these two families, it is suggested that idiopathic hypercalciuria is an autosomal dominant disease with complete penetration.

  10. Familial heterotaxia: What is the inheritance in this family?

    Energy Technology Data Exchange (ETDEWEB)

    Delatycki, M.B.; Sheffield, L.J. [Royal Children`s Hospital, Victoria (Australia)

    1997-04-14

    Recently, Alonso and colleagues reported on a number of cases of autosomal dominant heterotaxia in the American Journal of Medical Genetics. We would like to report a case of familial heterotaxia whose inheritance is unclear. II-2 and II-3 are sisters married to men who are related neither to themselves nor to each other. III-1 was diagnosed on antenatal ultrasonography as having complex congenital heart disease. Foetal blood sampling was carried out and was normal (46,XX). Postnatally she was found to have a complete atrioventricular septal defect, separate apical VSD, small left ventricle, interrupted inferior vena cava, hypoplastic aortic arch, and aortic coarctation. The child developed necrotising enterocolitis on day 2 and died at age 11 days. Autopsy confirmed these findings; the abdominal organs were all in their normal sites with a single spleen of normal size. 6 refs., 1 fig.

  11. Black hair follicular dysplasia, an autosomal recessive condition in dogs.

    OpenAIRE

    Schmutz, S M; Moker, J S; Clark, E.G.; Shewfelt, R

    1998-01-01

    Using histology, a coat color abnormality and the subsequent hair loss were diagnosed as black hair follicular dysplasia. A pedigree analysis of an affected litter and literature review suggests that this is inherited as an autosomal recessive trait. The melanocyte stimulating hormone receptor gene is ruled out by using linkage analysis.

  12. A Novel Autosomal Recessive GJA1 Missense Mutation Linked to Craniometaphyseal Dysplasia

    Science.gov (United States)

    Hu, Ying; Chen, I-Ping; de Almeida, Salome; Tiziani, Valdenize; Do Amaral, Cassio M. Raposo; Gowrishankar, Kalpana; Passos-Bueno, Maria Rita; Reichenberger, Ernst J.

    2013-01-01

    Craniometaphyseal dysplasia (CMD) is a rare sclerosing skeletal disorder with progressive hyperostosis of craniofacial bones. CMD can be inherited in an autosomal dominant (AD) trait or occur after de novo mutations in the pyrophosphate transporter ANKH. Although the autosomal recessive (AR) form of CMD had been mapped to 6q21-22 the mutation has been elusive. In this study, we performed whole-exome sequencing for one subject with AR CMD and identified a novel missense mutation (c.716G>A, p.Arg239Gln) in the C-terminus of the gap junction protein alpha-1 (GJA1) coding for connexin 43 (Cx43). We confirmed this mutation in 6 individuals from 3 additional families. The homozygous mutation cosegregated only with affected family members. Connexin 43 is a major component of gap junctions in osteoblasts, osteocytes, osteoclasts and chondrocytes. Gap junctions are responsible for the diffusion of low molecular weight molecules between cells. Mutations in Cx43 cause several dominant and recessive disorders involving developmental abnormalities of bone such as dominant and recessive oculodentodigital dysplasia (ODDD; MIM #164200, 257850) and isolated syndactyly type III (MIM #186100), the characteristic digital anomaly in ODDD. However, characteristic ocular and dental features of ODDD as well as syndactyly are absent in patients with the recessive Arg239Gln Cx43 mutation. Bone remodeling mechanisms disrupted by this novel Cx43 mutation remain to be elucidated. PMID:23951358

  13. 常染色体隐性遗传的类Duchenne肌营养不良临床特征及其发生比率的估计值分析%The Proportion and Clinical Feature of Duchenne Muscular Dystrophy With Autosomal Recessive Inheritance

    Institute of Scientific and Technical Information of China (English)

    麻宏伟; 武盈玉; 王阳; 高薇; 薛燕宁

    2001-01-01

    目的:探讨常染色体隐性遗传的类杜氏肌营养不良(类DMD)临床特点及其在杜氏肌营养不良症(DMD)中的比例。方法:研究8个家系中9例女性类DMD的临床表现、家族史及血清肌酸激酶水平,并估计常染色体隐性遗传的类DMD在DMD中的比例。结果:常染色体隐性遗传的类DMD患者独立行走的平均时间为(1.47±1.00)岁,症状出现的平均时间为(8.11±4.32)岁,血清肌酸激酶平均水平为(2785.10±1500.29)U/L,这种常染色体隐性遗传型类DMD占DMD的9.4%。结论:常染色体隐性遗传的类DMD与DMD在临床上无法区别,部分被认为是性连锁隐性遗传的DMD,实际上是常染色体隐性遗传的类DMD。%Objective:Our aim was to investigate the proportion of autosomal recessive (AR) inheritance among families with patients with Duchenne muscular dystrophy (DMD) and clinical feature in patients with AR form of DMD. Methods:A total of 193 families was studied, 8 of them with at least one girl with “DMD - like” phenotype and 185 with only boys with this kind of phenotype. Based on the number of families with at least one affected girl and the number of patients per sibship among these pedigrees, the proportion of families with DMD inherited as an AR trait was estimated. The clinical examination, family history and serum creatine-kinase were studied in 11 patients diagnosed as AR form of DMD. Results: The proportion of families with AR form of DMD was estimated as 9.4%. The average age of being able to walk is (1.47±1.00) year, serum creatine-kinase levels were (2785.10±1500.29) U/L. The clinical symptom occurred at the average age of (8.11±4.32) year in patients with AR form of DMD. Conclusion: The AR form of muscular dystrophy and DMD not be distingushed clinically. Some families with only affected boys diagnosed as typical DMD, in fact, have the AR form of the disease. This study is very useful for genetic consulting.

  14. A Novel Targeted Approach for Noninvasive Detection of Paternally Inherited Mutations in Maternal Plasma.

    Science.gov (United States)

    van den Oever, Jessica M E; van Minderhout, Ivonne J H M; Harteveld, Cornelis L; den Hollander, Nicolette S; Bakker, Egbert; van der Stoep, Nienke; Boon, Elles M J

    2015-09-01

    The challenge in noninvasive prenatal diagnosis for monogenic disorders lies in the detection of low levels of fetal variants in the excess of maternal cell-free plasma DNA. Next-generation sequencing, which is the main method used for noninvasive prenatal testing and diagnosis, can overcome this challenge. However, this method may not be accessible to all genetic laboratories. Moreover, shotgun next-generation sequencing as, for instance, currently applied for noninvasive fetal trisomy screening may not be suitable for the detection of inherited mutations. We have developed a sensitive, mutation-specific, and fast alternative for next-generation sequencing-mediated noninvasive prenatal diagnosis using a PCR-based method. For this proof-of-principle study, noninvasive fetal paternally inherited mutation detection was performed using cell-free DNA from maternal plasma. Preferential amplification of the paternally inherited allele was accomplished through a personalized approach using a blocking probe against maternal sequences in a high-resolution melting curve analysis-based assay. Enhanced detection of the fetal paternally inherited mutation was obtained for both an autosomal dominant and a recessive monogenic disorder by blocking the amplification of maternal sequences in maternal plasma. PMID:26162331

  15. X-chromosome-linked inheritance of the variant thyroxine-binding globulin in Australian aborigines.

    Science.gov (United States)

    Refetoff, S; Murata, Y

    1985-02-01

    The inheritance of quantitative changes in serum T4-binding globulin (TBG; reduced or elevated serum levels) and electrophoretic variants of TBG have been shown to be X-chromosome linked. However, it recently was suggested that another TBG variant, widely distributed in the Australian Aborigine population, may be inherited as an autosomal dominant trait. This communication deals with studies directed to the elucidation of the mode of inheritance of the Aboriginal variant TBG. By measuring the rate of denaturation of TBG at 56 C, we identified three distinct types of TBG in Australian Aborigines. One was a relatively heat-stable TBG (mean t1/2, 58.0 min; range, 68-53 min; group A), indistinguishable from TBG in caucasians (mean t1/2, 55.1; range, 67-43); another was a heat-labile TBG (mean t1/2, 20.8 min; range, 23.7-18.4 min; group C); and a third had intermediate values (mean t1/2, 35.7 min; range, 39.5-30.6 min; group B). Serum samples from the latter group belonged exclusively to women. Assuming that individuals from group A were homozygous for the caucasian type TBG (TBGCC), those from group C were homozygous for the Aboriginal variant of TBG (TBGAA), and individuals from group B were heterozygous (TBGCA), gene frequencies were calculated for the product of TBGC and TBGA, and the incidence of expected genotypes was compared to that observed. The results are compatible with X-chromosome, but not autosomal, inheritance, with a gene frequency of TBGC of 0.4118 and of TBGA of 0.5882. The ability to identify individuals who are heterozygous for the Aboriginal variant TBG confirmed that the structural gene of TBG in man is located on the X-chromosome. PMID:3917459

  16. Inheritance of seed color in Capsicum.

    Science.gov (United States)

    Zewdie, Y; Bosland, P W

    2003-01-01

    The mode of seed color inheritance in Capsicum was studied via an interspecific hybridization between C. pubescens Ruiz and Pav. (black seed color) and C. eximium Hunz. (yellow seed color). Black seed color was dominant over yellow seed color. The F(2) segregation pattern showed continuous variation. The generation means analysis indicated the presence of a significant effect of additive [d], dominance [h], and additive x additive [i] interaction for seed color inheritance. The estimate for a minimum number of effective factors (genes) involved in seed color inheritance was approximately 3. PMID:12920108

  17. 一个视网膜色素变性家系的视紫红质基因突变分析%A recurrent rhodopsin gene missense mutation in a Chinese family with autosomal dominant retinitis pigmentosa

    Institute of Scientific and Technical Information of China (English)

    王沙燕; 张阮章; 石之驎; 任莉莉; 任景慧

    2005-01-01

    目的确定常染色体显性遗传视网膜色素变性家系的致病基因及其突变位点,并研究其临床表型.方法对一个常染色体显性遗传视网膜色素变性(autosomal dominat retinitis pigmentosa,ADRP)家系成员进行了视力、视野及眼底镜检查,并对该家系中先证者进行了视网膜电流图分析.应用聚合酶链反应和直接测序技术,对该家系的所有现存人员的视紫红质基因的外显子进行测序分析.结果该家系的25名成员中12例患者有视紫红质基因(rhodopsin, RHO)的512C>T(P171L)突变,均呈杂合子,该错义突变使密码子171由CCA变成CTA.而未受累者的视紫红质基因表现为野生型.该家系患者的临床表现为5~6岁时出现夜盲,在20~30岁逐渐出现视力和视野损害,并先后在40~50岁前后失明,其中2例患者并发青光眼,先证者的闪烁视网膜电图呈熄灭型.结论视紫红质基因RHO的一种已知突变512C>T(P171L)是该家系的病因.与国外相同的基因突变类型相比较,该家系发病早、病情进展快、视功能损害较重.

  18. A retrospective study of the inheritance of peromelia in Angora goats

    DEFF Research Database (Denmark)

    Agerholm, J.S.; Kielsgaard, M.E.; Pedersen, Jan W.; Kobberoe, S.

    1997-01-01

    Peromelia, agenesia of the distal parts of the limbs, has been reported as a congenital defect in several animal species. In Angora goats, cases occur in a familiar pattern consistent with an autosomal recessively inherited defect. To obtain further evidence on the inheritance of peromelia in Ang...

  19. Herencia de la retinosis pigmentaria en la provincia Camagüey Inheritance of retinitis pigmentosa in the province of Camagüey

    Directory of Open Access Journals (Sweden)

    Elisa Dyce Gordon

    1999-06-01

    Full Text Available Con el objetivo de clasificar a los pacientes con Retinosis Pigmentaria y a sus respectivas familias según la herencia y exponer el valor de dicha clasificación, se realizó un estudio descriptivo con 354 individuos afectados, distribuidos en 191 familias camagüeyanas. A través de entrevistas y la confección e interpretación del árbol genealógico se obtuvieron los datos necesarios. Se realizó estadística descriptiva con pruebas de chi-cuadrado y de probabilidad estadística. El 36,65 % de las familias estuvieron representadas por los casos con herencia no definida (simple seguidas por las herencias autosómica recesiva (27,75 % y autosómica dominante (24,60 %, esta última con el 87 % de penetrancia. Estadísticamente significativa fue la asociación de la consanguinidad con las herencias recesivas ( p A descriptive study of 354 affected individuals distributed in 190 families from Camagüey was conducted aimed at classifying those patients with retinitis pigmentosa and their families according to inheritance and at showing the value of such classification. The necessary data were obtained by interviews and genealogical analysis. A descriptive statistics was presented based on chi square test and statistical probability test. 36,65 % of the families were represent by the cases with indefinite (simple inheritance followed by recessive autosomal inheritances (27,75 % and dominant autosomal inheritance (24,60 %. The latter with 87 % of penetrance. The association of consanguinity with the recesive inheritances was statistically significant (p < ,005. 231 new diagnosis (39,75 % were made among the 581 patients who were examined. Knowing the ways of inheritance of retinis pigmentosa of each patient and this family is very important for screening the affected individuals and for preventing the disease

  20. Digenic inheritance of an SMCHD1 mutation and an FSHD-permissive D4Z4 allele causes facioscapulohumeral muscular dystrophy type 2

    OpenAIRE

    Lemmers, Richard J. L. F.; Tawil, Rabi; Petek, Lisa M.; Balog, Judit; Block, Gregory J.; Santen, Gijs W. E.; Amell, Amanda M.; van der Vliet, Patrick J.; ALmomani, Rowida; Straasheijm, Kirsten R; Krom, Yvonne D.; Klooster, Rinse; Sun, Yu; den Dunnen, Johan T.; Helmer, Quinta

    2012-01-01

    Facioscapulohumeral dystrophy (FSHD) is characterized by chromatin relaxation of the D4Z4 macrosatellite array on chromosome 4 and expression of the D4Z4-encoded DUX4 gene in skeletal muscle. The more common form, autosomal dominant FSHD1, is caused by a contraction of the D4Z4 array, whereas the genetic determinants and inheritance of D4Z4 array contraction-independent FSHD2 are unclear. Here we show that mutations in SMCHD1 (structural maintenance of chromosomes flexible hinge domain contai...

  1. Inherited mitochondrial neuropathies.

    Science.gov (United States)

    Finsterer, Josef

    2011-05-15

    Mitochondrial disorders (MIDs) occasionally manifest as polyneuropathy either as the dominant feature or as one of many other manifestations (inherited mitochondrial neuropathy). MIDs in which polyneuropathy is the dominant feature, include NARP syndrome due to the transition m.8993T>, CMT2A due to MFN2 mutations, CMT2K and CMT4A due to GDAP1 mutations, and axonal/demyelinating neuropathy with external ophthalmoplegia due to POLG1 mutations. MIDs in which polyneuropathy is an inconstant feature among others is the MELAS syndrome, MERRF syndrome, LHON, Mendelian PEO, KSS, Leigh syndrome, MNGIE, SANDO; MIRAS, MEMSA, AHS, MDS (hepato-cerebral form), IOSCA, and ADOA syndrome. In the majority of the cases polyneuropathy presents in a multiplex neuropathy distribution. Nerve conduction studies may reveal either axonal or demyelinated or mixed types of neuropathies. If a hereditary neuropathy is due to mitochondrial dysfunction, the management of these patients is at variance from non-mitochondrial hereditary neuropathies. Patients with mitochondrial hereditary neuropathy need to be carefully investigated for clinical or subclinical involvement of other organs or systems. Supportive treatment with co-factors, antioxidants, alternative energy sources, or lactate lowering agents can be tried. Involvement of other organs may require specific treatment. Mitochondrial neuropathies should be included in the differential diagnosis of hereditary neuropathies. PMID:21402391

  2. Inheritance of Resistance to Deltamethrin in Aedes aegypti (Diptera: Culicidae) From Cuba.

    Science.gov (United States)

    Rodríguez, María Magdalena; Hurtado, Daymi; Severson, David W; Bisset, Juan A

    2014-11-01

    The development of pyrethroid resistance in Aedes aegypti (L) (Diptera: Culicidae) is a serious concern because major A. aegypti control programs are predominantly based on pyrethroid use during epidemic disease outbreaks. Research about the genetic basis for pyrethroid resistance and how it is transmitted among mosquito populations is needed. The objective of this study was to determine how deltamethrin resistance is inherited in the Cuban A. aegypti-resistant reference strain. Here, a field population of A. aegypti from Santiago de Cuba (SAN-F14), subjected to 14 generations of selection for high deltamethrin resistance level (91.25×), was used to prepare reciprocal F1 and backcross progeny with the insecticide-susceptible Rockefeller strain. Bioassays with larvae were performed according to World Health Organization guidelines. The activities of metabolic enzymes were assayed through synergist and biochemical tests. The null hypothesis of the parallelism test between the two probit regression lines of the reciprocal F1 (susceptible females × resistant males and vice versa) was not rejected at the 5% significance level (P = 0.42), indicating autosomal inheritance. The LC50 response of both F1 progenies to deltamethrin was elevated but less than the highly resistant SAN-F14 strain. DLC values for the F1 progenies were 0.91 and 0.87, respectively, suggesting that deltamethrin resistance in the SAN-F14 strain is inherited as an autosomal incompletely dominant trait, involving at least two factors, which implies a faster development of deltamethrin resistance in larvae and lost product effectiveness. Metabolic enzymes including esterases and cytochrome P-450 monooxygenases but not glutathione-S-transferases were involved in deltamethrin resistance in larvae. PMID:26309309

  3. Ventricular arrhythmias in Rhodesian Ridgebacks with a family history of sudden death and results of a pedigree analysis for potential inheritance patterns.

    Science.gov (United States)

    Meurs, Kathryn M; Weidman, Jess A; Rosenthal, Steven L; Lahmers, Kevin K; Friedenberg, Steven G

    2016-05-15

    OBJECTIVE To evaluate a group of related Rhodesian Ridgebacks with a family history of sudden death for the presence of arrhythmia and to identify possible patterns of disease inheritance among these dogs. DESIGN Prospective case series and pedigree investigation. ANIMALS 25 Rhodesian Ridgebacks with shared bloodlines. PROCEDURES Pedigrees of 4 young dogs (1 female and 3 males; age, 7 to 12 months) that died suddenly were evaluated, and owners of closely related dogs were asked to participate in the study. Dogs were evaluated by 24-hour Holter monitoring, standard ECG, echocardiography, or some combination of these to assess cardiac status. Necropsy reports, if available, were reviewed. RESULTS 31 close relatives of the 4 deceased dogs were identified. Of 21 dogs available for examination, 8 (2 males and 6 females) had ventricular tachyarrhythmias (90 to 8,700 ventricular premature complexes [VPCs]/24 h). No dogs had clinical signs of cardiac disease reported. Echocardiographic or necropsy evaluation for 7 of 12 dogs deemed affected (ie, with frequent or complex VPCs or sudden death) did not identify structural lesions. Five of 6 screened parents of affected dogs had 0 to 5 VPCs/24 h (all singlets), consistent with a normal reading. Pedigree evaluation suggested an autosomal recessive pattern of inheritance, but autosomal dominant inheritance with incomplete penetrance could not be ruled out. CONCLUSIONS AND CLINICAL RELEVANCE Holter monitoring of Rhodesian Ridgebacks with a family history of an arrhythmia or sudden death is recommended for early diagnosis of disease. An autosomal recessive pattern of inheritance in the studied dogs was likely, and inbreeding should be strongly discouraged. PMID:27135669

  4. Inheritance patterns and phenotypic features of myofibrillar myopathy associated with a BAG3 mutation

    Science.gov (United States)

    Odgerel, Zagaa; Sarkozy, Anna; Lee, Hee-Suk; McKenna, Caoimhe; Rankin, Julia; Straub, Volker; Lochmüller, Hanns; Paola, Francalanci; D’Amico, Adele; Bertini, Enrico; Bushby, Kate; Goldfarb, Lev G

    2010-01-01

    Myofibrillar myopathies (MFMs) are a heterogeneous group of neuromuscular disorders characterized by disintegration of myofibrils. The inheritance pattern in MFMs is commonly autosomal dominant, but there has been a striking absence of secondary cases noted in a BAG3-associated subtype. We studied three families with BAG3 p.Pro209Leu mutation showing a severe phenotype of myofibrillar myopathy and axonal neuropathy with giant axons. In one family, transmission to a pair of siblings has occurred from their asymptomatic father who showed somatic mosaicism. In two other families, neither of the parents was affected or showed detectable level of somatic mosaicism. These observations suggest that the BAG3 variant of MFM may result from a spontaneous mutation at an early point of embryonic development and that transmission from a mosaic parent may occur more than once. The study underlines the importance of parental evaluation as it may have implications for genetic counseling. PMID:20605452

  5. The scurs inheritance: new insights from the French Charolais breed

    Directory of Open Access Journals (Sweden)

    Gautier Mathieu

    2009-07-01

    Full Text Available Abstract Background Polled animals are valued in cattle industry because the absence of horns has a significant economic impact. However, some cattle are neither polled nor horned but have so-called scurs on their heads, which are corneous growths loosely attached to the skull. A better understanding of the genetic determinism of the scurs phenotype would help to fine map the polled locus. To date, only one study has attempted to map the scurs locus in cattle. Here, we have investigated the inheritance of the scurs phenotype in the French Charolais breed and examined whether the previously proposed localisation of the scurs locus on bovine chromosome 19 could be confirmed or not. Results Our results indicate that the inheritance pattern of the scurs phenotype in the French Charolais breed is autosomal recessive with complete penetrance in both sexes, which is different from what is reported for other breeds. The frequency of the scurs allele (Sc reaches 69.9% in the French Charolais population. Eleven microsatellite markers on bovine chromosome 19 were genotyped in 267 offspring (33 half-sib and full-sib families. Both non-parametric and parametric linkage analyses suggest that in the French Charolais population the scurs locus may not map to the previously identified region. A new analysis of an Angus-Hereford and Hereford-Hereford pedigree published in 1978 enabled us to calculate the frequency of the Sc allele in the Hereford breed (89.4% and to study the penetrance of this allele in males heterozygous for both polled and scurs loci (40%. This led us to revise the inheritance pattern of the scurs phenotype proposed for the Hereford breed and to suggest that allele Sc is not fully but partially dominant in double heterozygous males while it is always recessive in females. Crossbreeding involving the Charolais breed and other breeds gave results similar to those reported in the Hereford breed. Conclusion Our results suggest the existence of

  6. Inheritance versus parameterization

    DEFF Research Database (Denmark)

    Ernst, Erik

    This position paper argues that inheritance and parameterization differ in their fundamental structure, even though they may emulate each other in many ways. Based on this, we claim that certain mechanisms, e.g., final classes, are in conflict with the nature of inheritance, and hence causes...

  7. An autosomal recessive syndrome of cleft palate, cardiac defect, genital anomalies, and ectrodactyly (CCGE).

    OpenAIRE

    Giannotti, A; Digilio, M C; Mingarelli, R; Dallapiccola, B.

    1995-01-01

    We report a brother and sister affected by a constellation of malformations, including cleft palate, cardiac defect, genital anomalies, and ectrodactyly (CCGE). A similar association has been reported previously by Richieri-Costa and Orquizas in a male patient born to consanguineous parents. An autosomal recessive pattern of inheritance is proposed for this syndrome.

  8. Autosomal recessive cerebellar ataxia with bull's-eye macular dystrophy.

    NARCIS (Netherlands)

    Cruysberg, J.R.M.; Eerola, K.U.; Vrijland, H.R.; Aandekerk, A.L.; Kremer, H.P.H.; Deutman, A.F.

    2002-01-01

    PURPOSE: In 1980, we published in the American Journal of Ophthalmology two siblings with hereditary ataxia and atrophic maculopathy. The report is cited in the literature as autosomal dominant cerebellar ataxia with retinal degeneration. The purpose of the present study is to document the progressi

  9. Caroli′s syndrome with autosomal recessive polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    Prithi Shenoy

    2014-01-01

    Full Text Available Caroli′s syndrome (CS is a rare congenital disorder characterized by multiple segmental cystic or saccular dilatations of the intrahepatic bile ducts and congenital hepatic fibrosis. We report a 9-year-old boy who was diagnosed with CS and autosomal recessive poly-cystic kidney disease. On screening, his 5-month-old asymptomatic sister had multiple dilated biliary radicals with multiple bilateral renal cystic lesions. Both the patient and the affected sibling have been advised regular follow-up for monitoring the progression of the disease. In conclusion, patients with CS should be screened for renal cystic lesions and vice versa even if they are asymptomatic. Also, as the disease is inherited in an autosomal recessive manner, it is important to screen family members for early diagnosis and management.

  10. Caroli's syndrome with autosomal recessive polycystic kidney disease.

    Science.gov (United States)

    Shenoy, Prithi; Zaki, Syed Ahmed; Shanbag, Preeti; Bhongade, Swapnil

    2014-07-01

    Caroli's syndrome (CS) is a rare congenital disorder characterized by multiple segmental cystic or saccular dilatations of the intrahepatic bile ducts and congenital hepatic fibrosis. We report a 9-year-old boy who was diagnosed with CS and autosomal recessive poly-cystic kidney disease. On screening, his 5-month-old asymptomatic sister had multiple dilated biliary radicals with multiple bilateral renal cystic lesions. Both the patient and the affected sibling have been advised regular follow-up for monitoring the progression of the disease. In conclusion, patients with CS should be screened for renal cystic lesions and vice versa even if they are asymptomatic. Also, as the disease is inherited in an autosomal recessive manner, it is important to screen family members for early diagnosis and management. PMID:24969198

  11. Analysis of the mutations of rhodopsin gene in autosomal dominant retinitis pigmentosa family%常染色体显性视网膜色素变性家系视紫红质基因突变的检测分析

    Institute of Scientific and Technical Information of China (English)

    马晓晔; 魏锐利; 蔡季平; 朱莉

    2002-01-01

    目的观察一个常染色体显性视网膜色素变性(autosomal dominant retinitis pigmentosa,ADRP)家系的视紫红质(rhodopsin,RHO)基因突变特征. 方法抽取20个ADRP家系成员外周血3~5 ml并提取DNA;聚合酶链反应(polymerase chain reaction,PCR)扩增RHO基因第1~5外显子基因片段, 用直接测序法对20个DNA样本进行RHO基因突变检测. 结果该家系中10例ADRP患者的RHO基因的第182密码子发生G→A置换突变(Gly-182-Asp),而在2例患者和8个未患病家系成员中均未发现此突变. 结论 Gly-182-Asp突变不一定是ADRP家系的致病原因;在RHO基因附近可能存在新的基因, 但还需要进一步研究证明.

  12. Analysis of the mutations of rhodopsin gene in autosomal dominant retinitis pigmentosa family%常染色体显性遗传视网膜色素变性家系视紫红质基因突变分析

    Institute of Scientific and Technical Information of China (English)

    容维宁; 盛迅伦; 庄文娟

    2006-01-01

    目的:观察常染色体显性遗传视网膜色素变性(autosomal dominant RP,ADRP)家系视紫红质基因(rhodopsin,RHO)的突变特征.方法:抽取11个ADRP家系成员的外周血3~5mL,提取DNA;应用聚合酶链反应(polymerase chain reaction,PCR)扩增RHO基因的第1至5外显子基因片断,对PCR产物进行直接测序.结果:在1个家系中有3例ADRP患者297密码子存在杂合的2种类型的密码子(AGC和AGT).另外,该家系在第3外显子3′端下游第4个碱基处发生C-T转换,呈T纯合子的1例,8例呈杂合子状态.结论:Ser-297-Ser系基因多态现象.另外,RHO基因第3外显子3′端下游内含子处发生的C/T多态性是否与RP的发生存在相关性,需进一步研究.

  13. Pain determinants of pain in autosomal dominant polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    José Luiz Nishiura

    2013-09-01

    Full Text Available Pain is the most common symptom reported by ADPKD patients, afflicting approximately 60% of cases and may result from renal hemorrhage, calculi, urinary tract infections, cyst rupture, or due to stretching of the capsule or traction of the renal pedicle. We have recently investigated pain patterns in AD-PKD patients using a translated version of a pain questionnaire specific for AD-PKD population. The questionnaire revealed that 67% patients with ADPKD exhibited some type of pain. The findings of that study emphasized that pain appeared early in the course of ADPKD, when patients still exhibited preserved renal function. In the present study, a multivariate logistic regression analysis disclosed that renal volume (9-fold increased risk and nephrolithiasis (4-fold increased risk were the most important determinant factors for pain in ADPKD patients with preserved renal function, after adjustments for the presence of hypertension and duration of the disease.

  14. Genetics Home Reference: autosomal dominant hyper-IgE syndrome

    Science.gov (United States)

    ... movement ( hyperextensibility ), an abnormal curvature of the spine ( scoliosis ), reduced bone density (osteopenia), and a tendency for ... health conditions: Diagnostic Tests Drug Therapy Surgery and Rehabilitation Genetic Counseling Palliative Care Related Information How are ...

  15. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infacts and Leukoencephalopathy (CADASIL)

    Science.gov (United States)

    ... that tested Donepezil (Aricept), a drug recommended for Alzheimer’s disease, did not find it to be effective in CADASIL. However, some patients may benefit in terms of improved concentration and attention. Other forms of supportive therapies such as physicial therapy and speech therapy are ...

  16. Safe Dynamic Multiple Inheritance

    DEFF Research Database (Denmark)

    Ernst, Erik

    2002-01-01

    Multiple inheritance and similar mechanisms are usually only supported at compile time in statically typed languages. Nevertheless, dynamic multiple inheritance would be very useful in the development of complex systems, because it allows the creation of many related classes without an explosion in...... the size and level of redundancy in the source code. In fact, dynamic multiple inheritance is already available. The language gbeta is statically typed and has supported run-time combination of classes and methods since 1997, by means of the combination operator '&'. However, with certain combinations...

  17. Laryngo-onycho-cutaneous syndrome: an inherited epithelial defect.

    OpenAIRE

    Phillips, R J; Atherton, D J; Gibbs, M L; S. Strobel; Lake, B D

    1994-01-01

    Three children with an unusual but clearly defined combination of clinical findings that appear to have been inherited in an autosomal recessive manner are described. All had developed laryngeal abnormalities, chronic skin ulceration, nail dystrophy, and conjunctival disease in infancy. In every case, dental enamel was hypoplastic and both skin and mucosal surfaces demonstrated increased susceptibility to trauma. Progression of disease occurred, to life threatening respiratory obstruction in ...

  18. A new autosomal recessive disorder of bilateral frontotemporal pachygyria without microcephaly: Report of a case and review of literature

    OpenAIRE

    Phadke Shubha; Girisha K; Phadke Rajendra

    2007-01-01

    Pachygyria is a disorder of neuronal migration. We report an Indian family with four siblings with developmental delay, infrequent seizures, normal head size and mild to moderate mental retardation. Two of them had bilaterally symmetrical frontotemporal pachygyria. Dysmorphism and neurological signs were absent in the affected subjects. Affected male and female siblings with normal parents suggests autosomal recessive mode of inheritance. We believe these cases represent a new autosomal reces...

  19. Mutations of rhodopsin gene in a family with autosomal dominant retinitis pigmentosa%一个常染色体显性视网膜色素变性家系表型分析和RHO基因突变检测

    Institute of Scientific and Technical Information of China (English)

    章雪敏; 刘铁城; 金鑫; 袁慧军; 张宝全; 王瑛

    2012-01-01

    目的 分析一常染色体显性视网膜色素变性(autosomal dominant retinitis pigmentosa,adRP)家系的临床表型,确定该家系与视紫红质(rhodopsin,RHO)基因的关系.方法 依据RP诊断标准及患者临床表型,确定一连续4代发病的adRP家系遗传的特点;采集家系中13位成员外周血8-10ml,提取基因组DNA;聚合酶链反应(polymerase chain reaction,PCR)扩增RHO基因的第1-5外显子基因片段,产物纯化后直接测序;测序结果与美国国立生物技术信息中心(National Center for Biotechnology Information,NCBI)数据库上公布的核酸标准序列进行比对分析.结果 该家系临床特点为所有患者均于10岁左右出现夜盲,1例22岁出现视野损害,2例40岁左右出现视野损害,并且于50岁左右双眼相继发生急性闭角型青光眼和并发性白内障.该家系5例患者在RHO基因外显子、上下游非编码序列以及内含子及外显子拼接部中均未发现碱基改变.结论 本研究家系患者存在遗传异质性和表型异质性,RHO基因不是该家系的致病基因.%Objective To study the relation between a family with autosomal dominant retinitis pigmentosa(adRP) and rhodopsin (RHO) by analyzing the clinical phenotype of adRP. Methods Genetic characteristics of the family with adRP occurring in 4 consecutive generations were observed according to the RP diagnostic criteria of retinitis pigmentosa(RP) and the clinical phenotype of the adRP family members. Peripheral blood samples(8-10ml) were taken from 13 family members of the family with adRP. Genomic DNA was isolated and the first 5 exons of RHO gene segments were amplified by PCR. The purified PCR products were directly sequenced, which was compared with the standard sequence of nucleic acid from National Center for Biotechnology Information(NCBl). Results Night blindness occurred in all members of the family at the age of about 10 years. Visual field damage was observed in 1 member at the age of

  20. Detection of PKD1 mutations in autosomal dominant polycystic kidney disease by Ion Torrent semiconductor sequencing%应用Ion Torrent半导体测序技术检测常染色体显性多囊肾患者PKD1基因致病突变

    Institute of Scientific and Technical Information of China (English)

    马定远; 胡平; 罗春玉; 张菁菁; 成建; 王玉国; 蒋涛; 许争峰

    2015-01-01

    目的 基于Ion Torrent半导体测序技术建立常染色体显性多囊肾患者PKD1基因致病突变检测方法并评价其临床应用价值.方法 遗传病分子诊断.收集2013年7月至2014年8月在南京市妇幼保健院就诊的多囊肾患者5例,提取外周血DNA,采用9个长链PCR反应特异性扩增PKD1基因全部编码区,PCR产物混合后进行酶切,经模板制备、乳液PCR和磁珠颗粒富集,应用Ion Torrent个体化基因组测序仪进行PKD1基因测序,对发现的致病突变通过Sanger测序验证.结果 应用Ion Torrent半导体测序技术检测到4例患者存在PKD1基因致病突变,分别为外显子12微小缺失突变(c.2966_2970delCGGCG),外显子15微小缺失突变(c.5014_5015delAG),内含子23剪接位点突变(c.8972-2A> G),外显子36错义突变(c.10675G> A).结论 基于长链PCR技术和Ion Torrent 半导体测序技术,建立了常染色体显性多囊肾病基因诊断方法,该方法能够特异性检测PKD1基因致病突变,具有较高的临床应用价值.%Objective To develop and validate a method for detectiug PKD1 mutations in autosomal dominant polycystic kidney disease by Ion Torrent semiconductor sequencing.Methods Molecular diagnosis of genetic diseases.Five Chinese patients with polycystic kidney disease were recruited frown Nanjing Maternity and Child Health Care Hospital for genetic counseling from July 2013 to August 2014.Peripheral blood samples were collected for DNA analysis.The entire PKD1 coding region was amplified by nine long-range PCR reactions.Pooled amplicons from individual patients were sheared to short fragments using fragmentase.After template preparation,emulsion PCR,and ion sphere particles enrichment,the barcoded libraries were subsequently sequenced using the Ion Torrent sequencer.Candidate variants were validated by Sanger sequencing.Results By using the targeted Ion Torrent sequencing method,four PKD1 mutations were identified from 4 patients,including c.2966

  1. Aneurisma gigante do segmento intracavernoso da carótida interna associado a doença renal policística autossômica dominante: relato de caso Giant aneurysm of the intracavernous internal carotid artery associated with autosomal dominant polycystic kidney disease: case report

    Directory of Open Access Journals (Sweden)

    Keven F. Ponte

    2006-09-01

    Full Text Available Apresenta-se o caso de mulher de 60 anos com doença renal policística autossômica dominante (DRPAD que desenvolveu quadro de cefaléia e oftalmoplegia completa à direita. A TC levantou a hipótese de um aneurisma gigante do segmento intracavernoso da carótida interna direita, o que foi confirmado pela arteriografia. Realizou-se, então, tratamento endovascular por oclusão do vaso parental com molas destacáveis no segmento supraclinóideo. A paciente evoluiu com a interrupção da cefaléia e com redução parcial da ptose e da oftalmoplegia. Neste artigo, enfatiza-se a relação entre DRPAD e aneurismas intracranianos. Comenta-se a história natural dos aneurismas originados no segmento intracavernoso da artéria carótida interna e comparam-se as opções terapêuticas no manejo destas lesões.We report the case of a 60 years-old woman with autosomal dominant polycystic kidney disease (ADPKD that presented with headache and right complete ophthalmoplegia. The CT scan raised the possibility of a giant aneurysm of the right intracavernous internal carotid artery, confirmed by angiography. The patient underwent endovascular occlusion of parent vessel with detachable coils, then she presented interruption of headache and partial recovery of ptosis and ophthalmoplegia. We emphasize the relationship between ADPKD and intracranial aneurysms. We also discuss the natural history and compare the therapeutic options for the management of giant aneurysms of the cavernous portion of the carotid artery.

  2. Real Estate Inheritance in Austria

    OpenAIRE

    Pirmin Fessler; Peter Mooslechner; Martin Schürz

    2010-01-01

    As real estate inheritances are an important component of Austrian households’ assets, they are relevant for monetary policymaking and for the maintenance of financial stability. 20% of Austrian households have inherited real estate wealth, with some 2% of all households accounting for around 40% of the overall volume of real estate inheritances in Austria. In aggregate, real estate inheritances constitute up to 23% of households’ total real estate wealth. Households which have inherited diff...

  3. Inheritance is Specialisation

    DEFF Research Database (Denmark)

    Torgersen, Mads

    How can we get a simpler but much more general subclass construct? This position paper takes a "specialisationist" approach to inheritance. Old SIMULA virtues are restored to prominence, but boiled with new unificational ingredients to obtain a substrate of specialisation. Ever since the advent of...... Smalltalk there has been a strong tension in the object-oriented community between two opposing views of the role of inheritance: as an incremental modification mechanism or as a vehicle for conceptual modelling. Madsen [5] and many others characterise the two approaches as the “American ” and “Scandinavian......” schools, respectively. Nowadays, such a geographical terminology hardly remains valid (if ever it was), but the tension remains: should we strive for maximal flexibility of inheritance, to improve the possibilities for later unanticipated reuse, or should we attend above all to the conceptual integrity of...

  4. Levying Inheritance Tax Now?

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Whether China should levy inheritance tax has become a hot topic of discussion. One survey about levying such a tax on high-income earners conducted by a consultancy agency of China Youth Daily shows 48.46 percent of 11,203 respondents thought it was not yet the right time while 34.03 percent of them said it was and 17.51 percent were not sure. The survey also shows 52.6 percent of the respondents thought affluent Americans’ giving of money to charity was related to inheritance tax.

  5. Inheritance, realized heritability and biochemical mechanism of acetamiprid resistance in the cotton mealybug, Phenacoccus solenopsis Tinsley (Homoptera: Pseudococcidae).

    Science.gov (United States)

    Afzal, Muhammad Babar Shahzad; Abbas, Naeem; Shad, Sarfraz Ali

    2015-07-01

    The cotton mealybug, Phenacoccus solenopsis Tinsley (Homoptera: Pseudococcidae) is a serious pest in many countries of the world because of its polyphagous nature and has caused huge losses to the cotton crop. The aim of present study was to explore the mode of inheritance and mechanism of acetamiprid resistance in P. solenopsis. After five rounds of selection with acetamiprid, P. solenopsis developed a 315-fold resistance compared with the laboratory susceptible population. The LC50 values of progenies of both reciprocal crosses (F1 and F1') showed no significant difference and degree of dominance values were 0.56 and 0.93 for F1 and F1', respectively. Monogenic model of inheritance and Lande's method revealed that more than one factors were involved in acetamiprid resistance. Realized heritability (h(2)) value was 0.58 for acetamiprid resistance. A synergism study of piperonyl butoxide (PBO) and S,S,S-tributylphosphorotrithioate (DEF) with acetamiprid also showed the significant presence of P-450 mono-oxygenase and esterase in the acetamiprid resistance. Hence, acetamiprid resistance in the P. solenopsis was autosomal, incompletely dominant and polygenic. These results are a source of basic information to design and plan fruitful management programmes to control P. solenopsis. PMID:26071806

  6. Inheritance Pattern and Clinical Aspects of 93 Iranian Patients with Chronic Granulomatous Disease

    NARCIS (Netherlands)

    Fattahi, Fatemeh; Badalzadeh, Mohsen; Sedighipour, Leyla; Movahedi, Masoud; Fazlollahi, Mohammad Reza; Mansouri, Seyed Davood; Khotaei, Ghamar Taj; Bemanian, Mohammad Hassan; Behmanesh, Fatemeh; Hamidieh, Amir Ali; Bazargan, Nasrin; Mamishi, Setareh; Zandieh, Fariborz; Chavoshzadeh, Zahra; Mohammadzadeh, Iraj; Mahdaviani, Seyed Alireza; Tabatabaei, Seyed Ahmad; Kalantari, Najmeddin; Tajik, Shaghayegh; Maddah, Marzieh; Pourpak, Zahra; Moin, Mostafa

    2011-01-01

    Chronic granulomatous disease (CGD) is a rare immunodeficiency due to a genetic defect in one of the NADPH-oxidase components. We studied CGD inheritance forms (autosomal recessive (AR) or X-linked (XL)) and AR-CGD subtypes in Iran. Clinical and functional investigations were conducted in 93 Iranian

  7. Mutations in MFSD8, encoding a lysosomal membrane protein, are associated with nonsyndromic autosomal recessive macular dystrophy

    NARCIS (Netherlands)

    Roosing, S.; Born, L.I. van den; Sangermano, R.; Banfi, S.; Koenekoop, R.K.; Zonneveld-Vrieling, M.N.; Klaver, C.C.; Lith-Verhoeven, J.J. van; Cremers, F.P.M.; Hollander, A.I. den; Hoyng, C.B.

    2015-01-01

    PURPOSE: This study aimed to identify the genetic defects in 2 families with autosomal recessive macular dystrophy with central cone involvement. DESIGN: Case series. PARTICIPANTS: Two families and a cohort of 244 individuals with various inherited maculopathies and cone disorders. METHODS: Genome-w

  8. Adaptor Protein Complex 4 Deficiency Causes Severe Autosomal-Recessive Intellectual Disability, Progressive Spastic Paraplegia, Shy Character, and Short Stature

    OpenAIRE

    Abou Jamra, Rami; Philippe, Orianne; Raas-Rothschild, Annick; Eck, Sebastian H.; Graf, Elisabeth; Buchert, Rebecca; Borck, Guntram; Ekici, Arif; Brockschmidt, Felix F.; Nöthen, Markus M.; Munnich, Arnold; Strom, Tim M.; Reis, Andre; Colleaux, Laurence

    2011-01-01

    Intellectual disability inherited in an autosomal-recessive fashion represents an important fraction of severe cognitive-dysfunction disorders. Yet, the extreme heterogeneity of these conditions markedly hampers gene identification. Here, we report on eight affected individuals who were from three consanguineous families and presented with severe intellectual disability, absent speech, shy character, stereotypic laughter, muscular hypotonia that progressed to spastic paraplegia, microcephaly,...

  9. Park7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36

    NARCIS (Netherlands)

    C.M. van Duijn (Cock); G.J. Breedveld (Guido); M. Horstink (Marten); L.A. Sandkuijl (Lodewijk); B.A. Oostra (Ben); J.C. van Swieten; V. Bonifati (Vincenzo); R-J.H. Galjaard (Robert-Jan); J.J. Houwing-Duistermaat (Jeanine); L. Testers; M.C.J. Dekker (Marieke); P.J.L.M. Snijders (Pieter); P. Heutink (Peter)

    2001-01-01

    textabstractAlthough the role of genetic factors in the origin of Parkinson disease has long been disputed, several genes involved in autosomal dominant and recessive forms of the disease have been localized. Mutations associated with early-onset autosomal recessive parkinsonism have been identified

  10. Park7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36.

    NARCIS (Netherlands)

    Duijn, C.M. van; Dekker, M.C.J.; Bonifati, V.; Galjaard, R.J.; Houwing-Duistermaat, J.J.; Snijders, P.J.L.M.; Testers, L.; Breedveld, G.J.; Horstink, M.W.I.M.; Sandkuijl, L.A.; Swieten, J. van; Oostra, B.A.; Heutink, P.

    2001-01-01

    Although the role of genetic factors in the origin of Parkinson disease has long been disputed, several genes involved in autosomal dominant and recessive forms of the disease have been localized. Mutations associated with early-onset autosomal recessive parkinsonism have been identified in the Park

  11. Principles of epigenetic inheritance

    Czech Academy of Sciences Publication Activity Database

    Vyskot, Boris

    České Budějovice, 2008. s. 11-13. ISBN 80-85645-59-9. [XXIII Genetic Days. 10.09.2008-12.09.2008, České Budějovice] R&D Projects: GA MŠk(CZ) LC06004; GA ČR(CZ) GA521/06/0056 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : epigenetics * inheritance * gene Subject RIV: BO - Biophysics

  12. Tackling Inherited Blindness

    OpenAIRE

    Batten, Matthew L.; Imanishi, Yoshikazu; Tu, Daniel C; Doan, Thuy; Zhu, Li; Pang, Jijing; Glushakova, Lyudmila; Moise, Alexander R.; Baehr, Wolfgang; Van Gelder, Russell N.; Hauswirth, William W.; Rieke, Fred; Palczewski, Krzysztof

    2005-01-01

    Background Leber congenital amaurosis (LCA), a heterogeneous early-onset retinal dystrophy, accounts for ~15% of inherited congenital blindness. One cause of LCA is loss of the enzyme lecithin:retinol acyl transferase (LRAT), which is required for regeneration of the visual photopigment in the retina. Methods and Findings An animal model of LCA, the Lrat −/− mouse, recapitulates clinical features of the human disease. Here, we report that two interventions—intraocular gene therapy and oral ph...

  13. Inheritance of intersex disorders.

    OpenAIRE

    Muram, D; Dewhurst, J

    1984-01-01

    Intersex disorders result from abnormalities of the sex chromosomes, gonads, internal and external genitalia, sex hormones and gender role. This article reviews the literature on intersex disorders, outlining the characteristics and mode of inheritance, if known, of each. For appropriate and effective management and counselling of patients and their families, physicians must have a good knowledge of the development of the genital tract and of the interaction between genetic sex and environmen...

  14. Inheritance, Realized Heritability, and Biochemical Mechanisms of Malathion Resistance in Bactrocera dorsalis (Diptera: Tephritidae).

    Science.gov (United States)

    Wang, Luo-Luo; Feng, Zi-Jiao; Li, Ting; Lu, Xue-Ping; Zhao, Jia-Jia; Niu, Jin-Zhi; Smagghe, Guy; Wang, Jin-Jun

    2016-02-01

    To better characterize the resistance development and therefore establish effective pest management strategies, this study was undertaken to investigate the inheritance mode and biochemical mechanisms of malathion resistance in the oriental fruit fly, Bactrocera dorsalis (Hendel), which is one of the most notorious pests in the world. After 22 generations of selection with malathion, the malathion-resistant (MR) strain of B. dorsalis developed a 34-fold resistance compared with a laboratory susceptible strain [malathion-susceptible (MS)]. Bioassay results showed that there was no significant difference between the LD50 values of malathion against the progenies from both reciprocal crosses (F(1)-SR and F(1)-RS). The degree of dominance values (D) was calculated as 0.39 and 0.32 for F(1)-RS and F(1)-SR, respectively. The logarithm dosage-probit mortality lines of the F(2) generation and progeny from the backcross showed no clear plateaus of mortality across a range of doses. In addition, Chi-square analysis revealed significant differences between the mortality data and the theoretical expectations. The realized heritability (h(2)) value was 0.16 in the laboratory-selected resistant strain of B. dorsalis. Enzymatic activities identified significant changes of carboxylesterases, cytochrome P450 (general oxidases), and glutathione S-transferases in MR compared with the MS strain of B. dorsalis. Taken together, this study revealed for the first time that malathion resistance in B. dorsalis follows an autosomal, incompletely dominant, and polygenic mode of inheritance and is closely associated with significantly elevated activities of three major detoxification enzymes. PMID:26362988

  15. Urine Kidney Injury Molecule-1 can Predict the Progression of Autosomal Dominant Polycystic Kidney Disease in Early Stage Patients%尿肾损伤分子-1预示常染色体显性多囊肾病早期发展速度

    Institute of Scientific and Technical Information of China (English)

    马熠熠; 陈冬平; 梅长林; 郁胜强; 李林; 徐成钢

    2011-01-01

    目的:探讨尿KIM-1水平与早期ADPKD患者病情进展的相关性,及其预示作用.方法:(1)收集临床确诊为ADPKD患者(CKD1,2期)及体检健康人群各40例,并取其晨起后第2次尿液标本,采用ELISA方法测定尿液中Kim-1浓度,比较多囊肾病人群与正常人群在Kim-1表达程度的差异;(2)用多囊肾患者肾脏体积增长速度判断疾病进展状况,用MRI肾脏成像的方法计算6个月间隔后肾脏体积增长情况;(3)去除肾脏总体积大于1 500 cm3的患者,以肾脏体积半年增长率2.7%为界,将患者划分为高平均速度组和低平均速度组,比较两组间KIM-1水平差异.结果:(1)多囊肾患者与正常人群相比,eGFR水平(采用CKD-EPI公式计算)差异无统计学意义(P>0.05),但尿中Kim-1水平多囊肾病组显著升高[(837.9±821.5) pg/ml vs (440.3±270.2) pg/ml,P<0.05];(2)多囊肾患者半年肾脏体积增长速度为(4.88±3.86)%,显著高于国外报道的多囊肾患者半年体积增长速度;(3)高平均速度组KIM-1水平高于低平均速度组(P<0.05).结论:Kim-1作为肾小管损伤后出现的一种重要的生物标记物在多囊肾病患者群中表达显著升高,能预示早期肾脏体积并未发展到一定程度的多囊肾患者肾体积的增长快慢,但Kim-1在疾病进展中的作用机制仍需要进一步的实验研究阐明.%Objective:To study the correlation between urine Kidney injury molecule - 1( KIM - 1 ) and the progression of Autosomal Dominant Polycystic Kidney Disease ( ADPKD ) in early stage patients.Methods :( 1 )Human KIM - 1 Elisa kit was used to determine the different levels of urine KIM - 1 in 40 ADPKD patients and 40 healthy individuals.All the patients were diagnosed with stage Ⅰ or stage Ⅱ chronic kidney disease at the time of enrollment.( 2 )We used the increasing rate of total kidney volume to evaluate the progression of ADPKD patients.Increases in kidney volume in ADPKD patients were detected within 6 months by

  16. The ADAMTS18 gene is responsible for autosomal recessive early onset severe retinal dystrophy

    OpenAIRE

    Peluso Ivana; Conte Ivan; Testa Francesco; Dharmalingam Gopuraja; Pizzo Mariateresa; Collin Rob WJ; Meola Nicola; Barbato Sara; Mutarelli Margherita; Ziviello Carmela; Barbarulo Anna Maria; Nigro Vincenzo; Melone Mariarosa AB; Simonelli Francesca; Banfi Sandro

    2013-01-01

    Abstract Background Inherited retinal dystrophies, including Retinitis Pigmentosa and Leber Congenital Amaurosis among others, are a group of genetically heterogeneous disorders that lead to variable degrees of visual deficits. They can be caused by mutations in over 100 genes and there is evidence for the presence of as yet unidentified genes in a significant proportion of patients. We aimed at identifying a novel gene for an autosomal recessive form of early onset severe retinal dystrophy i...

  17. Soft inheritance: challenging the modern synthesis

    Directory of Open Access Journals (Sweden)

    Eva Jablonka

    2008-01-01

    Full Text Available This paper presents some of the recent challenges to the Modern Synthesis of evolutionary theory, which has dominated evolutionary thinking for the last sixty years. The focus of the paper is the challenge of soft inheritance - the idea that variations that arise during development can be inherited. There is ample evidence showing that phenotypic variations that are independent of variations in DNA sequence, and targeted DNA changes that are guided by epigenetic control systems, are important sources of hereditary variation, and hence can contribute to evolutionary changes. Furthermore, under certain conditions, the mechanisms underlying epigenetic inheritance can also lead to saltational changes that reorganize the epigenome. These discoveries are clearly incompatible with the tenets of the Modern Synthesis, which denied any significant role for Lamarckian and saltational processes. In view of the data that support soft inheritance, as well as other challenges to the Modern Synthesis, it is concluded that that synthesis no longer offers a satisfactory theoretical framework for evolutionary biology.

  18. Inheritance of flower colour in Desmodium gangeticum (L.) DC.

    OpenAIRE

    Harshwardhan R. Nandanwar* and P. Manivel

    2014-01-01

    The present experiment was conducted with the aim to study the inheritance pattern of flower colour in Desmodium gangeticum. Populations of two parental lines having two different flower colours, white (DDG 18) and pink (DDG 8) were used for study. The results indicated that flower colour was under monogenic control of dominant gene with pink colour indicating the mendelian inheritance pattern exhibiting the monohybrid ratio of 3:1. The data was confirmed by χ2 test which showed non-significa...

  19. 运用构象敏感凝胶电泳筛查常染色体显性视网膜色素变性患者视紫红质基因突变的研究%Mutation screening of the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa with conformation-sensitive gel electrophoresis

    Institute of Scientific and Technical Information of China (English)

    张晓莉; 赵红霞; 孟晓红; 张雪; 黄军富

    2005-01-01

    目的:视网膜色素变性(retinitis pigmentosa,RP)是一组最常见的遗传性致盲眼底病.突变研究至今已证实视紫红质(rhodopsin,RHO)基因突变可导致常染色体显性遗传RP(autosomal dominant RP,ADRP),并且可能是目前ADRP最常见的病因.对27例ADRP先证者进行RHO基因突变的筛选与检测,以探明中国ADRP患者基因突变的特征和意义.方法:1999~2002年在解放军第三军医大学西南医院收集到27例ADRP家系.患者经过全面的跟科检查(包括眼底镜观察及视网膜电图?测试),RP诊断的确立依照国内外的通用标准.在27例ADRP先证者中运用构象敏感凝胶电泳(conformation sensitive gel electrophoresis,CSGE)和DNA直接测序方法检测RHO基因全编码区范围内的点突变.结果:一个ADRP家系的4名患者在第347密码子发生单碱基置换突变,Pro347Leu;另一个ADRP家系中一名晚发型患者及其目前还未出现明显症状的女儿在第327密码子出现缺失突变,Pro327(1-bp del),而对照组100例健康成年人未发现上述两种突变.结论:27例ADRP先证者中检出2例携带RHO基因突变,由此RHO基因在这组ADRP患者中的突变频率约为7.4%(2/27).Pro347Leu突变改变了视蛋白C末端一段高度保守的氨基酸序列,可能使该蛋白在胞内的运输发生障碍.Pro327(1-bp del)使突变蛋白的羧基末端失去了原有的磷酸化位点及上述一段高度保守的功能区,其可能的致病机制有待在今后的研究中通过建立相应的转基因模型或细胞培养系统来阐明.

  20. 一个常染色体显性遗传Emery-Dreifuss型肌营养不良家系的基因突变分析%Mutation analysis of a Chinese family with autosomal dominant Emery-Dreifuss muscular dystrophy

    Institute of Scientific and Technical Information of China (English)

    袁军辉; 胡静; 赵哲; 沈宏锐; 李娜; 邴琪

    2010-01-01

    Objective To investigate the clinical, pathological and genetic characteristics in a family with autosomal dominant Emery-Dreifuss muscular dystrophy (AD-EDMD). Methods Clinical data and skeletal muscle specimens were collected from two patients (the proband and her daughter) for pathological analysis. DNA samples of the proband and her family members (7 persons from 3 generations) were obtained for PCR amplification and direct DNA sequencing of the lamin A/C (LMNA) gene. Haplotype analysis was performed after the identification of mutation. Results The proband had typical clinical manifestation of EDMD: joint contracture, progressive muscle weakness and atrophy and cardiac conduction dysfunction. Muscular pathology revealed myopathic changes combined with slight neuropathic changes. A heterozygous missense mutation 1583 (C→G) (T528R) was identified in exon 9 of the LMNA gene in the two patients, but not in other family members. Haplotype analysis indicated that the proband and her daughter shared the same causative haplotype. Conclusion This is the first report of the phenotype and genotype of AD-EDMD in Chinese.%目的 探讨一个常染色体显性遗传Emery-Dreifuss型肌营养不良(Emery-Dreifuss muscular dystrophy,EDMD)家系的临床、病理及遗传学特点.方法 收集家系中2例患者(先证者及女儿)的临床资料及骨骼肌标本,行组织化学染色病理分析;收集先证者及家系成员(3代7人)血液DNA标本,采用聚合酶链反应和DNA直接测序方法 对LMNA基因进行突变检测;明确基因变异位点后对家系行单倍型分析.结果 先证者具有典型的EDMD临床表现:关节挛缩、进行性加重的肌无力和肌萎缩、心脏传导异常;骨骼肌活检病理示肌源性合并轻度神经源性改变;2例患者LMNA基因第9外显子发现杂合错义突变1583(C→G)(T528R),表型正常的其他家系成员未发现该突变;单倍型分析显示先证者及女儿具有相同的致病单倍型.结论

  1. Inherited mitochondrial disorders.

    Science.gov (United States)

    Finsterer, Josef

    2012-01-01

    Though inherited mitochondrial disorders (MIDs) are most well known for their syndromic forms, for which widely known acronyms (MELAS, MERRF, NARP, LHON etc.) have been coined, the vast majority of inherited MIDs presents in a non-syndromic form. Since MIDs are most frequently multisystem disorders already at onset or during the disease course, a MID should be suspected if there is a combination of neurological and non-neurological abnormalities. Neurological abnormalities occurring as a part of a MID include stroke-like episodes, epilepsy, migraine-like headache, movement disorders, cerebellar ataxia, visual impairment, encephalopathy, cognitive impairment, dementia, psychosis, hypopituitarism, aneurysms, or peripheral nervous system disease, such as myopathy, neuropathy, or neuronopathy. Non-neurological manifestations concern the ears, the endocrine organs, the heart, the gastrointestinal tract, the kidneys, the bone marrow, and the skin. Whenever there is an unexplained combination of neurological and non-neurological disease in a patient or kindred, a MID should be suspected and appropriate diagnostic measures initiated. Genetic testing should be guided by the phenotype, the biopsy findings, and the biochemical results. PMID:22399423

  2. Inheritance of Cytosine Methylation.

    Science.gov (United States)

    Tillo, Desiree; Mukherjee, Sanjit; Vinson, Charles

    2016-11-01

    There are numerous examples of parental transgenerational inheritance that is epigenetic. The informational molecules include RNA, chromatin modifications, and cytosine methylation. With advances in DNA sequencing technologies, the molecular and epigenetic mechanisms mediating these effects are now starting to be uncovered. This mini-review will highlight some of the examples of epigenetic inheritance, the establishment of cytosine methylation in sperm, and recent genomic studies linking sperm cytosine methylation to epigenetic effects on offspring. A recent paper examining changes in diet and sperm cytosine methylation from pools of eight animals each, found differences between a normal diet, a high fat diet, and a low protein diet. However, epivariation between individuals within a group was greater than the differences between groups obscuring any potential methylation changes linked to diet. Learning more about epivariation may help unravel the mechanisms that regulate cytosine methylation. In addition, other experimental and genetic systems may also produce more dramatic changes in the sperm methylome, making it easier to unravel potential transgenerational phenomena. J. Cell. Physiol. 231: 2346-2352, 2016. © 2016 Wiley Periodicals, Inc. PMID:26910768

  3. Genetics of the dominant ataxias

    NARCIS (Netherlands)

    Verbeek, Dineke S.; van de Warrenburg, Bart P. C.

    2011-01-01

    The relevant clinical, genetic, and cell biologic aspects of the dominantly inherited spinocerebellar ataxias (SCAs) are reviewed in this article. SCAs are diseases of the entire nervous system; in addition to cerebellar ataxia, the central (but not obligate) disease feature, many noncerebellar comp

  4. MiR-204 is responsible for inherited retinal dystrophy associated with ocular coloboma.

    Science.gov (United States)

    Conte, Ivan; Hadfield, Kristen D; Barbato, Sara; Carrella, Sabrina; Pizzo, Mariateresa; Bhat, Rajeshwari S; Carissimo, Annamaria; Karali, Marianthi; Porter, Louise F; Urquhart, Jill; Hateley, Sofie; O'Sullivan, James; Manson, Forbes D C; Neuhauss, Stephan C F; Banfi, Sandro; Black, Graeme C M

    2015-06-23

    Ocular developmental disorders, including the group classified as microphthalmia, anophthalmia, and coloboma (MAC) and inherited retinal dystrophies, collectively represent leading causes of hereditary blindness. Characterized by extreme genetic and clinical heterogeneity, the separate groups share many common genetic causes, in particular relating to pathways controlling retinal and retinal pigment epithelial maintenance. To understand these shared pathways and delineate the overlap between these groups, we investigated the genetic cause of an autosomal dominantly inherited condition of retinal dystrophy and bilateral coloboma, present in varying degrees in a large, five-generation family. By linkage analysis and exome sequencing, we identified a previously undescribed heterozygous mutation, n.37 C > T, in the seed region of microRNA-204 (miR-204), which segregates with the disease in all affected individuals. We demonstrated that this mutation determines significant alterations of miR-204 targeting capabilities via in vitro assays, including transcriptome analysis. In vivo injection, in medaka fish (Oryzias latipes), of the mutated miR-204 caused a phenotype consistent with that observed in the family, including photoreceptor alterations with reduced numbers of both cones and rods as a result of increased apoptosis, thereby confirming the pathogenic effect of the n.37 C > T mutation. Finally, knockdown assays in medaka fish demonstrated that miR-204 is necessary for normal photoreceptor function. Overall, these data highlight the importance of miR-204 in the regulation of ocular development and maintenance and provide the first evidence, to our knowledge, of its contribution to eye disease, likely through a gain-of-function mechanism. PMID:26056285

  5. Variability and inheritance of the tillering in barley hybrids

    Directory of Open Access Journals (Sweden)

    Mandić Milomirka

    2006-01-01

    Full Text Available Productive tillering is a very important trait which influences the degree of barley lodging resistance. Five dive-gent genotypes of two-rowed winter barley (Vada, Đerdap, NS-293, Jagodinac and Sladoran have been selected for diallel crossing in order to study the mode of inheritance, the gene effect and the components genetic variance for the productive tillering in F1 and F2 generation. The test of the significance of the generations' mean values related to the parental average was used for inheritance mode determinations (KRALJEVIC-BALALIC et al., 1991 and the genetic variance components and regression VrWr analysis from diallel crossings were made using the method of MATHER and JINKS (1971. The variability of the investigated trait differed. The cross combination Đerdap x Jagodinac had the highest coefficient of variance (39.78%. Different modes of inheritance (partial dominance, dominance and over dominance and partial dominance were found in the F1 and F2 generation, respectively. The genetic variance components, average degree of dominance and regression line indicated partial dominance in the inheritance of tillering. The range of the obtained values of heritability for the tillering was found to be very wide (0.02-0.47. The cross combinations Đerdap x Jagodinac and Vada x Đerdap were selected for future breeding.

  6. NEW BEST1 MUTATIONS IN AUTOSOMAL RECESSIVE BESTROPHINOPATHY

    Science.gov (United States)

    FUNG, ADRIAN T.; YZER, SUZANNE; GOLDBERG, NAOMI; WANG, HAO; NISSEN, MICHAEL; GIOVANNINI, ALFONSO; MERRIAM, JOANNA E.; BUKANOVA, ELENA N.; CAI, CAROLYN; YANNUZZI, LAWRENCE A.; TSANG, STEPHEN H.; ALLIKMETS, RANDO

    2015-01-01

    Purpose To report the ocular phenotype in patients with autosomal recessive bestrophinopathy and carriers, and to describe novel BEST1 mutations. Methods Patients with clinically suspected and subsequently genetically proven autosomal recessive bestrophinopathy underwent full ophthalmic examination and investigation with fundus autofluorescence imaging, spectral domain optical coherence tomography, electroretinography, and electrooculography. Mutation analysis of the BEST1 gene was performed through direct Sanger sequencing. Results Five affected patients from four families were identified. Mean age was 16 years (range, 6–42 years). All affected patients presented with reduced visual acuity and bilateral, hyperautofluorescent subretinal yellowish deposits within the posterior pole. Spectral domain optical coherence tomography demonstrated submacular fluid and subretinal vitelliform material in all patients. A cystoid maculopathy was seen in all but one patient. In 1 patient, the location of the vitelliform material was seen to change over a follow-up period of 3 years despite relatively stable vision. Visual acuity and fundus changes were unresponsive to topical and systemic carbonic anhydrase inhibitors and systemic steroids. Carriers had normal ocular examinations including normal fundus autofluorescence. Three novel mutations were detected. Conclusion Three novel BEST1 mutations are described, suggesting that many deleterious variants in BEST1 resulting in haploinsufficiency are still unknown. Mutations causing autosomal recessive bestrophinopathy are mostly located outside of the exons that usually harbor vitelliform macular dystrophy–associated dominant mutations. PMID:25545482

  7. Autosomal recessive polycystic kidney disease. A case report.

    Directory of Open Access Journals (Sweden)

    Hernando Diocaretz V

    2015-01-01

    Full Text Available INTRODUCTION: Polycystic Kidney Disease is a genetic disorder characterized by progressive cystic dilations of the renal ducts, presenting as autosomal dominant or recessive forms with an incidence of 1 in 1.000 and 1 in 20.000 births, respectively, according to international series. The autosomal recessive variety can be lethal in the neonatal period due to respiratory failure secondary to pulmonary hypoplasia and can manifest during childhood with hypertension, short stature and complications of portal hypertension. CASE REPORT: 3 years and 11 months old preschoolar with antecedent of fetal growth restriction and oligohydramnios during prenatal period, and a history of asthenia, pallor and progressive feeding difficulty with postprandial vomiting. Physical examination shows cardiac bruit, hypertension, splenomegaly, caput medusae and short stature. Laboratory tests with peripheral pancytopenia; abdominal ultrasonography showed hepatosplenomegaly, findings consistent with autosomal recessive polycystic kidney disease and periportal fibrosis; renal scintigraphy with bilateral kidney failure; a positive fecal occult blood test; an upper endoscopy that shows small esophageal varices; a hand radiography that shows bone age delayed and an echocardiography with cardiomegaly. DISCUSSION: This infrequent disease requires a high degree of suspicion by the clinician and presents with portal hypertension, with platelet count being the best predictor of severity. This condition has no cure and will progress to end-stage renal disease in any moment, so the aim is to minimize and treat renal and hepatic complications.

  8. A new autosomal recessive disorder of bilateral frontotemporal pachygyria without microcephaly: Report of a case and review of literature

    Directory of Open Access Journals (Sweden)

    Phadke Shubha

    2007-01-01

    Full Text Available Pachygyria is a disorder of neuronal migration. We report an Indian family with four siblings with developmental delay, infrequent seizures, normal head size and mild to moderate mental retardation. Two of them had bilaterally symmetrical frontotemporal pachygyria. Dysmorphism and neurological signs were absent in the affected subjects. Affected male and female siblings with normal parents suggests autosomal recessive mode of inheritance. We believe these cases represent a new autosomal recessive disorder of neuronal migration. Other similar cases of lissencephaly are reviewed.

  9. 汉族常染色体显性视网膜色素变性一家系的连锁分析及突变筛查%Linkage analysis and mutation screening of candidate gene in a Han Nationality family with autosomal dominant retinitis pigmentosa

    Institute of Scientific and Technical Information of China (English)

    张进; 严明; 宋贵波; 郑芳

    2012-01-01

    背景 原发性视网膜色素变性(RP)有明显的遗传异质性和表型异质性,目前已确定的致病基因较多,确定患病家系的致病基因是进行基因治疗的基础. 目的 对患常染色体显性遗传性RP(ADRP)的一个汉族家系进行致病基因的定位和基因突变分析.方法 此家系的5代21名成员纳入研究,包括12例ADRP患者和9名表型正常者.12例患者进一步接受中心视野、间接检眼镜、眼电图(EOG)、视网膜电图(ERG)检查.对22个已知的ADRP致病基因所在染色体位点进行连锁分析,以确定该家系与疾病连锁的染色体区域,随后对该区域附近的候选基因视紫红质(RHO)进行直接测序评估其突变情况. 结果 间接检眼镜检查该家系先证者眼底表现符合原发性RP表现,EOG和ERG表现为波形记录不到,视野呈向心性缩小.两点连锁分析结果显示,该家系致病基因位点与遗传标记D3S1292连锁,在θ=0.0时得到最大优势对数(LOD)值为3.6671.候选的RHO基因直接测序结果发现,该家系所有患者第53位密码子的第2个核苷酸均出现了C→G的突变,致其氨基酸由脯氨酸变为精氨酸(Pro53Arg),而该家系正常成员中未发现此突变. 结论 RHO基因的错义突变Pro53Arg与RP疾病出现共分离现象,可确定为该ADRP家系的致病基因.%Background Retinitis pigmentosa (RP) has the genetic and phenotype heterogeneity.To determine the disease-causing gene is a foundation of gene therapy. Objective This study was to localize the pathogenic gene and screen the gene mutation associated with Han Nationality autosomal dominant retinitis pigmentosa (ADRP) in a Chinese family. Methods Twenty-one families enrolled this study,including 12 patients with ADRP and 9 individuals with normal phenotype.Perimetry,fundus examination,electrooculogram ( EOG ) and electroretinogram (ERG) were performed in 12 patients.Genetic linkage analysis was performed on the subjects in all known genetic loci

  10. A retrospective study on management of gross hematuria in autosomal dominant polycystic kidney disease patients%常染色体显性多囊肾病患者并发肉眼血尿治疗方法的回顾研究

    Institute of Scientific and Technical Information of China (English)

    马熠熠; 陈冬平; 梅长林; 郁胜强; 戎殳; 张彤; 李林

    2012-01-01

    目的 寻找治疗常染色体显性多囊肾病(ADPKD)并发肉眼血尿的理想疗法.方法 1993年以来曾在我科住院治疗以及目前在我科多囊肾病专科门诊定期就诊随访的ADPKD患者为对象.收集ADPKD患者出现肉眼血尿时的平均年龄、性别构成、肾功能水平、诱发因素、治疗方案、症状持续时间、血小板计数、凝血参数、肾脏囊肿大小等资料,分别以不同的肉眼血尿诱发因素及治疗方案进行分组,比较其各指标间的差异.结果 共筛选出ADPKD患者905例.279例(男150例,女129例)曾有肉眼血尿病史,其中146例能提供完整的病史和治疗经过,而只有101例能提供相关的实验室检查结果.在这101例中,肉眼血尿可出现在慢性肾脏病(CKD)任何一期;GFR为(56.4±44.1)ml·min-1·(1.73 m2)-1;症状持续时间(8.8±8.0)d;男、女患者症状持续时间差异无统计学意义[(8.2±7.3)d比(9.5±8.8)d,P=0.426);凝血参数均在正常参考范围内,其中91例患者血小板计数正常.不同诱发因素导致的肉眼血尿持续时间差异有统计学意义(P<0.05).卧床休息组症状持续时间显著短于其他组患者(P<0.05).各组间血小板计数、凝血酶时间和国际标准化比值等差异无统计学意义.结论 对出现肉眼血尿的ADPKD患者应首先明确其诱因.卧床休息应作为核心治疗措施.在考虑使用止血药物时建议使用抗纤维蛋白溶解类药物,不需要预防性使用抗生索.%Objective To seauch the ideal management for gross hematuria in autosomal dominant polycystic kidney disease (ADPKD).Methods ADPKD patients who were ever hospitalized and followed up in our department since 1993 were enrolled in the study.Demographic and clinical data were colloected,such as gender,age of gross hematuria,level of renal function,causative factors,management strategies,duration of gross hematuria,blood platelet count,activated partial thromboplastin time,prothrombin time

  11. Inherited epidermolysis bullosa

    Directory of Open Access Journals (Sweden)

    Fine Jo-David

    2010-05-01

    Full Text Available Abstract Inherited epidermolysis bullosa (EB encompasses a number of disorders characterized by recurrent blister formation as the result of structural fragility within the skin and selected other tissues. All types and subtypes of EB are rare; the overall incidence and prevalence of the disease within the United States is approximately 19 per one million live births and 8 per one million population, respectively. Clinical manifestations range widely, from localized blistering of the hands and feet to generalized blistering of the skin and oral cavity, and injury to many internal organs. Each EB subtype is known to arise from mutations within the genes encoding for several different proteins, each of which is intimately involved in the maintenance of keratinocyte structural stability or adhesion of the keratinocyte to the underlying dermis. EB is best diagnosed and subclassified by the collective findings obtained via detailed personal and family history, in concert with the results of immunofluorescence antigenic mapping, transmission electron microscopy, and in some cases, by DNA analysis. Optimal patient management requires a multidisciplinary approach, and revolves around the protection of susceptible tissues against trauma, use of sophisticated wound care dressings, aggressive nutritional support, and early medical or surgical interventions to correct whenever possible the extracutaneous complications. Prognosis varies considerably and is based on both EB subtype and the overall health of the patient.

  12. Phenotype as Agent for Epigenetic Inheritance.

    Science.gov (United States)

    Torday, John S; Miller, William B

    2016-01-01

    The conventional understanding of phenotype is as a derivative of descent with modification through Darwinian random mutation and natural selection. Recent research has revealed Lamarckian inheritance as a major transgenerational mechanism for environmental action on genomes whose extent is determined, in significant part, by germ line cells during meiosis and subsequent stages of embryological development. In consequence, the role of phenotype can productively be reconsidered. The possibility that phenotype is directed towards the effective acquisition of epigenetic marks in consistent reciprocation with the environment during the life cycle of an organism is explored. It is proposed that phenotype is an active agent in niche construction for the active acquisition of epigenetic marks as a dominant evolutionary mechanism rather than a consequence of Darwinian selection towards reproductive success. The reproductive phase of the life cycle can then be appraised as a robust framework in which epigenetic inheritance is entrained to affect growth and development in continued reciprocal responsiveness to environmental stresses. Furthermore, as first principles of physiology determine the limits of epigenetic inheritance, a coherent justification can thereby be provided for the obligate return of all multicellular eukaryotes to the unicellular state. PMID:27399791

  13. Genetics Home Reference: autosomal recessive hypotrichosis

    Science.gov (United States)

    ... Autosomal recessive hypotrichosis is a condition that affects hair growth. People with this condition have sparse hair ( hypotrichosis ) ... erosions) on the scalp. In areas of poor hair growth, they may also develop bumps called hyperkeratotic follicular ...

  14. A Register-Based Study of Diseases With an Autosomal Recessive Origin in Small Children in Denmark According to Maternal Country of Origin

    DEFF Research Database (Denmark)

    Gundlund, Anna; Hansen, Anne Vinkel; Pedersen, Grete Skøtt;

    2015-01-01

    information on consanguinity is lacking, this suggestion is difficult to test. With an indirect approach, we addressed this question by comparing the risk of diseases with autosomal recessive inheritance in children born in Denmark of Danish-born women and of women born in these five countries, respectively...

  15. 一汉族常染色体显性遗传视网膜色素变性家系视紫红质基因检测分析%Detection and analysis of the Rhodopsin gene in a consanguineous Chinese Han autosomal dominant retinitis pigmentosa family

    Institute of Scientific and Technical Information of China (English)

    陈雪娟; 高翔; 赵晨; 赵堪兴

    2013-01-01

    白折叠错误,发生ERS.%Background Rhodopsin (RHO) gene is the most common disease gene for autosomal dominant retinitis pigmentosa (adRP),one of the main pathogenesis is that misfolded mutant RHO proteins accumulate in the endoplasmic reticulum and cause endoplasmic reticulum stress (ERS).Objective This study aimed to determine the genetic basis for a consanguineous Chinese Han adRP family.Methods This study procedure complied with Helsinki Declaration.All participants in the family were investigated under the informed consent.Regular ocular examination was performed on the patients in this family.Next-generation sequencing (NGS) was carried out to screen the mutations in 189 genes associated with hereditary retinal diseases (HRDs).After being analyzed and filtered,variations detected by NGS were validated by Sanger sequencing and evaluating of pathogenicity.The wild-type RHOWT and mutant RHOP53Rwere cloned into the vector pEGFP-N1.Then the two plasmids were transfected into adult retinal pigmentosa epithelium cell line(ARPE19) and human embryo kidney 293 line (HEK293) to observe the location of rhodopsin-GFP fusion protein in cells,and the expression of ERS related protein XBP1 in the cells was detected by quantitative-PCR and Western blot.Results This family included 5 generations with the typical adRP characteristics.Genetic analysis identified a heterozygous variation,p.P53R in RHO gene,which was fully cosegregated in the family.Wild-type RHOWT-GFP fusion proteins showed the green fluorescence on the endoplasmic reticulum and cytomembrane,but the misfolded mutant RHO-GFP fusion protein gathered only in endoplasmic reticulum.Compared to wild-type RHOWT,the XBP1 was activated and increased by (1.28 ±0.09) fold.The introns of 26 bases in XBP1 mRNA were removed in the HEK293 cells with mutant RHO-GFP fusion protein,and the expression of XBP1 was stronger in the HEK293 cells with mutant RHO-GFP than that in HEK293 cells with wild type RHO-GFP and cells with blank pEGFP-N1 plasmid.Conclusions Heterozygous

  16. Multilocus Inherited Neoplasia Alleles Syndrome

    DEFF Research Database (Denmark)

    Whitworth, James; Skytte, Anne-Bine; Sunde, Lone; Lim, Derek H; Arends, Mark J; Happerfield, Lisa; Frayling, Ian M; van Minkelen, Rick; Woodward, Emma R; Tischkowitz, Marc D; Maher, Eamonn R

    Mendelian causes of inherited cancer susceptibility are mostly rare and characterized by variable expression and incomplete penetrance. Phenotypic variability may result from a range of causes including locus heterogeneity, allelic heterogeneity, genetic and environmental modifier effects, or...... chance. Another potential cause is the presence of 2 or more inherited cancer predisposition alleles in the same individual. Although the frequency of such occurrences might be predicted to be low, such cases have probably been underascertained because standard clinical practice has been to test...... candidate inherited cancer genes sequentially until a pathogenic mutation is detected. However, recent advances in next-generation sequencing technologies now provide the opportunity to perform simultaneous parallel testing of large numbers of inherited cancer genes. Herein we provide examples of patients...

  17. Autosomal recessive chronic granulomatous disease caused by deletion at a dinucleotide repeat

    International Nuclear Information System (INIS)

    Chronic granulomatous disease (CGD) is a rare inherited condition rendering neutrophils incapable of killing invading pathogens. This condition is due to the failure of a multicomponent microbicidal oxidase that normally yields a low-midpoint-potential b cytochrome (cytochrome b245). Although defects in the X chromosome-linked cytochrome account for the majority of CGD patients, as many as 30% of CGD cases are due to an autosomal recessive disease. Of these, >90% have been shown to be defective in the synthesis of a 47-kDa cytosolic component of the oxidase. The authors demonstrate here in three unrelated cases of autosomal recessive CGD that the identical underlying molecular lesion is a dinucleotide deletion at a GTGT tandem repeat, corresponding to the acceptor site of the first intron - exon junction. Slippage of the DNA duplex at this site may contribute to the high frequency of defects in this gene

  18. Northern epilepsy syndrome: an inherited childhood onset epilepsy with associated mental deterioration.

    OpenAIRE

    Hirvasniemi, A; Lang, H; Lehesjoki, A E; Leisti, J

    1994-01-01

    A new autosomal recessively inherited disease of the central nervous system involving childhood epilepsy and mental deterioration is described. Twenty three patients (11 males and 12 females) belonging to 11 families from northern Finland have been identified. A common ancestor has been found for nine families. The mean age of onset of epilepsy was 6.7 years (range 5-10 years) and the epilepsy was characterised by generalised tonic-clonic seizures increasing in frequency up to puberty. One th...

  19. Identification of two novel mutations in CDHR1 in consanguineous Spanish families with autosomal recessive retinal dystrophy

    OpenAIRE

    Konstantinos Nikopoulos; Almudena Avila-Fernandez; Marta Corton; Maria Isabel Lopez-Molina; Raquel Perez-Carro; Lara Bontadelli; Silvio Alessandro Di Gioia; Olga Zurita; Blanca Garcia-Sandoval; Carlo Rivolta; Carmen Ayuso

    2015-01-01

    Inherited retinal dystrophies present extensive phenotypic and genetic heterogeneity, posing a challenge for patients’ molecular and clinical diagnoses. In this study, we wanted to clinically characterize and investigate the molecular etiology of an atypical form of autosomal recessive retinal dystrophy in two consanguineous Spanish families. Affected members of the respective families exhibited an array of clinical features including reduced visual acuity, photophobia, defective color vision...

  20. Connexin 26 and autosomal recessive non-syndromic hearing loss

    Directory of Open Access Journals (Sweden)

    Mukherjee Monisha

    2003-01-01

    Full Text Available Prelingual deafness occurs with a frequency of 1 in 1000 live births and is divided into syndromic and non-syndromic forms contributing 40 and 60% respectively. Autosomal recessive non-syndromic hearing loss (ARNSHL is responsible for 80% cases of childhood deafness. Nearly all genes localized for ARNSHL cause prelingual, severe to profound, sensorineural hearing impairment. ARNSHL is genetically heterogeneous and at least 39 loci have been identified. The most significant finding to date has been the discovery of mutations in GJB2 gene at the DFNB1 locus on chromosome 13q12 as the major cause of profound prelingual deafness. This was first reported in a Tunisian family in 1994 and thereafter in many different countries. GJB2 gene encodes the gap-junction protein, connexin 26 (Cx26, mutations in which have become the first genetic marker of inherited hearing loss. Allele-specific polymerase chain reaction (AS-PCR, single stranded conformation polymorphism (SSCP and sequencing methods have been developed for the detection of mutations in Cx26 gene. In India as well, the Cx26 mutations are being screened in families with hearing impaired children using these molecular methods. Therefore, in order to create awareness among the clinicians and the affected families; we have attempted to review the Cx26 gene mutations responsible for autosomal recessive type of non-syndromic hearing loss. The efficacy and utility of Cx26 gene analysis might open the path to proper counseling of families for carrier detection and prenatal diagnosis. It may even facilitate the development of strategies in future for the treatment of this common genetic disorder.

  1. Genetic linkage studies in autosomal recessive retinitis pigmentosa

    Energy Technology Data Exchange (ETDEWEB)

    Mansfield, D.C.; Teague, P.W.; Barber, A. [Western General Hospital, Edinburgh (United Kingdom)] [and others

    1994-09-01

    Autosomal recessive retinitis pigmentosa (arRP) is a severe retinal dystrophy characterized by night blindness, progressive constriction of the visual fields and loss of central vision in the fourth or fifth decades. The frequency of this form of retinitis pigmentosa (RP) varies in different populations. Mutations within the rhodopsin, cyclic GMP phosphodiesterase-{beta} subunit and cGMP-gated channel genes have been reported in some arRP families. The genetic loci responsible for the majority of cases have yet to be identified. Genetic heterogeneity is likely to be extensive. In order to minimize the amount of genetic heterogenity, a set of arRP families was ascertained within the South-Central Sardinian population, in which 81% of families with a known mode of inheritance show an autosomal recessive form of RP. The Sardinian population is an ethnic {open_quotes}outlier{close_quotes}, having remained relatively isolated from mainland and other cultures. Genetic linkage data has been obtained in a set of 11 Sardinian arRP kindreds containing 26 affected members. Under the assumption of genetic homogeneity, no evidence of linkage was found in the arRP kindreds using 195 markers, which excluded 62% of the genome (Z<-2). Positive lod scores were obtained with D14S80 which showed no recombination in a subset of 5 families. Heterogeneity testing using D14S80 and arRP showed no significant evidence of heterogeneity (p=0.18) but evidence of linkage ({chi}{sup 2}=3.64, p=0.028). We are currently screening the neural retina-specific leucine zipper gene (NRL) in 14q11 for mutations as a candidate locus.

  2. Clinical and Electrophysiological Studies of a Family with Probable X-linked Dominant Charcot-Marie-Tooth Neuropathy and Ptosis.

    Directory of Open Access Journals (Sweden)

    Tony Wu

    2004-07-01

    Full Text Available Background: The X-linked dominant Charcot-Marie-Tooth neuropathy (CMTX is ahereditary motor and sensory neuropathy linked to a variety of mutations inthe connexin32 (Cx32 gene. Clinical and genetic features of CMTX havenot previously been reported in Taiwanese.Methods: Clinical evaluations and electrophysiological studies were carried out on 25family members of a Taiwanese family group. Molecular genetic analysis ofthe Cx32 gene was performed. A sural nerve biopsy was obtained from 1patient.Results: Nine patients had clinical features of X-linked dominant inheritance and amoderate Charcot-Marie-Tooth (CMT neuropathy phenotype. Moleculargenetic analysis showed no mutation of the Cx32 coding region, but revealeda G-to-A transition at position -215 of the nerve-specific promoter P2 of theCx32 gene. Ptosis is 1 clinical manifestation of neuropathy in this probableCMTX family. Familial hyperthyroidism is an additional independent featureof the family. Electrophysiological and histological studies showed featuresof axonal neuropathy. Multimodality evoked potential studies revealed normalcentral motor and sensory conduction velocities.Conclusions: The presence of ptosis in this family illustrates the existence of clinical heterogeneityamong related family members with CMTX similar to that inCMT of autosomal inheritance. Electrophysiological and histological findingsrevealed normal central conduction and axonal neuropathy.

  3. Park7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36

    OpenAIRE

    Duijn, Cock; Breedveld, Guido; Horstink, Marten; Sandkuijl, Lodewijk; Oostra, Ben; Swieten, J. C.; Bonifati, Vincenzo; Galjaard, Robert-Jan; Houwing-Duistermaat, Jeanine; Testers, L.; Dekker, Marieke; Snijders, Pieter; Heutink, Peter

    2001-01-01

    textabstractAlthough the role of genetic factors in the origin of Parkinson disease has long been disputed, several genes involved in autosomal dominant and recessive forms of the disease have been localized. Mutations associated with early-onset autosomal recessive parkinsonism have been identified in the Parkin gene, and recently a second gene, PARK6, involved in early-onset recessive parkinsonism was localized on chromosome 1p35-36. We identified a family segregating early-onset parkinsoni...

  4. Orofacial Manifestations of Autosomal Recessive Robinow’s Syndrome: A Rare Case Report

    Science.gov (United States)

    Mali, Santosh; Dhokar, Amol; Yadav, Monica

    2016-01-01

    Robinow’s syndrome is a very rare genetic disorder which bears a resemblance to a foetal face. It is characterized by short-limbed dwarfism, defects in vertebral segmentation and abnormalities in the head, face and external genitalia. It has a genetic heterogeneity with autosomal dominant and recessive forms which relates to the severity of phenotype presentation. A rare case of an autosomal recessive form of Robinow’s syndrome is presented with emphasis on, characteristic craniofacial and intraoral manifestations to aid in diagnosis and dental management of this patient.

  5. Autosomal recessive osteopetrosis in Arab children.

    Science.gov (United States)

    Abdel-Al, Y K; Shabani, I S; Lubani, M M; al-Ghawabi, M A; Ibrahim, M D; al-Mohtaseb, S; Duodin, K I

    1994-01-01

    Nineteen Arab children including six boys and 13 girls in ten sibships were diagnosed as having osteopetrosis over a 5-year period in various hospitals in Kuwait. Eighteen patients had an isolated autosomal recessive form and one had autosomal recessive osteopetrosis associated with renal tubular acidosis. The mean age of diagnosis was 24 months. Parental consanguinity was high amongst them (68%). Anaemia, hepatosplenomegaly, failure to thrive, recurrent infections and neurological manifestations were common. Associated congenital abnormalities were found in 26%. Deafness, hydrocephalus and dental caries were relatively less common. A high mortality (37%) owing to infection was noted. The medical management and recommendations for patient care are discussed briefly. PMID:7516136

  6. Inheritance of flower colour in Desmodium gangeticum (L. DC.

    Directory of Open Access Journals (Sweden)

    Harshwardhan R. Nandanwar* and P. Manivel

    2014-06-01

    Full Text Available The present experiment was conducted with the aim to study the inheritance pattern of flower colour in Desmodium gangeticum. Populations of two parental lines having two different flower colours, white (DDG 18 and pink (DDG 8 were used for study. The results indicated that flower colour was under monogenic control of dominant gene with pink colour indicating the mendelian inheritance pattern exhibiting the monohybrid ratio of 3:1. The data was confirmed by χ2 test which showed non-significant chi-square value for flower colour.

  7. Inheritance of enlarged leaf mutations in pea (Pisum sativum L.)

    International Nuclear Information System (INIS)

    In the present study, two pea (Pisum sativum L.) mutants experimentally obtained after gamma irradiation of dry seeds are described. Both mutants were characterized by enlarged leaf size. The mutant 2/462 was shown to have semi-dominant inheritance pattern; 2/927 was sterile and inherited monogenic recessive. The induced mutations have pleiotropic effect, affecting morphological and reproductive traits. New mutants had similar phenotypes to previously named mutants latifolium (lat) and cabbage leaf (calf), but no allelism tests were made between the new and the previously reported mutants. Both mutant lines may be useful plant material for research on leaf development

  8. Terapia gênica em distrofias hereditárias de retina Gene therapy for inherited retinal dystrophies

    Directory of Open Access Journals (Sweden)

    Monique Côco

    2009-08-01

    Full Text Available As distrofias hereditárias de retina abrangem um amplo número de doenças caracterizadas por lenta e progressiva degeneração da retina. São o resultado de mutações em genes expressos em fotorreceptores e no epitélio pigmentado da retina. A herança pode ser autossômica dominante, autossômica recessiva, ligada ao X recessiva, digênica ou herança mitocondrial. Atualmente não há tratamento para essas doenças e os pacientes convivem com a perda progressiva da visão. O aconselhamento genético e o suporte para reabilitação têm indicação nestes casos. Pesquisas envolvendo a base molecular e genética dessas doenças está continuamente em expansão e ampliam as perspectivas para novas formas de tratamento. Dessa forma, a terapia gênica, que consiste na inserção de material genético exógeno em células de um indivíduo com finalidade terapêutica, tem sido a principal forma de tratamento para as distrofias hereditárias de retina. O olho é um órgão peculiar para a terapia gênica, pois é anatomicamente dividido em compartimentos, imunologicamente privilegiado e com meios transparentes. A maioria das doenças oculares tem defeitos em genes conhecidos. Além disso, há modelo animal bem caracterizado para algumas condições. Propostas para pesquisa clínica em terapia gênica nas degenerações retinianas hereditárias com defeito no gene RPE65, recentemente tiveram aprovação ética e os resultados preliminares obtidos trouxeram grandes expectativas na melhora da qualidade de vida dos pacientes.The inherited retinal dystrophies comprise a large number of disorders characterized by a slow and progressive retinal degeneration. They are the result of mutations in genes that express in either the photoreceptor cells or the retinal pigment epithelium. The mode of inheritance can be autosomal dominant, autosomal recessive, X linked recessive, digenic or mitochondrial DNA inherited. At the moment, there is no treatment for these

  9. From Neo-Darwinism to Epigenetic Inheritance

    OpenAIRE

    Axholm, Ida; Ranum, Kasper; Al-Makdisi Razeeghi, Redaa

    2014-01-01

    Transgenerational epigenetic inheritance is at variance with the neo-Darwinian theory of inheritance, and this possibly has important implications for how we view evolution, since it could allow for a kind of inheritance of acquired characteristics. We have applied Imre Lakatos and Thomas Kuhn’s models of scientific change and investigated if they can accurately describe the change in the view on inheritance from neo-Darwinism to a view that includes transgenerational epigenetic inheritance, ...

  10. Inherited thrombophilia and reproductive disorders

    Science.gov (United States)

    Liatsikos, Spyros A.; Tsikouras, Panagiotis; Manav, Bachar; Csorba, Roland; von Tempelhoff, Georg Friedrich; Galazios, Georgios

    2016-01-01

    Apart from its established role in the pathogenesis of venous thromboembolism (VTE), inherited thrombophilia has been proposed as a possible cause of pregnancy loss and vascular gestational complications. There is a lot of controversy in the literature on the relationship between inherited prothrombotic defects and these obstetric complications. This is a review of the literature on inherited thrombophilia and reproductive disorders. Factor V Leiden, prothrombin G20210A mutation, and protein S deficiency seem to be associated with late and recurrent early pregnancy loss, while their impact on other pregnancy complications is conflicting. No definite association has been established between protein C and antithrombin deficiency and adverse pregnancy outcome, primarily due to their low prevalence. Screening is suggested only for women with early recurrent loss or late pregnancy loss. Anticoagulant treatment during pregnancy should be considered for women with complications who were tested positive for thrombophilia. PMID:27026779

  11. Autosomal recessive multiple pterygium syndrome: a new variant?

    Science.gov (United States)

    Aslan, Y; Erduran, E; Kutlu, N

    2000-07-31

    Multiple pterygium syndromes include at least 15 different entities characterized by multiple pterygia or webs of the skin and multiple congenital anomalies. We describe a female infant who presented with a distinct constellation of multiple anomalies consisting of pterygia of the inguinal, intercrural and popliteal areas, flexion contractures and arthrogryposis of some joints, craniofacial anomalies including ectropion, medial canthal web, blepharophimosis, hypoplasia of nose, oral and nasopharyngeal cavities, vocal cords and tongue, micrognathia, orolabial synechiae secondary to pterygia, low set ears, alopecia, sad and expressionless face, short neck, asymmetric nipples, anal stenosis, rectal polyp, hypoplastic labia majora, complete syndactyly of all fingers and toes, pes equinovarus, bandlike web between feet, and absence of the nails and phalangeal-palmar creases. Radiological examination showed synostosis, absence or hypoplasia of metacarpal, metatarsal and phalangeal bones on feet and hands, and hypoplasia of pelvic bones and scapulae. This pattern of anomalies does not fit entirely any of the known multiple pterygium syndromes. Autosomal recessive inheritance is most likely due to the presence of three similarly affected siblings and normal parents. PMID:10925380

  12. The inheritance of groin hernia

    DEFF Research Database (Denmark)

    Burcharth, J; Pommergaard, H C; Rosenberg, Jacob

    2013-01-01

    Groin hernia has been proposed to be hereditary; however, a clear hereditary pattern has not been established yet. The purpose of this review was to analyze studies evaluating family history and inheritance patterns and to investigate the possible heredity of groin hernias.......Groin hernia has been proposed to be hereditary; however, a clear hereditary pattern has not been established yet. The purpose of this review was to analyze studies evaluating family history and inheritance patterns and to investigate the possible heredity of groin hernias....

  13. Mechanisms of inherited cancer susceptibility

    Institute of Scientific and Technical Information of China (English)

    Shirley HODGSON

    2008-01-01

    A small proportion of many cancers are due to inherited mutations in genes, which result in a high risk to the individual of developing specific cancers. There are several classes of genes that may be involved: tumour suppressor genes, oncogenes, genes encoding proteins involved in DNA repair and cell cycle control, and genes involved in stimulating the angiogenic pathway. Alterations in susceptibility to cancer may also be due to variations in genes involved in carcinogen metabolism. This review discusses examples of some of these genes and the associated clinical conditions caused by the inheritance of mutations in such genes.

  14. Compound heterozygosity for a dominant glycine substitution and a recessive internal duplication mutation in the type XVII collagen gene results in junctional epidermolysis bullosa and abnormal dentition.

    Science.gov (United States)

    McGrath, J A; Gatalica, B; Li, K; Dunnill, M G; McMillan, J R; Christiano, A M; Eady, R A; Uitto, J

    1996-06-01

    Junctional epidermolysis bullosa is a heterogeneous autosomal recessively inherited blistering skin disorder associated with fragility at the dermal-epidermal junction. Previously, mutations in this condition have been described in the three genes for the anchoring filament protein laminin 5 (LAMA3, LAMB3, and LAMC2), in the gene encoding the hemidesmosome-associated beta4 integrin (ITGB4), and in the gene for the hemidesmosomal protein type XVII collagen (COL17A1/BPAG2). In this study, we report a patient with a form of junctional epidermolysis bullosa with skin fragility and dental anomalies who is a compound heterozygote for a novel combination of mutations, ie, a glycine substitution mutation in one allele and an internal duplication in the other allele of COL17A1. The patient also has two offspring, both of whom have inherited the glycine substitution mutation, whereas the other COL17A1 allele is normal. The latter individuals show no evidence of skin fragility but have marked dental abnormalities with enamel hypoplasia and pitting. The clinical phenotype of junctional epidermolysis bullosa in the proband in this family probably arises due to a combination of the glycine substitution and the internal duplication in COL17A1, whereas the dental abnormalities of her offspring may be the result of the glycine substitution in COL17A1 alone, resulting in this dominantly inherited clinical phenotype. PMID:8669466

  15. Using default inheritance to describe LTAG

    CERN Document Server

    Evans, R; Weir, D; Evans, Roger; Gazdar, Gerald; Weir, David

    1995-01-01

    We present the results of an investigation into how the set of elementary trees of a Lexicalized Tree Adjoining Grammar can be represented in the lexical knowledge representation language DATR (Evans & Gazdar 1989a,b). The LTAG under consideration is based on the one described in Abeille et al. (1990). Our approach is similar to that of Vijay-Shanker & Schabes (1992) in that we formulate an inheritance hierarchy that efficiently encodes the elementary trees. However, rather than creating a new representation formalism for this task, we employ techniques of established utility in other lexically-oriented frameworks. In particular, we show how DATR's default mechanism can be used to eliminate the need for a non-immediate dominance relation in the descriptions of the surface LTAG entries. This allows us to embed the tree structures in the feature theory in a manner reminiscent of HPSG subcategorisation frames, and hence express lexical rules as relations over feature structures.

  16. Germline loss-of-function mutations in LZTR1 predispose to an inherited disorder of multiple schwannomas.

    Science.gov (United States)

    Piotrowski, Arkadiusz; Xie, Jing; Liu, Ying F; Poplawski, Andrzej B; Gomes, Alicia R; Madanecki, Piotr; Fu, Chuanhua; Crowley, Michael R; Crossman, David K; Armstrong, Linlea; Babovic-Vuksanovic, Dusica; Bergner, Amanda; Blakeley, Jaishri O; Blumenthal, Andrea L; Daniels, Molly S; Feit, Howard; Gardner, Kathy; Hurst, Stephanie; Kobelka, Christine; Lee, Chung; Nagy, Rebecca; Rauen, Katherine A; Slopis, John M; Suwannarat, Pim; Westman, Judith A; Zanko, Andrea; Korf, Bruce R; Messiaen, Ludwine M

    2014-02-01

    Constitutional SMARCB1 mutations at 22q11.23 have been found in ∼50% of familial and schwannomatosis cases. We sequenced highly conserved regions along 22q from eight individuals with schwannomatosis whose schwannomas involved somatic loss of one copy of 22q, encompassing SMARCB1 and NF2, with a different somatic mutation of the other NF2 allele in every schwannoma but no mutation of the remaining SMARCB1 allele in blood and tumor samples. LZTR1 germline mutations were identified in seven of the eight cases. LZTR1 sequencing in 12 further cases with the same molecular signature identified 9 additional germline mutations. Loss of heterozygosity with retention of an LZTR1 mutation was present in all 25 schwannomas studied. Mutations segregated with disease in all available affected first-degree relatives, although four asymptomatic parents also carried an LZTR1 mutation. Our findings identify LZTR1 as a gene predisposing to an autosomal dominant inherited disorder of multiple schwannomas in ∼80% of 22q-related schwannomatosis cases lacking mutation in SMARCB1. PMID:24362817

  17. Genetics Home Reference: autosomal recessive cerebellar ataxia type 1

    Science.gov (United States)

    ... Genetics Home Health Conditions ARCA1 autosomal recessive cerebellar ataxia type 1 Enable Javascript to view the expand/ ... Open All Close All Description Autosomal recessive cerebellar ataxia type 1 ( ARCA1 ) is a condition characterized by ...

  18. Graded Dominance

    Czech Academy of Sciences Publication Activity Database

    Běhounek, Libor; Bodenhofer, U.; Cintula, Petr; Saminger-Platz, S.

    Linz : Johannes Kepler Universität, 2008 - (Klement, E.; Rodabaugh, S.; Stout, L.). s. 11-14 [Linz Seminar on Fuzzy Set Theory /29./. 12.02.2008-16.02.2008, Linz] R&D Projects: GA AV ČR 1ET100300517; GA AV ČR IAA100300503 Grant ostatní: Program Kontakt / WTZ Czech Republic - Austria Project Project No. 6-07-17/2-2007 Institutional research plan: CEZ:AV0Z10300504 Keywords : t-norm * dominance * fuzzy class theory Subject RIV: BA - General Mathematics

  19. Autozygosity mapping of a large consanguineous Pakistani family reveals a novel non-syndromic autosomal recessive mental retardation locus on 11p15-tel

    DEFF Research Database (Denmark)

    Rehman, Shoaib ur; Baig, Shahid Mahmood; Eiberg, Hans;

    2011-01-01

    Autosomal recessive inherited mental retardation is an extremely heterogeneous disease and accounts for approximately 25% of all non-syndromic mental retardation cases. Autozygosity mapping of a large consanguineous Pakistani family revealed a novel locus for non-syndromic autosomal recessive...... mental retardation (NS-ARMR). The affected individuals showed low IQ and cognitive impairment without any neurological, skeletal, and biochemical abnormalities. All known NS-ARMR genes were excluded by STS markers, so autozygosity mapping by microarray single-nucleotide polymorphism (SNP) analysis were......¿=¿3.31 was calculated for the mapped region. These results suggest a novel genetic locus, MRT17, for NS-ARMR....

  20. Deletion of Indian hedgehog gene causes dominant semi-lethal Creeper trait in chicken.

    Science.gov (United States)

    Jin, Sihua; Zhu, Feng; Wang, Yanyun; Yi, Guoqiang; Li, Junying; Lian, Ling; Zheng, Jiangxia; Xu, Guiyun; Jiao, Rengang; Gong, Yu; Hou, Zhuocheng; Yang, Ning

    2016-01-01

    The Creeper trait, a classical monogenic phenotype of chicken, is controlled by a dominant semi-lethal gene. This trait has been widely cited in the genetics and molecular biology textbooks for illustrating autosomal dominant semi-lethal inheritance over decades. However, the genetic basis of the Creeper trait remains unknown. Here we have utilized ultra-deep sequencing and extensive analysis for targeting causative mutation controlling the Creeper trait. Our results indicated that the deletion of Indian hedgehog (IHH) gene was only found in the whole-genome sequencing data of lethal embryos and Creeper chickens. Large scale segregation analysis demonstrated that the deletion of IHH was fully linked with early embryonic death and the Creeper trait. Expression analysis showed a much lower expression of IHH in Creeper than wild-type chickens. We therefore suggest the deletion of IHH to be the causative mutation for the Creeper trait in chicken. Our findings unravel the genetic basis of the longstanding Creeper phenotype mystery in chicken as the same gene also underlies bone dysplasia in human and mouse, and thus highlight the significance of IHH in animal development and human haploinsufficiency disorders. PMID:27439785

  1. Autosomal recessive diseases among Palestinian Arabs.

    OpenAIRE

    Zlotogora, J

    1997-01-01

    As a consequence of the high consanguinity rate among the Palestinian Arabs, many recessive disorders are present with a relatively high frequency. In a survey of 2000 different Palestinian Arab families who visited our genetic clinic, in 601 an autosomal recessive disease was diagnosed or strongly suspected. The distribution of these disorders was not uniform and some disorders, such as Krabbe disease, were found at high frequency in only a small part of the population. For some other disord...

  2. Inheritance Legal System in Indonesia: A Legal Justice for People

    OpenAIRE

    Yeni Salma Barlinti

    2013-01-01

    As one of Asian countries, Indonesia has varied of cultures and religions. This variety affects positive laws in Indonesia, one of them is inheritance law. Indonesia has three inheritance legal systems, that is, adat inheritance law, Islamic inheritance law, and western inheritance law. Adat inheritance law is a norm of local adat community about inheritance. Islamic inheritance law is a norm of inheritance based on al Qur’an (Islamic holy book) and hadis (words, acts, and silence of Prophet ...

  3. Associations between STR autosomal markers and longevity.

    Science.gov (United States)

    Bediaga, N G; Aznar, J M; Elcoroaristizabal, X; Albóniga, O; Gómez-Busto, F; Artaza Artabe, I; Rocandio, Ana; de Pancorbo, M M

    2015-10-01

    Life span is a complex and multifactorial trait, which is shaped by genetic, epigenetic, environmental, and stochastic factors. The possibility that highly hypervariable short tandem repeats (STRs) associated with longevity has been largely explored by comparing the genotypic pools of long lived and younger individuals, but results so far have been contradictory. In view of these contradictory findings, the present study aims to investigate whether HUMTHO1 and HUMCSF1PO STRs, previously associated with longevity, exert a role as a modulator of life expectancy, as well as to assess the extent to which other autosomal STR markers are associated with human longevity in population from northern Spain. To that end, 21 autosomal microsatellite markers have been studied in 304 nonagenarian individuals (more than 90 years old) and 516 younger controls of European descent. Our results do not confirm the association found in previous studies between longevity and THO1 and CSF1PO loci. However, significant association between longevity and autosomal STR markers D12S391, D22S1045, and DS441 was observed. Even more, when we compared allelic frequency distribution of the 21 STR markers between cases and controls, we found that 6 out of the 21 STRs studied showed different allelic frequencies, thus suggesting that the genomic portrait of the human longevity is far complex and probably shaped by a high number of genomic loci. PMID:26335621

  4. [Inherited amino acid transport disorders].

    Science.gov (United States)

    Igarashi, Y; Tada, K

    1992-07-01

    Disorders due to inherited amino acids transport defect are reviewed. The disorders were categorized into three types of transport defects, namely, brush-border membrane of epithelial cells of small intestine and kidney tubules (Hartnup disease, blue diaper syndrome, cystinuria, iminoglycinuria and lysine malabsorption syndrome), basolateral membrane (lysinuric protein intolerance) and membrane of intracellular organelles (cystinosis and hyperornitinemia-hyperammonemia-homocitrullinuria syndrome). Pathogenesis, clinical feature, laboratory findings, diagnosis, genetics and treatment of these disorders are described, briefly. There is not much data for the transport systems themselves, so that further investigation in molecular and gene levels for transport systems is necessary to clarify the characteristics of the transport and heterogeneity of phenotypes in inherited amino acids transport disorders. PMID:1404888

  5. Symmetry inheritance of scalar fields

    Science.gov (United States)

    Smolić, Ivica

    2015-07-01

    Matter fields do not necessarily have to share the symmetries with the spacetime they live in. When this happens, we speak of the symmetry inheritance of fields. In this paper we classify the obstructions of symmetry inheritance by the scalar fields, both real and complex, and look more closely at the special cases of stationary and axially symmetric spacetimes. Since the symmetry noninheritance is present in the scalar fields of boson stars and may enable the existence of the black hole scalar hair, our results narrow the possible classes of such solutions. Finally, we define and analyse the symmetry noninheritance contributions to the Komar mass and angular momentum of the black hole scalar hair.

  6. Symmetry inheritance of scalar fields

    CERN Document Server

    Smolić, Ivica

    2015-01-01

    Matter fields don't necessarily have to share the symmetries with the spacetime they live in. When this happens, we speak of the symmetry inheritance of fields. In this paper we classify the obstructions of symmetry inheritance by the scalar fields, both real and complex, and look more closely at the special cases of stationary and axially symmetric spacetimes. Since the symmetry noninheritance is present in the scalar fields of boson stars and may enable the existence of the black hole scalar hair, our results narrow the possible classes of such solutions. Finally, we define and analyse the symmetry noninheritance contributions to Komar mass and angular momentum of the black hole scalar hair.

  7. Inheriting geodesic flows

    Indian Academy of Sciences (India)

    D B Lortan; S D Maharaj; N K Dadhich

    2001-06-01

    We investigate the propagation equations for the expansion, vorticity and shear for perfect fluid space-times which are geodesic. It is assumed that space-time admits a conformal Killing vector which is inheriting so that fluid flow lines are mapped conformally. Simple constraints on the electric and magnetic parts of the Weyl tensor are found for conformal symmetry. For homothetic vectors the vorticity and shear are free; they vanish for nonhomothetic vectors. We prove a conjecture for conformal symmetries in the special case of inheriting geodesic flows: there exist no proper conformal Killing vectors ( ≠ 0) for perfect fluids except for Robertson–Walker space-times. For a nonhomothetic vector field the propagation of the quantity ln () along the integral curves of the symmetry vector is homogeneous.

  8. Additivity dominance

    Directory of Open Access Journals (Sweden)

    Paul Rozin

    2009-10-01

    Full Text Available Judgments of naturalness of foods tend to be more influenced by the process history of a food, rather than its actual constituents. Two types of processing of a ``natural'' food are to add something or to remove something. We report in this study, based on a large random sample of individuals from six countries (France, Germany, Italy, Switzerland, UK and USA that additives are considered defining features of what makes a food not natural, whereas ``subtractives'' are almost never mentioned. In support of this, skim milk (with major subtraction of fat is rated as more natural than whole milk with a small amount of natural vitamin D added. It is also noted that ``additives'' is a common word, with a synonym reported by a native speaker in 17 of 18 languages, whereas ``subtractive'' is lexicalized in only 1 of the 18 languages. We consider reasons for additivity dominance, relating it to omission bias, feature positive bias, and notions of purity.

  9. Overview of Inherited Zinc Deficiency in Infants and Children.

    Science.gov (United States)

    Kambe, Taiho; Fukue, Kazuhisa; Ishida, Riko; Miyazaki, Shiho

    2015-01-01

    Zinc nutrition is of special practical importance in infants and children. Poor zinc absorption causes zinc deficiency, which leads to a broad range of consequences such as alopecia, diarrhea, skin lesions, taste disorders, loss of appetite, impaired immune function and neuropsychiatric changes and growth retardation, thus potentially threatening life in infants and children. In addition to dietary zinc deficiency, inherited zinc deficiency, which rarely occurs, is found during the infant stage and early childhood. Recent molecular genetic studies have identified responsible genes for two inherited zinc deficiency disorders, acrodermatitis enteropathica (AE) and transient neonatal zinc deficiency (TNZD), clarifying the pathological mechanisms. Both of these zinc deficiencies are caused by mutations of zinc transporters, although the mechanisms are completely different. AE is an autosomal recessive disorder caused by mutations of the ZIP4 gene, consequently resulting in defective absorption of zinc in the small intestine. In contrast, TNZD is a disorder caused by mutations of the ZnT2 gene, which results in low zinc breast milk in the mother, consequently causing zinc deficiency in the breast-fed infant. In both cases, zinc deficiency symptoms are ameliorated by a daily oral zinc supplementation for the patients. Zinc is definitely one of the key factors for the healthy growth of infants and children, and thus zinc nutrition should receive much attention. PMID:26598882

  10. Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity.

    Science.gov (United States)

    Torres, Juan Manuel; Martinez-Barricarte, Rubén; García-Gómez, Sonia; Mazariegos, Marina S; Itan, Yuval; Boisson, Bertrand; Rholvarez, Rita; Jiménez-Reinoso, Anaïs; del Pino, Lucia; Rodríguez-Pena, Rebeca; Ferreira, Antonio; Hernández-Jiménez, Enrique; Toledano, Victor; Cubillos-Zapata, Carolina; Díaz-Almirón, Mariana; López-Collazo, Eduardo; Unzueta-Roch, José L; Sánchez-Ramón, Silvia; Regueiro, Jose R; López-Granados, Eduardo; Casanova, Jean-Laurent; Pérez de Diego, Rebeca

    2014-12-01

    Heterotrimers composed of B cell CLL/lymphoma 10 (BCL10), mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), and caspase recruitment domain-containing (CARD) family adaptors play a role in NF-κB activation and have been shown to be involved in both the innate and the adaptive arms of immunity in murine models. Moreover, individuals with inherited defects of MALT1, CARD9, and CARD11 present with immunological and clinical phenotypes. Here, we characterized a case of autosomal-recessive, complete BCL10 deficiency in a child with a broad immunodeficiency, including defects of both hematopoietic and nonhematopoietic immunity. The patient died at 3 years of age and was homozygous for a loss-of-expression, loss-of-function BCL10 mutation. The effect of BCL10 deficiency was dependent on the signaling pathway, and, for some pathways, the cell type affected. Despite the noted similarities to BCL10 deficiency in mice, including a deficient adaptive immune response, human BCL10 deficiency in this patient resulted in a number of specific features within cell populations. Treatment of the patient's myeloid cells with a variety of pathogen-associated molecular pattern molecules (PAMPs) elicited a normal response; however, NF-κB-mediated fibroblast functions were dramatically impaired. The results of this study indicate that inherited BCL10 deficiency should be considered in patients with combined immunodeficiency with B cell, T cell, and fibroblast defects. PMID:25365219

  11. Mode of inheritance in psoriasis

    OpenAIRE

    Kumar Arvind; Mohan Lalit; Singh K.; Pandey O; Mukhija R

    1992-01-01

    One hundred and eighty patients of psoriasis and 100 controls were analysed to find out the genetic nature of psoriasis and if so, then to determine the possible mode of inheritance. The prevalence of psoriasis in relatives, percentage of positive family history and percentage of total affected relatives in the patient group was significantly higher than the controls, and clustering of affected relatives in patient group suggested genetic involvement. Ratio of affected and unaffected in the s...

  12. Inherited Disorders of Bilirubin Clearance

    OpenAIRE

    Memon, Naureen; Weinberger, Barry I; Hegyi, Thomas; Aleksunes, Lauren M

    2015-01-01

    Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective 1) unconjugated bilirubin uptake and intrahepatic storage, 2) conjugation of glucuronic acid to bilirubin (e.g. Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), 3) bilirubin excretion into bile (Dubin-Johnson syndrome), or 4) conjugated bilirubin re-uptake (Rotor syndrom...

  13. Light and inherited retinal degeneration

    OpenAIRE

    Paskowitz, D M; LaVail, M.M.; Duncan, J. L.

    2006-01-01

    Light deprivation has long been considered a potential treatment for patients with inherited retinal degenerative diseases, but no therapeutic benefit has been demonstrated to date. In the few clinical studies that have addressed this issue, the underlying mutations were unknown. Our rapidly expanding knowledge of the genes and mechanisms involved in retinal degeneration have made it possible to reconsider the potential value of light restriction in specific genetic contexts. This review summ...

  14. Inherited Control and Firm Performance

    OpenAIRE

    Francisco Pérez-González

    2006-01-01

    I use data from chief executive officer (CEO) successions to examine the impact of inherited control on firms? performance. I find that firms where incoming CEOs are related to the departing CEO, to a founder, or to a large shareholder by either blood or marriage underperform in terms of operating profitability and market-to-book ratios, relative to firms that promote unrelated CEOs. Consistent with wasteful nepotism, lower performance is prominent in firms that appoint family CEOs who did no...

  15. Distribution of lod scores under uncertain mode of inheritance.

    OpenAIRE

    MacLean, C J; Bishop, D T; Sherman, S L; Diehl, S. R.

    1993-01-01

    We consider probability distributions of alternative lod statistics, differing in their treatment of segregation parameters when mode of inheritance is uncertain. A particular pedigree structure and a dominant genetic system displaying incomplete penetrance are analyzed. Lod scores calculated assuming an incorrect segregation model appear to conform quite well to the chi 2 distribution in the absence of linkage. In the presence of linkage, some power is lost. However, if lod scores are calcul...

  16. The β1-subunit of Na(v1.5 cardiac sodium channel is required for a dominant negative effect through α-α interaction.

    Directory of Open Access Journals (Sweden)

    Aurélie Mercier

    Full Text Available Brugada syndrome (BrS is an inherited autosomal dominant cardiac channelopathy. Several mutations on the cardiac sodium channel Na(v1.5 which are responsible for BrS lead to misfolded proteins that do not traffic properly to the plasma membrane. In order to mimic patient heterozygosity, a trafficking defective mutant, R1432G was co-expressed with Wild Type (WT Na(v1.5 channels in HEK293T cells. This mutant significantly decreased the membrane Na current density when it was co-transfected with the WT channel. This dominant negative effect did not result in altered biophysical properties of Na(v1.5 channels. Luminometric experiments revealed that the expression of mutant proteins induced a significant reduction in membrane expression of WT channels. Interestingly, we have found that the auxiliary Na channel β(1-subunit was essential for this dominant negative effect. Indeed, the absence of the β(1-subunit prevented the decrease in WT sodium current density and surface proteins associated with the dominant negative effect. Co-immunoprecipitation experiments demonstrated a physical interaction between Na channel α-subunits. This interaction occurred only when the β(1-subunit was present. Our findings reveal a new role for β(1-subunits in cardiac voltage-gated sodium channels by promoting α-α subunit interaction which can lead to a dominant negative effect when one of the α-subunits shows a trafficking defective mutation.

  17. COL11A2 mutation associated with autosomal recessive Weissenbacher-Zweymuller syndrome: molecular and clinical overlap with otospondylomegaepiphyseal dysplasia (OSMED).

    Science.gov (United States)

    Harel, Tamar; Rabinowitz, Ronen; Hendler, Netta; Galil, Aharon; Flusser, Hagit; Chemke, Juan; Gradstein, Libe; Lifshitz, Tova; Ofir, Rivka; Elbedour, Khalil; Birk, Ohad S

    2005-01-01

    Autosomal recessive Weissenbacher-Zweymuller syndrome (WZS) is a skeletal dysplasia characterized by rhizomelic dwarfism and severe hearing loss. Mutations in the COL11A2 gene have been implicated in causing the autosomal dominant form of this syndrome as well as non-ocular Stickler syndrome and the autosomal recessive syndrome otospondylomegaepiphyseal dysplasia (OSMED). In a consanguineous Bedouin tribe living in Southern Israel, five individuals affected by autosomal recessive WZS were available for genetic analysis. Homozygosity of a mutation in the COL11A2 gene was found in all affected individuals. This finding lends molecular support to the clinical notion that autosomal recessive WZS and OSMED are a single entity. PMID:15558753

  18. Plate tectonics, damage and inheritance.

    Science.gov (United States)

    Bercovici, David; Ricard, Yanick

    2014-04-24

    The initiation of plate tectonics on Earth is a critical event in our planet's history. The time lag between the first proto-subduction (about 4 billion years ago) and global tectonics (approximately 3 billion years ago) suggests that plates and plate boundaries became widespread over a period of 1 billion years. The reason for this time lag is unknown but fundamental to understanding the origin of plate tectonics. Here we suggest that when sufficient lithospheric damage (which promotes shear localization and long-lived weak zones) combines with transient mantle flow and migrating proto-subduction, it leads to the accumulation of weak plate boundaries and eventually to fully formed tectonic plates driven by subduction alone. We simulate this process using a grain evolution and damage mechanism with a composite rheology (which is compatible with field and laboratory observations of polycrystalline rocks), coupled to an idealized model of pressure-driven lithospheric flow in which a low-pressure zone is equivalent to the suction of convective downwellings. In the simplest case, for Earth-like conditions, a few successive rotations of the driving pressure field yield relic damaged weak zones that are inherited by the lithospheric flow to form a nearly perfect plate, with passive spreading and strike-slip margins that persist and localize further, even though flow is driven only by subduction. But for hotter surface conditions, such as those on Venus, accumulation and inheritance of damage is negligible; hence only subduction zones survive and plate tectonics does not spread, which corresponds to observations. After plates have developed, continued changes in driving forces, combined with inherited damage and weak zones, promote increased tectonic complexity, such as oblique subduction, strike-slip boundaries that are subparallel to plate motion, and spalling of minor plates. PMID:24717430

  19. Inherited Disorders of Bilirubin Clearance

    Science.gov (United States)

    Memon, Naureen; Weinberger, Barry I; Hegyi, Thomas; Aleksunes, Lauren M

    2016-01-01

    Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective 1) unconjugated bilirubin uptake and intrahepatic storage, 2) conjugation of glucuronic acid to bilirubin (e.g. Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), 3) bilirubin excretion into bile (Dubin-Johnson syndrome), or 4) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy. PMID:26595536

  20. ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Montecchiani, Celeste; Pedace, Lucia; Lo Giudice, Temistocle; Casella, Antonella; Mearini, Marzia; Gaudiello, Fabrizio; Pedroso, José L; Terracciano, Chiara; Caltagirone, Carlo; Massa, Roberto; St George-Hyslop, Peter H; Barsottini, Orlando G P; Kawarai, Toshitaka; Orlacchio, Antonio

    2016-01-01

    Charcot-Marie-Tooth disease is a group of hereditary peripheral neuropathies that share clinical characteristics of progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, as well as diminished tendon reflexes. Hundreds of causative DNA changes have been found, but much of the genetic basis of the disease is still unexplained. Mutations in the ALS5/SPG11/KIAA1840 gene are a frequent cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and peripheral axonal neuropathy, and account for ∼ 40% of autosomal recessive juvenile amyotrophic lateral sclerosis. The overlap of axonal Charcot-Marie-Tooth disease with both diseases, as well as the common autosomal recessive inheritance pattern of thin corpus callosum and axonal Charcot-Marie-Tooth disease in three related patients, prompted us to analyse the ALS5/SPG11/KIAA1840 gene in affected individuals with autosomal recessive axonal Charcot-Marie-Tooth disease. We investigated 28 unrelated families with autosomal recessive axonal Charcot-Marie-Tooth disease defined by clinical, electrophysiological, as well as pathological evaluation. Besides, we screened for all the known genes related to axonal autosomal recessive Charcot-Marie-Tooth disease (CMT2A2/HMSN2A2/MFN2, CMT2B1/LMNA, CMT2B2/MED25, CMT2B5/NEFL, ARCMT2F/dHMN2B/HSPB1, CMT2K/GDAP1, CMT2P/LRSAM1, CMT2R/TRIM2, CMT2S/IGHMBP2, CMT2T/HSJ1, CMTRID/COX6A1, ARAN-NM/HINT and GAN/GAN), for the genes related to autosomal recessive hereditary spastic paraplegia with thin corpus callosum and axonal peripheral neuropathy (SPG7/PGN, SPG15/ZFYVE26, SPG21/ACP33, SPG35/FA2H, SPG46/GBA2, SPG55/C12orf65 and SPG56/CYP2U1), as well as for the causative gene of peripheral neuropathy with or without agenesis of the corpus callosum (SLC12A6). Mitochondrial disorders related to Charcot-Marie-Tooth disease type 2 were also excluded by sequencing POLG and TYMP genes. An additional locus for autosomal recessive Charcot

  1. Inheritance of resistance to anthracnose stalk rot (Colletotrichum graminicola) in tropical maize inbred lines

    OpenAIRE

    Herberte Pereira da Silva; Regina Mélo Sartori Coêlho Morello; Maria Teresa Gomes Lopes; Kátia Regiane Brunelli; Rodrigo Rodrigues Matiello; Luis Eduardo Aranha Camargo

    2012-01-01

    Generation means was used to study the mode of inheritance of resistance to anthracnose stalk rot in tropical maize. Each population was comprised of six generations in two trials under a randomized block design. Inoculations were performed using a suspension of 10*5 conidia mL -1 applied into the stalk. Internal lesion length was directly measured by opening the stalk thirty days after inoculation. Results indicated contrasting modes of inheritance. In one population, dominant gene effects p...

  2. Inheritance Pattern of Temephos Resistance, an Organophosphate Insecticide, in Aedes aegypti (L.)

    OpenAIRE

    Vinaya Shetty; Deepak Sanil; Shetty, N. J.

    2015-01-01

    The present paper reports the mode of inheritance of resistance in laboratory induced temephos resistant and susceptible strains of Ae. aegypti. Homozygous resistant and susceptible strains of Ae. aegypti were generated by selective inbreeding at a diagnostic dose of 0.02 mg/L of temephos. Genetic crosses were carried out between these strains to determine the inheritance pattern of temephos resistance. The log-dosage probit mortality relationships and degree of dominance (D) ...

  3. Paternal inheritance of mitochondria in Chlamydomonas.

    Science.gov (United States)

    Nakamura, Soichi

    2010-03-01

    To analyze mitochondrial DNA (mtDNA)inheritance, differences in mtDNA between Chlamydomonas reinhardtii and Chlamydomonas smithii, respiration deficiency and antibiotic resistance were used to distinguish mtDNA origins. The analyses indicated paternal inheritance. However, these experiments raised questions regarding whether paternal inheritance occurred normally.Mitochondrial nucleoids were observed in living zygotes from mating until 3 days after mating and then until progeny formation. However, selective disappearance of nucleoids was not observed. Subsequently, experimental serial backcrosses between the two strains demonstrated strict paternal inheritance. The fate of mt+ and mt- mtDNA was followed using the differences in mtDNA between the two strains. The slow elimination of mt+ mtDNA through zygote maturation in darkness was observed, and later the disappearance of mt+ mtDNA was observed at the beginning of meiosis. To explain the different fates of mtDNA, methylation status was investigated; however, no methylation was detected. Variously constructed diploid cells showed biparental inheritance. Thus, when the mating process occurs normally, paternal inheritance occurs. Mutations disrupting mtDNA inheritance have not yet been isolated. Mutations that disrupt maternal inheritance of chloroplast DNA (cpDNA) do not disrupt inheritance of mtDNA. The genes responsible for mtDNA inheritance are different from those of chloroplasts. PMID:20069335

  4. Atypical mitochondrial inheritance patterns in eukaryotes.

    Science.gov (United States)

    Breton, Sophie; Stewart, Donald T

    2015-10-01

    Mitochondrial DNA (mtDNA) is predominantly maternally inherited in eukaryotes. Diverse molecular mechanisms underlying the phenomenon of strict maternal inheritance (SMI) of mtDNA have been described, but the evolutionary forces responsible for its predominance in eukaryotes remain to be elucidated. Exceptions to SMI have been reported in diverse eukaryotic taxa, leading to the prediction that several distinct molecular mechanisms controlling mtDNA transmission are present among the eukaryotes. We propose that these mechanisms will be better understood by studying the deviations from the predominating pattern of SMI. This minireview summarizes studies on eukaryote species with unusual or rare mitochondrial inheritance patterns, i.e., other than the predominant SMI pattern, such as maternal inheritance of stable heteroplasmy, paternal leakage of mtDNA, biparental and strictly paternal inheritance, and doubly uniparental inheritance of mtDNA. The potential genes and mechanisms involved in controlling mitochondrial inheritance in these organisms are discussed. The linkage between mitochondrial inheritance and sex determination is also discussed, given that the atypical systems of mtDNA inheritance examined in this minireview are frequently found in organisms with uncommon sexual systems such as gynodioecy, monoecy, or andromonoecy. The potential of deviations from SMI for facilitating a better understanding of a number of fundamental questions in biology, such as the evolution of mtDNA inheritance, the coevolution of nuclear and mitochondrial genomes, and, perhaps, the role of mitochondria in sex determination, is considerable. PMID:26501689

  5. Disease: H00720 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available y an autosomal-dominant inheritance without familial deafness. The Jervell and Lange-Nielsen syndrome (JLNS)... has an autosomal-recessive pattern of inheritance and is associated with deafness. Cardiovascular disease (

  6. Mutations in c10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism

    DEFF Research Database (Denmark)

    Grønskov, Karen; Dooley, Christopher M; Østergaard, Elsebet;

    2013-01-01

    Autosomal-recessive albinism is a hypopigmentation disorder with a broad phenotypic range. A substantial fraction of individuals with albinism remain genetically unresolved, and it has been hypothesized that more genes are to be identified. By using homozygosity mapping of an inbred Faroese family......, we identified a 3.5 Mb homozygous region (10q22.2-q22.3) on chromosome 10. The region contains five protein-coding genes, and sequencing of one of these, C10orf11, revealed a nonsense mutation that segregated with the disease and showed a recessive inheritance pattern. Investigation of additional...... individual originating from Lithuania. Immunohistochemistry showed localization of C10orf11 in melanoblasts and melanocytes in human fetal tissue, but no localization was seen in retinal pigment epithelial cells. Knockdown of the zebrafish (Danio rerio) homolog with the use of morpholinos resulted in...

  7. A Linkage Study in 8 Pakistani Families Segregating as Autosomal Recessive Primary Microcephaly

    Directory of Open Access Journals (Sweden)

    M. Hassanullah

    2011-07-01

    Full Text Available The current study was designed to find the most frequent MCPH phenotype in inbred Pakistani families. Primary microcephaly is marked by small brain size and is usually inherited as recessive trait. In the present study, we performed linkage analysis on 8 Pakistani families with autosomal recessive primary microcephaly (MCPH and linked 6 of them to known MCPH genes/loci like MCPH1 (Microcephalin, MCPH3 (CDK5RAP2 and MCPH5 (ASPM. Majority of the families showed linkage with MCPH5, the most common MCPH locus in Pakistan. The linked families were then subjected to mutational analysis, revealing a previously known G to A transition at nucleotide position 3978 in exon 17 of ASPM gene in three of the families. To decrease its incidence, it is indispensible to train the people of the possible devastating outcome of cousin marriages and to find the carriers through carrier screening programs.

  8. Inheritance of resistance to anthracnose stalk rot (Colletotrichum graminicola in tropical maize inbred lines

    Directory of Open Access Journals (Sweden)

    Herberte Pereira da Silva

    2012-09-01

    Full Text Available Generation means was used to study the mode of inheritance of resistance to anthracnose stalk rot in tropical maize. Each population was comprised of six generations in two trials under a randomized block design. Inoculations were performed using a suspension of 10*5 conidia mL -1 applied into the stalk. Internal lesion length was directly measured by opening the stalk thirty days after inoculation. Results indicated contrasting modes of inheritance. In one population, dominant gene effects predominated. Besides, additive x dominant and additive x additive interactions were also found. Intermediate values of heritability indicated a complex resistance inheritance probably conditioned by several genes of small effects. An additive-dominant genetic model sufficed to explain the variation in the second population, where additive gene effects predominated. Few genes of major effects control disease resistance in this cross. Heterosis widely differed between populations, which can be attributed to the genetic background of the parental resistant lines.

  9. Calcium Ions in Inherited Cardiomyopathies.

    Science.gov (United States)

    Deftereos, Spyridon; Papoutsidakis, Nikolaos; Giannopoulos, Georgios; Angelidis, Christos; Raisakis, Konstantinos; Bouras, Georgios; Davlouros, Periklis; Panagopoulou, Vasiliki; Goudevenos, John; Cleman, Michael W; Lekakis, John

    2016-01-01

    Inherited cardiomyopathies are a known cause of heart failure, although the pathways and mechanisms leading from mutation to the heart failure phenotype have not been elucidated. There is strong evidence that this transition is mediated, at least in part, by abnormal intracellular Ca(2+) handling, a key ion in ventricular excitation, contraction and relaxation. Studies in human myocytes, animal models and in vitro reconstituted contractile protein complexes have shown consistent correlations between Ca(2+) sensitivity and cardiomyopathy phenotype, irrespective of the causal mutation. In this review we present the available data about the connection between mutations linked to familial hypertrophic (HCM), dilated (DCM) and restrictive (RCM) cardiomyopathy, right ventricular arrhythmogenic cardiomyopathy/dysplasia (ARVC/D) as well as left ventricular non-compaction and the increase or decrease in Ca(2+) sensitivity, together with the results of attempts to reverse the manifestation of heart failure by manipulating Ca(2+) homeostasis. PMID:26411603

  10. Domination, Eternal Domination, and Clique Covering

    Directory of Open Access Journals (Sweden)

    Klostermeyer William F.

    2015-05-01

    Full Text Available Eternal and m-eternal domination are concerned with using mobile guards to protect a graph against infinite sequences of attacks at vertices. Eternal domination allows one guard to move per attack, whereas more than one guard may move per attack in the m-eternal domination model. Inequality chains consisting of the domination, eternal domination, m-eternal domination, independence, and clique covering numbers of graph are explored in this paper.

  11. On identification problems requiring linked autosomal markers.

    Science.gov (United States)

    Egeland, Thore; Sheehan, Nuala

    2008-06-01

    This paper considers identification problems based on DNA marker data. The topics we discuss are general, but we will exemplify them in a simple context. There is DNA available from two persons. There is uncertainty about the relationship between the two individuals and a number of hypotheses describing the possible relationship is available. The task is to determine the most likely pedigree. This problem is fairly standard. However, there are some problems that cannot be solved using DNA from independently segregating loci. For example, the likelihoods for (i) grandparent-grandchild, (ii) uncle-niece and (iii) half-sibs coincide for such DNA data and so these relations cannot be distinguished on the basis of markers normally used for forensic identification problems: the likelihood ratio comparing any pair of hypotheses will be unity. Sometimes, but not in the examples we consider, other sources of DNA like mtDNA or sex chromosomes can help to distinguish between such equally likely possibilities. Prior information can likewise be of use. For instance, age information can exclude alternative (i) above and also indicate that alternative (iii) is apriori more likely than alternative (ii). More generally, the above problems can be solved using linked autosomal markers. To study the problem in detail and understand how linkage works in this regard, we derive an explicit formula for a pair of linked markers. The formula extends to independent pairs of linked markers. While this approach adds to the understanding of the problem, more markers are required to obtain satisfactory results and then the Lander-Green algorithm is needed. Simulation experiments are presented based on a range of scenarios and we conclude that useful results can be obtained using available freeware (MERLIN and R). The main message of this paper is that linked autosomal markers deserve greater attention in forensic genetics and that the required laboratory and statistical analyses can be performed

  12. Autosomal Recessive Congenital Ichthyosis in American Bulldogs Is Associated With NIPAL4 (ICHTHYIN) Deficiency.

    Science.gov (United States)

    Mauldin, E A; Wang, P; Evans, E; Cantner, C A; Ferracone, J D; Credille, K M; Casal, M L

    2015-07-01

    A minority of patients with nonsyndromic autosomal recessive congenital ichthyosis (ARCI) display mutations in NIPAL4 (ICHTHYIN). This protein plays a role in epidermal lipid metabolism, although the mechanism is unknown. The study describes a moderate form of ARCI in an extended pedigree of American Bulldogs that is linked to the gene encoding ichthyin. The gross phenotype was manifest as a disheveled pelage shortly after birth, generalized scaling, and adherent brown scale with erythema of the abdominal skin. Pedigree analysis indicated an autosomal recessive mode of inheritance. Ultrastructurally, the epidermis showed discontinuous lipid bilayers, unprocessed lipid within corneocytes, and abnormal lamellar bodies. Linkage analysis, performed by choosing simple sequence repeat markers and single-nucleotide polymorphisms near genes known to cause ACRI, revealed an association with NIPAL4. NIPAL4 was identified and sequenced using standard methods. No mutation was identified within the gene, but affected dogs had a SINE element 5' upstream of exon 1 in a highly conserved region. Of 545 DNA samples from American Bulldogs, 32 dogs (17 females, 15 males) were homozygous for the polymerase chain reaction fragment. All affected dogs were homozygous, with parents heterozygous for the insertion. Immunolabeling revealed an absence of ichthyin in the epidermis. This is the first description of ARCI associated with decreased expression of NIPAL4 in nonhuman species. PMID:25322746

  13. Inherited Bone Marrow Failure Syndromes (IBMFS)

    Science.gov (United States)

    The NCI IBMFS Cohort Study consists of affected individuals and their immediate families in North America who have an inherited bone marrow failure syndrome (IBMFS)-either one that has been specifically identified and defined, or bone marrow failure that appears to be inherited but has not yet been clearly identified as having a genetic basis.

  14. Inheritance of Evolved Glyphosate Resistance in a North Carolina Palmer Amaranth (Amaranthus palmeri Biotype

    Directory of Open Access Journals (Sweden)

    Aman Chandi

    2012-01-01

    Full Text Available Inheritance of glyphosate resistance in a Palmer amaranth biotype from North Carolina was studied. Glyphosate rates for 50% survival of glyphosate-resistant (GR and glyphosate-susceptible (GS biotypes were 1288 and 58 g ha−1, respectively. These values for F1 progenies obtained from reciprocal crosses (GR×GS and GS×GR were 794 and 501 g ha−1, respectively. Dose response of F1 progenies indicated that resistance was not fully dominant over susceptibility. Lack of significant differences between dose responses for reciprocal F1 families suggested that genetic control of glyphosate resistance was governed by nuclear genome. Analysis of F1 backcross (BC1F1 families showed that 10 and 8 BC1F1 families out of 15 fitted monogenic inheritance at 2000 and 3000 g ha−1 glyphosate, respectively. These results indicate that inheritance of glyphosate resistance in this biotype is incompletely dominant, nuclear inherited, and might not be consistent with a single gene mechanism of inheritance. Relative 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS copy number varied from 22 to 63 across 10 individuals from resistant biotype. This suggested that variable EPSPS copy number in the parents might be influential in determining if inheritance of glyphosate resistance is monogenic or polygenic in this biotype.

  15. Macular sensitivity and fixation patterns in patients with autosomal dominant optic atrophy

    DEFF Research Database (Denmark)

    Rönnbäck, Cecilia; Larsen, Michael

    2014-01-01

    in the nasal macula (13.6 (± 5.7) dB versus 19.7 (± 0.7) dB) and in the central macula (14.2 (± 5.1) dB versus 19.9 (± 0.3) dB). The average sensitivity decreased with decreasing BCVA in ADOA (p < 0.0001). Stable fixation was found in 58% of ADOA patients versus 86% of controls, and relatively...... unstable fixation was observed in 35% of ADOA patients versus 14% of controls. Unstable fixation was found only in ADOA, where its prevalence was 7%. CONCLUSION: ADOA was associated with unstable fixation and subnormal microperimetric sensitivity, especially in the central and nasal macula where the...

  16. Mutation Identification in A 5-Generation Pedigree with Autosomal Dominant Retinitis Pigmentosa

    Institute of Scientific and Technical Information of China (English)

    滕云; 田虹; 王慧; 胡晓峰; 王嵬; 陈燕; 杨真荣

    2003-01-01

    An extended 5-generation family has been investigated in which 32 of the 111 familymembers were diagnosed as having retinitis pigmentosa (RP). The proband was a 58-year old malein whom night-blindness was first observed in early childhood, with almost loss of vision by 52years of age. The symptoms observed in other family members included night-blindness, impairedvision and visual field loss. Dementia, digital abnormalities, deaf-mutism and mental retardationwere variously diagnosed in a number of individuals with RP. The affected and unaffected familymembers were tested for mutations in a range of candidate genes. The 8 exons of three candidategenes have been analyzed by polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP) and DNA sequencing techniques. A novel mutation was identified in the rhodopsingene at codon 52 of exon 1 (TTC-TAC) that resulted in a substitution of Phe to Tyr.

  17. Morphologic,mechanical and functional sonographic parameters of arteries in autosomal dominant polycystic kidney disease

    Institute of Scientific and Technical Information of China (English)

    戎殳

    2006-01-01

    Objective To investigate whether the risk factors of cardiovascular disease exist in early stage of ADPKD patients with normal renal function. Methods Morphologic , mechanical and functional sonographic parameters of arteries were examined by high-frequency ultrasonography in 32 hypertensive and 28 normotensive ADPKD patients with preserved renal function, 25 patients with es-

  18. Novel autosomal dominant mandibulofacial dysostosis with ptosis: clinical description and exclusion of TCOF1

    OpenAIRE

    Hedera, P; Toriello, H; Petty, E

    2002-01-01

    Methods: Six affected family members underwent a complete medical genetics physical examination and two affected subjects had skeletal survey. All available medical records were reviewed. Linkage analysis using the markers spanning the TCOF1 locus was performed. One typically affected family member had a high resolution karyotype.

  19. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL in Argentina

    Directory of Open Access Journals (Sweden)

    Maximiliano A Hawkes

    2015-09-01

    Full Text Available CADASIL is the most common cause of hereditary stroke and vascular dementia. Published information about this disease in South America is scant. We describe clinical and demographic characteristics of 13 patients (10 families with CADASIL from Argentina.Methods Medical records, diagnostic tests and family history of patients with CADASIL were reviewed.Results Thirteen patients with CADASIL (10 families were included. All patients had European ancestry. Initial presentation was stroke in most patients (n = 11. Stroke patients later developed cognitive complaints (n = 9, migraine with aura (n = 1, apathy (n = 4 and depression (n = 6. External capsule and temporal lobe involvement on MRI were characteristic imaging findings. Two patients died after intracerebral hemorrhage.Conclusion This is the first report of non-related patients with CADASIL in South America addressing ancestry. Since European ancestry is not highly prevalent in all South American countries, there may be variable incidence of CADASIL within this region.

  20. Impaired Cleavage of Preproinsulin Signal Peptide Linked to Autosomal-Dominant Diabetes

    OpenAIRE

    Liu, Ming; Lara-Lemus, Roberto; Shan, Shu-ou; Wright, Jordan; Haataja, Leena; Barbetti, Fabrizio; Guo, Huan; Larkin, Dennis; Arvan, Peter

    2012-01-01

    Recently, missense mutations upstream of preproinsulin’s signal peptide (SP) cleavage site were reported to cause mutant INS gene-induced diabetes of youth (MIDY). Our objective was to understand the molecular pathogenesis using metabolic labeling and assays of proinsulin export and insulin and C-peptide production to examine the earliest events of insulin biosynthesis, highlighting molecular mechanisms underlying β-cell failure plus a novel strategy that might ameliorate the MIDY syndrome. W...

  1. The myosin chaperone UNC45B is involved in lens development and autosomal dominant juvenile cataract

    DEFF Research Database (Denmark)

    Hansen, Lars; Comyn, Sophie; Mang, Yuan;

    2014-01-01

    -type embryos resulted in development of a phenotype similar to the steif mutant. The p.Arg805Trp alteration in the mammalian UNC45B gene suggests that developmental cataract may be caused by a defect in non-muscle myosin assembly during maturation of the lens fiber cells.European Journal of Human Genetics...... in myosin assembly. The mutation changes p.Arg805 to Trp in the UCS domain, an amino acid that is highly conserved from yeast to human. UNC45B is strongly expressed in the heart and skeletal muscle tissue, but here we show expression in human embryo eye and zebrafish lens. The zebrafish mutant steif......, carrying an unc45b nonsense mutation, has smaller eyes than wild-type embryos and shows accumulation of nuclei in the lens. Injection of RNA encoding the human wild-type UNC45B protein into the steif homozygous embryo reduced the nuclei accumulation and injection of human mutant UNC45B cDNA in wild...

  2. Asymmetric dimethylarginine and lipid peroxidation products in early autosomal dominant polycystic kidney disease

    DEFF Research Database (Denmark)

    Wang, Dan; Strandgaard, S.; Borresen, M.L.;

    2008-01-01

    nitric oxide synthase and the lipid peroxidation product 13-hydroxyoctadecadienoic acid (HODE) as a marker of oxidative stress in patients with early ADPKD. Study Design: Cross-sectional study. Setting & Participants: Patients with early ADPKD (n = 27) and age-matched volunteers (n = 30) from a single...... academic medical center. Factor: Patients with ADPKD versus controls. Outcomes & Measurement: Plasma (P) levels, urinary (U) excretion, and urinary clearance (C) of ADMA and HODE. Because of multiple comparisons, P for significance is considered less than 0.0167. Results: Patients with ADPKD had......-sectional nature of study, and limited number of markers of oxidative stress. Conclusions: P-ADMA and P-HODE levels are increased in patients with early ADPKD. Increased P-ADMA level is related to decreased CADMA and is accompanied by oxidative stress. Am J Kidney Dis 51:184-191. (c) 2008 by the National Kidney...

  3. Potential Deleterious Effects of Vasopressin in Chronic Kidney Disease and Particularly Autosomal Dominant Polycystic Kidney Disease

    NARCIS (Netherlands)

    Meijer, E.; Boertien, W. E.; Zietse, R.; Gansevoort, R. T.

    2011-01-01

    The antidiuretic hormone vasopressin is crucial for regulating free water clearance in normal physiology. However, it has also been hypothesized that vasopressin has deleterious effects on the kidney. Vasopressin is elevated in animals and patients with chronic kidney disease. Suppression of vasopre

  4. Ultrabiomicroscopic-Histopathologic Correlations in Individuals with Autosomal Dominant Congenital Microcoria: Three-Generation Family Report

    Directory of Open Access Journals (Sweden)

    Arturo Ramirez-Miranda

    2011-05-01

    Full Text Available Background: Congenital microcoria (CMC is due to a maldevelopment of the dilator pupillae muscle of the iris, with a pupil diameter of less than 2 mm. It is associated with juvenile open angle glaucoma and myopia. We report on a three-generation Mexican-Mestizo family with CMC. The eldest member’s iris biopsy proved muscle anomalies. Further, we analyzed novel ultrasound biomicroscopy findings in the family members who did not require surgery. Patients and Methods: A 62-year-old woman, her 41-year-old son and her 9-year-old grandson affected with microcoria since birth, documented by clinical examination and ultrasound biomicroscopy. The eldest member underwent phacoemulsification, and a biopsy of the iris and the anterior capsule of the lens was taken. Results: Ultrasound biomicroscopy confirmed the CMC diagnosis showing iris thinning and a pupil diameter of less than 2 mm. Histopathology of the iris showed a significant reduction of smooth muscle cells, but no alterations of the anterior lens capsule. Discussion: Although CMC is a rare disorder, which is due to a maldevelopment of the dilator pupillae muscle of the iris, it could be associated with juvenile open angle glaucoma and myopia; therefore, precise diagnosis is required. Ultrasound biomicroscopy could be a great option to confirm the disorder.

  5. Autosomal dominant C1149R von Willebrand disease: phenotypic findings and their implications

    OpenAIRE

    Pérez-Rodríguez, Almudena; García-Rivero, Aranzazu; Lourés, Esther; López-Fernández, Maria Fernanda; Rodríguez-Trillo, Angela; Batlle, Javier

    2009-01-01

    The classification and even the diagnosis of von Willebrand disease continues to evolve. In this paper, the authors show how a detailed examination of difficult cases using clinical laboratory and molecular analyses can be used to reach a clinically useful conclusion. See related perspective article on page 610.

  6. Least Privileges and Role's Inheritance of RBAC

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The main advantages of role-based access control (RBAC) are able to support the well-known security principles and roles' inheritance. But for there remains a lack of specific definition and the necessary formalization for RBAC, it is hard to realize RBAC in practical work. Our contribution here is to formalize the main relations of RBAC and take first step to propose concepts of action closure and data closure of a role, based on which we got the specification and algorithm for the least privileges of a role. We propose that roles' inheritance should consist of inheritance of actions and inheritance of data, and then we got the inheritance of privileges among roles, which can also be supported by existing exploit tools.

  7. Inheritance of Ear Tip-Barrenness Trait in Maize

    Institute of Scientific and Technical Information of China (English)

    MENG Zhao-dong; ZHANG Fa-jun; DING Zhao-hua; SUN Qi; WANG Li-ming; GUO Qing-fa; WANG Hong-gang

    2007-01-01

    The aim of this paper is to study the inheritance pattern of ear tip-barrenness trait in maize (Zea mays L.). Ear tipbarrenness trait in maize can be classified into two types, tip-barren and tip-barrenless. Two inbred lines, Ix01-3 (tipbarrenless type), wx04-1 (tip-barren type), and their F1, F2, BC1, BC2 generations were analyzed on their ear tip-barrenness types. Results showed that F1 was tip-barren type; the ratio of tip-barren type versus tip-barrenless type followed a 12.78∶1 ratio in F2 segregation population and a 2.75∶1 ratio in BC1. χ2 test indicated that the trait of ear tip-barrenness type followed an inheritance pattern of 2 duplicate dominant genes. SPSS analysis indicated that the trait of ear tip-barrenness length is of abnormal distribution. Above results mean that: (1) The trait of maize ear tip-barrenness type is controlled by2 duplicate dominant genes; tip-barren type is dominant over tip-barrenless type; (2) the trait of tip-barrenness length is a quantitative character controlled by polygene with major genes expected.

  8. [Inherited thrombopathia in Simmental cattle].

    Science.gov (United States)

    Aebi, M; Wiedemar, N; Drögemüller, C; Zanolari, R

    2016-02-01

    During the years 2012 to 2014, a total of 5 affected Simmental cattle showing persistent bleeding after minor or unknown trauma, were presented at the Clinic for Ruminants or at the Institute for Genetics of the Vetsuisse-Faculty, University of Berne. The homozygous mutation RASGRP2, initially reported in 2007, was present in all these cases and all available parents were heterozygous carriers thus confirming the recessive mode of inheritance. Three affected animals died as a result of persistent bleeding. One animal was stabilized at the Clinic for Ruminants and was slaughtered one month later. Another case showing persistent bleeding and several hematomas was euthanized after genotyping. A frequency of 10% carriers for the associated mutation was detected in a sample of 145 Simmental sires which were used 2013 for artificial insemination in Switzerland. These bulls are designated as TP carriers and should not be used uncontrolled. Breeding organizations in Switzerland make use of the gene test to select bulls which do not carry the mutation. PMID:27145685

  9. Leading the Team You Inherit.

    Science.gov (United States)

    Watkins, Michael D

    2016-06-01

    Most leaders don't have the luxury of building their teams from scratch. Instead they're put in charge of an existing group, and they need guidance on the best way to take over and improve performance. Watkins, an expert on transitions, suggests a three-step approach: Assess. Act quickly to size up the personnel you've inherited, systematically gathering data from one-on-one chats, team meetings, and other sources. Reflect, too, on the business challenges you face, the kinds of people you want in various roles, and the degree to which they need to collaborate. Reshape. Adjust the makeup of the team by moving people to new positions, shifting their responsibilities, or replacing them. Make sure that everyone is aligned on goals and how to achieve them--you may need to change the team's stated direction. Consider also making changes in the way the team operates (reducing the frequency of meetings, for example, or creating new subteams). Then establish ground rules and processes to sustain desired behaviors, and revisit those periodically. Accelerate team development. Set your people up for some early wins. Initial successes will boost everyone's confidence and reinforce the value of your new operating model, thus paving the way for ongoing growth. PMID:27491196

  10. Qualitative inheritance of rind pattern and flesh color in watermelon.

    Science.gov (United States)

    Gusmini, Gabriele; Wehner, Todd C

    2006-01-01

    Watermelon [Citrullus lanatus (Thunb.) Matsum. & Nakai var. lanatus] is a diverse species, with fruits of different sizes, shapes, rind patterns, and flesh colors. This study measured the inheritance of novel rind phenotypes and verified the genetics of white, red, salmon yellow, and canary yellow flesh colors. For each of the 11 crosses, six generations (P(a)S1, P(b)S1, F1, F2, BC1P(a), and BC1P(b)) were produced to form 11 families. Three new genes were identified and designated as follows: Scr for the scarlet red flesh color of Dixielee and Red-N-Sweet, Yb for the yellow belly (ground spot) of Black Diamond Yellow Belly, and ins for the intermittent stripes of Navajo Sweet. The inheritance of the C gene for the canary yellow flesh color was verified as single dominant, and a new inbred type line was developed possessing that gene. Aberrations in the segregation of red, white, and salmon yellow flesh colors were recorded, raising questions on the inheritance of these traits. Finally, the spotted phenotype from Moon and Stars was combined with light green and gray rind patterns for the development of novel cultivars with distinctive rind patterns. PMID:16489140

  11. X linked dominant congenital isolated bilateral ptosis: the definition and characterisation of a new condition

    OpenAIRE

    McMullan, T; Tyers, A

    2001-01-01

    AIMS—To characterise the inheritance of ptosis in one particular pedigree.
METHODS—The pedigree was analysed clinically and genetically to assess the mode of inheritance and to ascribe a gene locus for the condition.
RESULTS—Affected members of the pedigree have bilateral symmetrical congenital isolated ptosis, a condition which is linked to genetic markers on the X chromosome in this family.
CONCLUSION—A pedigree with dominantly inherited congenital bilateral ptosis is presented. The pedigre...

  12. Monoallelic expression on autosomes may explain an unusual heritable form of pigmentary mosaicism: a historical case revisited.

    Science.gov (United States)

    Happle, R

    2009-10-01

    A peculiar observation published in 1971 by Chernosky et al. is revisited in this paper. An African American mother and three of her four children (two girls and one boy) had hyperpigmented skin areas arranged along Blaschko's lines. According to the current knowledge of formal genetics, a mendelian mode of transmission can be excluded, and paradominant inheritance is likewise highly unlikely. The unusual family constellation of pigmentary mosaicism can be best explained as an example of monoallelic autosomal expression, a concept that is now well established in the genetics of plants and animals but so far unexplored in human skin disorders. Either the paternal or the maternal allele is randomly inactivated, therefore this mechanism can be taken as an autosomal counterpart of X-chromosome inactivation. Recent studies suggest that 5-10% of autosomal human genes are monoallelically expressed. This theory opens a new field of research in dermatology. Clinicians should consider this new aetiological concept when observing cases of hereditary cutaneous mosaicism that cannot be explained by X-linkage. PMID:19747340

  13. Nucleolar dominance and ribosomal RNA gene silencing

    OpenAIRE

    Tucker, Sarah; Vitins, Alexa; Pikaard, Craig S.

    2010-01-01

    Nucleolar dominance is an epigenetic phenomenon that occurs in genetic hybrids and describes the expression of 45S rRNA genes inherited from one progenitor due to the silencing of the other progenitor’s rRNA genes. Nucleolar dominance is a manifestation of rRNA gene dosage control, which also occurs in non-hybrids, regulating the number of active rRNA genes according to the cellular demand for ribosomes and protein synthesis. Ribosomal RNA gene silencing involves changes in DNA methylation an...

  14. Current perspectives on mitochondrial inheritance in fungi

    Directory of Open Access Journals (Sweden)

    Xu J

    2015-08-01

    Full Text Available Jianping Xu,1,2 He Li2 1Department of Biology, McMaster University, Hamilton, Canada; 2The Key Laboratory for Non-Wood Forest Cultivation and Conservation of the Federal Ministry of Education, Central South University of Forestry and Technology, Changsha, People’s Republic of China Abstract: The mitochondrion is an essential organelle of eukaryotes, generating the universal energy currency, adenosine triphosphate, through oxidative phosphorylation. However, aside from generation of adenosine triphosphate, mitochondria have also been found to impact a diversity of cellular functions and organ system health in humans and other eukaryotes. Thus, inheriting and maintaining functional mitochondria are essential for cell health. Due to the relative ease of conducting genetic and molecular biological experiments using fungi, they (especially the budding yeast Saccharomyces cerevisiae have been used as model organisms for investigating the patterns of inheritance and intracellular dynamics of mitochondria and mitochondrial DNA. Indeed, the diversity of mitochondrial inheritance patterns in fungi has contributed to our broad understanding of the genetic, cellular, and molecular controls of mitochondrial inheritance and their evolutionary implications. In this review, we briefly summarize the patterns of mitochondrial inheritance in fungi, describe the genes and processes involved in controlling uniparental mitochondrial DNA inheritance in sexual crosses in basidiomycete yeasts, and provide an overview of the molecular and cellular processes governing mitochondrial inheritance during asexual budding in S. cerevisiae. Together, these studies reveal that complex regulatory networks and molecular processes are involved in ensuring the transmission of healthy mitochondria to the progeny. Keywords: uniparental inheritance, biparental inheritance, mating type, actin cable, mitochore, mitochondrial partition 

  15. Inheritance of Arabica Coffee Resistance to Radopholus similisCobb.

    Directory of Open Access Journals (Sweden)

    Retno Hulupi

    2007-05-01

    Full Text Available A research to get inheritance of Arabica coffee resistance to Radopholus similisnematode was done in screen house and laboratory of Indonesian Coffee and Cocoa Research Institute, also at endemic area of coffee plantation, using F1, F1 R and F2 crossing between BP 542 A(resistant x Andungsari 1 (susceptible with their reciprocal, and BP 542 A x Kartika 1. The purpose of this study that was conducted at seedling stage is to formulate a Strategy for Arabica coffee breeding to get resistant varieties to nematode. As the variables of resistance were weight of seedling biomass, percent of root weight deviation, number of root nematodes, number of soil nematodes, reproduction and percent of necrotic root. Using discriminant analysis and fastclus, those data variables were analyzed for genetic of resistance with Statistical Analysis System programme version 8. Genetic study on the inheritance of resistance to R. similiswas started with evaluation of homozigosity of BP 542 A was resistant parent. The result showed that BP 542 A was heterozygous. Therefore, segregation test could not be suggested with segregation pattern principals as Mendel proposed. Segregation test on BP 542 A showed that it was heterozygote and the resistance was controlled by single gene with complete dominant effect, so the progeny segregated in 75% resistant and 25% susceptible. The result of the test showed the absence of maternal effect for root weight deviation and percentage of necrotic root variables, which meant that no cytoplasmic inheritance was involved. Based on the test of segregation ratio, almost all of the resistance was not appropriate for monogenic and or digenic segregation pattern as expected due to non allelic gene interaction that caused epistasis. Key words: Inheritance, resistance, Arabica coffee, Radopholus similis.

  16. Testamental inheritance: Just a legal osmosis?

    Directory of Open Access Journals (Sweden)

    Đorđević-Crnobrnja Jadranka

    2011-01-01

    Full Text Available Bequeath, a dispose of personal property by the last will is an example of intervention of legislation within the complex of customary law. This influence is not unusual but certainly is less frequent than the influence of customary into civil law, especially so in their interaction within inheritance. This paper therefore tries to explain this example of legal osmosis in practice. In addition, the practice in testament inheritance shows also an influence of customary law into legislation. Hence, the paper will also try to discuss a relationship between customary and civil laws and succeeding problems in inheritance at the levels of individual and that of the society.

  17. Autosomal inheritance of diabetes in two families characterized by obesity and a novel H241Q mutation in NEUROD1

    DEFF Research Database (Denmark)

    Gonsorcíková, Lucie; Pruhová, Stepánka; Cinek, Ondrej; Ek, Jakob; Pelikánová, Terezie; Jørgensen, Torben; Eiberg, Hans; Pedersen, Oluf; Hansen, Torben; Lebl, Jan

    BACKGROUND: The aim of the study was to search for mutations in the NEUROD1 and IPF-1 genes in patients with clinical characteristics of maturity-onset diabetes of the young (MODY) but with no mutations in the HNF-4A (MODY1), GCK (MODY2) and TCF1 (MODY3) genes. METHODS: We studied 30 unrelated...

  18. Center for Inherited Disease Research (CIDR)

    Science.gov (United States)

    The Center for Inherited Disease Research (CIDR) Program at The Johns Hopkins University provides high-quality next generation sequencing and genotyping services to investigators working to discover genes that contribute to common diseases.

  19. Inheritance of Resistance to Colletotrichum acutatum in Fragaria x ananassa.

    Science.gov (United States)

    Denoyes-Rothan, Béatrice; Guérin, Guy; Lerceteau-Köhler, Estelle; Risser, Georgette

    2005-04-01

    ABSTRACT Anthracnose, caused by Colletotrichum acutatum, is a major disease of the octoploid cultivated strawberry, Fragaria x ananassa The inheritance of high and intermediate level plant resistances to C. acutatum, pathogenicity group 2, was investigated in an 8 x 8 factorial design. A single dominant gene (Rca2) controlled the high-level resistance, although minor genes may also contribute to resistance in cultivars such as Belrubi. The intermediate level of resistance was quantitative and controlled by minor genes. Analysis of 26 genotypes and cultivars from Fragaria spp. showed that the dominant gene was not rare in the germ plasm of F. x ananassa and that anthracnose resistance was also present in other species of Fragaria. These findings have important implications for anthracnose resistance breeding. PMID:18943043

  20. Inheritance of Humeral Spotting in the Croaking Gourami (Osphronemidae: Trichopsis vittatus)

    OpenAIRE

    Jack S. Frankel*, Lisa Adler-Golden, and Andre N. Porter

    2012-01-01

    The croaking gourami (Trichopsis vittatus) exhibits two phenotypesassociated with humeral spotting. Fish possess aprominent, dark humeral patch or spot located behind theoperculum or lack this spotting pattern. Segregation patternsobserved from the progenies of eleven different crosses supportthe hypothesis that the inheritance of humeral spottingin T. vittatus is controlled by the action of a single autosomallocus, with complete dominance of the allele controlling thespotted phenotype.

  1. Analysis of Multiple Families With Single Individuals Affected by Pseudohypoparathyroidism Type Ib (PHP1B) Reveals Only One Novel Maternally Inherited GNAS Deletion.

    Science.gov (United States)

    Takatani, Rieko; Molinaro, Angelo; Grigelioniene, Giedre; Tafaj, Olta; Watanabe, Tomoyuki; Reyes, Monica; Sharma, Amita; Singhal, Vibha; Raymond, F Lucy; Linglart, Agnès; Jüppner, Harald

    2016-04-01

    Proximal tubular resistance to parathyroid hormone (PTH) resulting in hypocalcemia and hyperphosphatemia are preeminent abnormalities in pseudohypoparathyroidism type Ib (PHP1B), but resistance toward other hormones as well as variable features of Albright's Hereditary Osteodystrophy (AHO) can occur also. Genomic DNA from PHP1B patients shows epigenetic changes at one or multiple differentially methylated regions (DMRs) within GNAS, the gene encoding Gαs and splice variants thereof. In the autosomal dominant disease variant, these methylation abnormalities are caused by deletions in STX16 or GNAS on the maternal allele. The molecular defect(s) leading to sporadic PHP1B (sporPHP1B) remains in most cases unknown and we therefore analyzed 60 sporPHP1B patients and available family members by microsatellite markers, single nucleotide polymorphisms (SNPs), multiplex ligation-dependent probe amplification (MLPA), and methylation-specific MLPA (MS-MLPA). All investigated cases revealed broad GNAS methylation changes, but no evidence for inheritance of two paternal chromosome 20q alleles. Some patients with partial epigenetic modifications in DNA from peripheral blood cells showed more complete GNAS methylation changes when testing their immortalized lymphoblastoid cells. Analysis of siblings and children of sporPHP1B patients provided no evidence for an abnormal mineral ion regulation and no changes in GNAS methylation. Only one patient revealed, based on MLPA and microsatellite analyses, evidence for an allelic loss, which resulted in the discovery of two adjacent, maternally inherited deletions (37,597 and 1427 bp, respectively) that remove the area between GNAS antisense exons 3 and 5, including exon NESP. Our findings thus emphasize that the region comprising antisense exons 3 and 4 is required for establishing all maternal GNAS methylation imprints. The genetic defect(s) leading in sporPHP1B to epigenetic GNAS changes and thus PTH-resistance remains unknown, but it

  2. Asymmetric inheritance of cytoophidia in Schizosaccharomyces pombe

    OpenAIRE

    Jing Zhang; Lydia Hulme; Ji-Long Liu

    2014-01-01

    ABSTRACT A general view is that Schizosaccharomyces pombe undergoes symmetric cell division with two daughter cells inheriting equal shares of the content from the mother cell. Here we show that CTP synthase, a metabolic enzyme responsible for the de novo synthesis of the nucleotide CTP, can form filamentous cytoophidia in the cytoplasm and nucleus of S. pombe cells. Surprisingly, we observe that both cytoplasmic and nuclear cytoophidia are asymmetrically inherited during cell division. Our t...

  3. Probabilistic Logic Programming under Inheritance with Overriding

    OpenAIRE

    Lukasiewicz, Thomas

    2013-01-01

    We present probabilistic logic programming under inheritance with overriding. This approach is based on new notions of entailment for reasoning with conditional constraints, which are obtained from the classical notion of logical entailment by adding the principle of inheritance with overriding. This is done by using recent approaches to probabilistic default reasoning with conditional constraints. We analyze the semantic properties of the new entailment relations. We also present algorithms ...

  4. INHERITED SKILLS AND TECHNOLOGY: INDIAN ENTREPRENEURSHIP DEVELOPMENT

    OpenAIRE

    GANESH S. HEGDE; N. S. NARAHARI

    2009-01-01

    Entrepreneurial development in India relies on generational mentoring, family business skill set, and exploration of technological progress. The know-how of skills, learned and refined over generations, leads to sustained development that is then converted into technology. Inheritance is one aspect that plays a major role in skill development. The transformation of skill into a technological component paves the way for the successful entrepreneurship. The spark initiated through inherited ski...

  5. Spectrum of Autosomal Recessive Congenital Ichthyosis in Scandinavia

    DEFF Research Database (Denmark)

    Hellström Pigg, Maritta; Bygum, Anette; Gånemo, Agneta; Virtanen, Marie; Brandrup, Flemming; Zimmer, Andreas D; Hotz, Alrun; Vahlquist, Anders; Fischer, Judith

    2016-01-01

    Autosomal recessive congenital ichthyosis (ARCI) represents a heterogeneous group of rare disorders of cornification with 3 major subtypes: harlequin ichthyosis (HI), lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE). A 4th subtype has also been proposed: pleomorphic...

  6. X Chromosome and Autosome Dosage Responses in Drosophila melanogaster Heads.

    Science.gov (United States)

    Chen, Zhen-Xia; Oliver, Brian

    2015-06-01

    X chromosome dosage compensation is required for male viability in Drosophila. Dosage compensation relative to autosomes is two-fold, but this is likely to be due to a combination of homeostatic gene-by-gene regulation and chromosome-wide regulation. We have baseline values for gene-by-gene dosage compensation on autosomes, but not for the X chromosome. Given the evolutionary history of sex chromosomes, these baseline values could differ. We used a series of deficiencies on the X and autosomes, along with mutations in the sex-determination gene transformer-2, to carefully measure the sex-independent X-chromosome response to gene dosage in adult heads by RNA sequencing. We observed modest and indistinguishable dosage compensation for both X chromosome and autosome genes, suggesting that the X chromosome is neither inherently more robust nor sensitive to dosage change. PMID:25850426

  7. Prevention of bleeding and hemorrhagic complications in surgical patients with inherited factor VII deficiency.

    Science.gov (United States)

    Wiszniewski, Adam; Szczepanik, Andrzej; Misiak, Andrzej; Bykowska, Ksenia; Szopiński, Piotr

    2015-04-01

    Inherited factor VII (FVII) deficiency is a rare autosomal recessive hemorrhagic disorder. The major clinical symptoms include: bleeding from the oral cavity, epistaxis, menorrhagia, spontaneous hemarthros, bleeding to the gastrointestinal tract and central nervous system, and perioperative bleeding. The aim of this study was to present our experience in preventing bleeding and hemorrhagic disorders in surgical patients with inherited FVII deficiency by using recombinant activated FVIIa (rFVIIa), and with prothrombin complex concentrates (PCCs). In 2002-2011, 17 patients with inherited FVII deficiency underwent surgery. Thirteen patients had isolated FVII deficiency below 10%, and four patients 10-25. To prevent bleeding and hemorrhagic complications, we administered small single doses of rFVIIa (Novo-Seven) at 12-h intervals to 15 patients on surgery day and on day 1 following surgery, then every 24 h; PCCs were administered (Prothromplex, Beriplex) to two patients. No symptoms of bleeding, hemorrhagic or thromboembolic complications were observed in the perioperative and 1-month observation period in surgical patients treated with rFVIIa. One patient treated with PCC (Prothromplex) developed distal deep vein thrombosis on postoperative day 7. The results suggest that small, single, every 12-h doses of rFVIIa (NovoSeven) and in next days after surgery one time every 24 h are well tolerated and effective for prevention of thromboembolic, bleeding and hemorrhagic complications in FVII-deficient patients. Antithrombotic prophylaxis with low-molecular-weight heparin should be applied in patients using PCCs. PMID:25688458

  8. Chromosome landmarks and autosome-sex chromosome translocations in Rumex hastatulus, a plant with XX/XY1Y2 sex chromosome system.

    Science.gov (United States)

    Grabowska-Joachimiak, Aleksandra; Kula, Adam; Książczyk, Tomasz; Chojnicka, Joanna; Sliwinska, Elwira; Joachimiak, Andrzej J

    2015-06-01

    Rumex hastatulus is the North American endemic dioecious plant with heteromorphic sex chromosomes. It is differentiated into two chromosomal races: Texas (T) race characterised by a simple XX/XY sex chromosome system and North Carolina (NC) race with a polymorphic XX/XY1Y2 sex chromosome system. The gross karyotype morphology in NC race resembles the derived type, but chromosomal changes that occurred during its evolution are poorly understood. Our C-banding/DAPI and fluorescence in situ hybridization (FISH) experiments demonstrated that Y chromosomes of both races are enriched in DAPI-positive sequences and that the emergence of polymorphic sex chromosome system was accompanied by the break of ancestral Y chromosome and switch in the localization of 5S rDNA, from autosomes to sex chromosomes (X and Y2). Two contrasting domains were detected within North Carolina Y chromosomes: the older, highly heterochromatinised, inherited from the original Y chromosome and the younger, euchromatic, representing translocated autosomal material. The flow-cytometric DNA estimation showed ∼3.5 % genome downsizing in the North Carolina race. Our results are in contradiction to earlier reports on the lack of heterochromatin within Y chromosomes of this species and enable unambiguous identification of autosomes involved in the autosome-heterosome translocation, providing useful chromosome landmarks for further studies on the karyotype and sex chromosome differentiation in this species. PMID:25394583

  9. Inheritance Pattern of Temephos Resistance, an Organophosphate Insecticide, in Aedes aegypti (L.).

    Science.gov (United States)

    Shetty, Vinaya; Sanil, Deepak; Shetty, N J

    2015-01-01

    The present paper reports the mode of inheritance of resistance in laboratory induced temephos resistant and susceptible strains of Ae. aegypti. Homozygous resistant and susceptible strains of Ae. aegypti were generated by selective inbreeding at a diagnostic dose of 0.02 mg/L of temephos. Genetic crosses were carried out between these strains to determine the inheritance pattern of temephos resistance. The log-dosage probit mortality relationships and degree of dominance (D) were calculated. The dosage-mortality (d-m) line of the F 1 generation was nearer to the resistant parent than the susceptible one. The "D" value was calculated as 0.15 indicating that the temephos resistant gene is incompletely dominant. The d-m lines of the F 2 generation and progeny from the backcross exhibited clear plateaus of mortality across a range of doses indicating that temephos resistance is controlled by a single gene. Comparison of the mortality data with the theoretical expectations using the χ (2) test revealed no significant difference, confirming a monogenic pattern of inheritance. In conclusion, the study provides evidence that the temephos resistance in Ae. aegypti follows an incompletely dominant and monogenic mode of inheritance. PMID:25861478

  10. Inheritance of culm height and grain yield in durum wheat

    International Nuclear Information System (INIS)

    Results from a study of GA sensitive and GA insensitive durum wheat mutants and cultivars in relation with their culm height and 1000 grain weight are presented. With increasing culm height, the GA response also increased. A positive correlation between plant height and GA response was found. Crosses were made between durum wheats and the F1 and F2 progenies were analysed. A different inheritance in F1 and segregation in F2 was obtained in crosses of a semi-dwarf, GA insensitive [1] line with GA sensitive (S) lines differing in height, medium (93.2cm) and tall (133.5cm). In a reciprocal cross, semi-dwarf - I with medium - S, the semi-dwarf type was dominant in F1, suggesting that their semi-dwarfing genes were not allelic. When the semi-dwarf - I and tall - S were crossed an intermediate inheritance in F1 was observed. In the F2 generation from crosses semi-dwarf - I with medium - S with semi-dwarf - I, a phenotypic dihybred segregation 9:3:3:1 was observed. In crosses semi-dwarf - I with tall - S different variation curves were obtained. Semi-dwarfs with high productivity were observed in F2, a fact indicating that lodging resistant lines with high yields could be selected. (author)

  11. Anaesthetic management of a child with congenital afibrinogenemia - A rare inherited coagulation disorder

    Directory of Open Access Journals (Sweden)

    Sham Sunder Goyal

    2011-01-01

    Full Text Available Congenital afibrinogenemia is a very rare autosomal recessive disorder, results from mutation that affects plasma fibrinogen concentration. It is frequently associated with bleeding diathesis of varying severity. We describe the case of a 10-year-old child diagnosed of congenital afibrinogenemia who presented to hospital with subperiosteal haematoma and was posted for incision and drainage. Replacement therapy is the mainstay of treatment of bleeding episodes in this patient and plasma-derived fibrinogen concentrate is the agent of choice. Cryoprecipitate and fresh frozen plasma are alternative treatments. Appropriate amount of cryoprecipitate were transfused pre-operatively to the child. Individuals with congenital afibrinogenemia should be managed by a comprehensive bleeding disorder care team experienced in diagnosing and managing inherited bleeding disorders. Anaesthesiologist, surgeons and haematologist should work like a unit to manage the surgical emergencies.

  12. Posible origen hereditario de una Hipospadias que afecta a corderos con un alto grado de consanguinidad (Inherited origin suggested for hypospadias affecting to lambs with a low inbreeding coefficient.

    Directory of Open Access Journals (Sweden)

    Tejedor-Hernández, T

    2009-05-01

    Full Text Available Resumen1Departamento de Patología Animal. Facultad de Veterinaria.Universidad de Zaragoza. 2Departamento de Anatomía, Embriología y Genética Animal. Facultad de Veterinaria. Universidad de Zaragoza.E-mail: mailto:martaborofri@hotmail.com La hipospadias es una de las anomalías más frecuentes que afecta al pene en humanos. Se considera que su origen tiene una base genética y se han propuesto varios modelos de herencia: autosómica recesiva, autosómica dominante, ligada al cromosoma X o un patrón de herencia complejo con un índice de heredabilidad de 0,99. Existen factores ambientales como elbajo peso al nacimiento, los tratamientos hormonales o la exposición afactores que alteren los patrones hormonales durante la gestación, quepueden afectar a esta patología.En esta comunicación se presenta un estudio detallado de dos casos de hipospadias en corderos macho. Ambos estaban asociados a consanguinidad, especialmente uno de ellos, que tenía un 37,5% de coeficiente de consanguinidad. No se encontró ningún factor ambiental que pudiera ser el desencadenante de esta patología, lo que hace sospechar un origen genético. Esta circunstancia permitiría su utilización como modelo animal para el estudio de las etiologías de la hipospadias en el hombre. Un análisis preliminar del segundo exón de la 5-α reductasa 2 no proporcionó evidencias de mutaciones en estos corderos. SummaryHypospadias are the most frequent human penile abnormality. They areconsidered to have a genetic basis, and several inheritance models areproposed: recessive autosomal, dominant autosomal, linked to the Xchromosome or a complex inheritance pattern presenting a 0,99heritability index. Environmental factors such as low birth weight,hormonal treatments and exposure to endocrine disruptors duringpregnancy can also be involved in this pathology.The authors present a detailed study of two cases of hypospadias in male lambs. Both cases were associated to consanguinity

  13. Towards unifying inheritance and automatic program specialization

    DEFF Research Database (Denmark)

    Schultz, Ulrik Pagh

    2002-01-01

    inheritance with covariant specialization to control the automatic application of program specialization to class members. Lapis integrates object-oriented concepts, block structure, and techniques from automatic program specialization to provide both a language where object-oriented designs can be e...

  14. A Feingold syndrome case with previously undescribed features and a new mutation.

    NARCIS (Netherlands)

    Kocak, H.; Ozaydin, E.; Kose, G.; Marcelis, C.L.M.; Kamsteeg, E.J.; Ceylaner, S.

    2009-01-01

    Feingold syndrome (FS) is a dominantly inherited combination of microcephaly with or without learning disabilities, hand and foot abnormalities, short palpebral fissures and esophageal/duodenal atresia. The syndrome has autosomal dominant inheritance with full penetrance, and variable expressivity.

  15. Topics on domination

    CERN Document Server

    Hedetniemi, ST

    1991-01-01

    The contributions in this volume are divided into three sections: theoretical, new models and algorithmic. The first section focuses on properties of the standard domination number &ggr;(G), the second section is concerned with new variations on the domination theme, and the third is primarily concerned with finding classes of graphs for which the domination number (and several other domination-related parameters) can be computed in polynomial time.

  16. Total well dominated trees

    DEFF Research Database (Denmark)

    Finbow, Arthur; Frendrup, Allan; Vestergaard, Preben D.

    cardinality then G is a total well dominated graph. In this paper we study composition and decomposition of total well dominated trees. By a reversible process we prove that any total well dominated tree can both be reduced to and constructed from a family of three small trees....

  17. Epidermolysis bullosa, dominant dystrophic (image)

    Science.gov (United States)

    This picture shows skin lesions (epidermolysis bullosa) over the joints on the hands and feet (interphalangeal joints). Dystrophic epidermolysis bullosa is an inherited condition that causes red blisters ( ...

  18. The ADAMTS18 gene is responsible for autosomal recessive early onset severe retinal dystrophy

    Directory of Open Access Journals (Sweden)

    Peluso Ivana

    2013-01-01

    Full Text Available Abstract Background Inherited retinal dystrophies, including Retinitis Pigmentosa and Leber Congenital Amaurosis among others, are a group of genetically heterogeneous disorders that lead to variable degrees of visual deficits. They can be caused by mutations in over 100 genes and there is evidence for the presence of as yet unidentified genes in a significant proportion of patients. We aimed at identifying a novel gene for an autosomal recessive form of early onset severe retinal dystrophy in a patient carrying no previously described mutations in known genes. Methods An integrated strategy including homozygosity mapping and whole exome sequencing was used to identify the responsible mutation. Functional tests were performed in the medaka fish (Oryzias latipes model organism to gain further insight into the pathogenic role of the ADAMTS18 gene in eye and central nervous system (CNS dysfunction. Results This study identified, in the analyzed patient, a homozygous missense mutation in the ADAMTS18 gene, which was recently linked to Knobloch syndrome, a rare developmental disorder that affects the eye and the occipital skull. In vivo gene knockdown performed in medaka fish confirmed both that the mutation has a pathogenic role and that the inactivation of this gene has a deleterious effect on photoreceptor cell function. Conclusion This study reveals that mutations in the ADAMTS18 gene can cause a broad phenotypic spectrum of eye disorders and contribute to shed further light on the complexity of retinal diseases.

  19. Inherited Fuzzy Interpolation Based on the Inherited Lower-upper Factorization

    Directory of Open Access Journals (Sweden)

    M.A. Fariborzi Araghi

    2014-12-01

    Full Text Available In this paper, a new scheme is proposed to find the fuzzy interpolation polynomial. In this case, the nodes are crisp data and the values are fuzzy numbers. In order to obtain the interpolation polynomial, a linear system is solved with crisp coefficients matrix and fuzzy right hand side. Then, the inherited lower-upper (LU triangular factorization and inherited interpolation are applied to solve this system. The examples illustrate the applicability, simplicity and efficiency of the proposed method.

  20. Inherited Fuzzy Interpolation Based on the Inherited Lower-upper Factorization

    OpenAIRE

    M. A. Fariborzi Araghi; A. Fallahzadeh

    2014-01-01

    In this paper, a new scheme is proposed to find the fuzzy interpolation polynomial. In this case, the nodes are crisp data and the values are fuzzy numbers. In order to obtain the interpolation polynomial, a linear system is solved with crisp coefficients matrix and fuzzy right hand side. Then, the inherited lower-upper (LU) triangular factorization and inherited interpolation are applied to solve this system. The examples illustrate the applicability, simplicity and efficiency of the propose...