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Sample records for alport syndrome molecular

  1. Alport Syndrome Diagnosis

    Science.gov (United States)

    ... with X-linked Alport Syndrome will show abnormal staining for COL4A5 in the skin biopsy. This approach ... and enzyme tests are performed on cultured tissue cells and/or white blood cells. During amniocentesis, a ...

  2. Alport Syndrome

    Science.gov (United States)

    ... syndrome diagnosed? Your healthcare provider will have to watch your signs, symptoms, and look at your family ... 05/2016 - 10:00am Philadelphia, PA Kidney Camp Sun, 07/17/2016 - 6:00pm Ingleside, IL Register ...

  3. [Alport's syndrome (author's transl)].

    Science.gov (United States)

    Huismans, H

    1978-05-01

    A case report is given of a 22-years old student (whose brother had Alport's syndrome) with recurrent central corneal swelling and paracentral erosions of the cornea of both eyes. Further signs of beginning Alport's syndrome in this case are disturbance of re-adaptation after dazzling (Mesoptometer) and paracentral scotomata in the visual fields. Remarkable was the small diameter of the disc in both eyes (1.37 mm). Local therapy was Scopolamin-eye-drops, Actihaemyl- and especially Cystein-Gel (2.4%). PMID:672101

  4. Alport Syndrome Foundation

    Science.gov (United States)

    ... Donate Donate Fundraising & Events Matching Gifts Planned Gifts Organ Donation Annual Campaign Healthy Kidneys Annual Campaign Donors Blog ... Donate Now Fundraising & Events Matching Gifts Planned Gifts Organ Donation Past Events Upcoming Events Resources Stay Connected Alport ...

  5. X-linked Alport syndrome

    DEFF Research Database (Denmark)

    Jais, J P; Knebelmann, B; Giatras, I;

    2000-01-01

    Alport syndrome (AS) is a type IV collagen hereditary disease characterized by the association of progressive hematuric nephritis, hearing loss, and, frequently, ocular changes. Mutations in the COL4A5 collagen gene are responsible for the more common X-linked dominant form of the disease. Consid...

  6. X-linked Alport syndrome

    DEFF Research Database (Denmark)

    Jais, Jean Philippe; Knebelmann, Bertrand; Giatras, Iannis;

    2003-01-01

    Alport syndrome (AS) is a type IV collagen hereditary disease characterized by progressive hematuric nephritis, hearing loss, and ocular changes. Mutations in the COL4A5 collagen gene are responsible for the more common X-linked dominant form of the disease characterized by much less severe disea...

  7. Kidney Transplantation in Patients With Alport Syndrome

    Directory of Open Access Journals (Sweden)

    Hassan Ahmadnia

    2007-02-01

    Full Text Available Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Introduction: The aim of this study was to evaluate the results of kidney transplantation in patients with Alport syndrome. Materials and Methods: A total of 15 patients with Alport syndrome underwent kidney transplantation and the result of their transplantation was compared with the results in patients without Alport Syndrome. Rejection episodes and the presence of antiglomerular basement membrane (anti-GBM nephritis were assessed in these patients. Results: Fifteen patients with Alport syndrome were compared with a control group including 212 kidney allograft recipients. One patient with Alport syndrome (6.7% and 30 controls (14.2% experienced delayed graft function. Renal artery thrombosis was reported in 1 patient (6.7% with Alport syndrome and 10 (4.7% in the control group, which led to nephrectomy in all cases. Acute rejection was confirmed in 2 patients (13.3% by kidney biopsy and classic treatment yielded relative response. However, they lost their grafts 35 and 44 months after the transplantation. On pathologic examination, no specific finding of anti-GBM nephritis was found. In the control group, 43 cases of acute rejection (20.3% were reported and 12 patients (5.7% returned to dialysis. The 1-, 3-, and 5-year

  8. Skin Biopsy for the diagnosis of Alport Syndrome

    OpenAIRE

    Lagona, E; Tsartsali, L; Kostaridou, S; Skiathitou, A; Georgaki, E; Sotsiou, F

    2008-01-01

    Alport syndrome (AS) is the most common hereditary nephritis often associated with extrarenal manifestations. It was first described by Alport on 1927. There is a primary disorder in collagen type IV which is the main component of the basement membranes. Alport syndrome is more frequently inherited as an X-linked and less commonly as an autosomal dominant or autosomal recessive trait. We describe the case of a 3-year-old boy with the X-linked variant of AS. The diagnosis was at first speculat...

  9. Association of Alport's syndrome with HLA-DR2 antigen in a group of unrelated patients

    Directory of Open Access Journals (Sweden)

    E.A. Donadi

    1998-04-01

    Full Text Available A few family studies have evaluated HLA antigens in Alport's syndrome; however, there are no large population studies. In the present report, we studied 40 unrelated white patients with Alport's syndrome seen at the Unit of Renal Transplantation, Faculty of Medicine of Ribeirão Preto, São Paulo, Brazil. HLA-A, -B, -DR and -DQ antigens were typed using a complement-dependent microlymphocytotoxicity assay. A control white population (N = 403 from the same geographical area was also typed for HLA antigens. Although the frequencies of HLA-A and -B antigens of patients were not statistically different from controls, the frequency of HLA-DR2 antigen observed in patients (65% was significantly increased in relation to controls (26%; P<0.001. The relative risk and etiologic fraction for HLA-DR2 antigen were 5.2 and 0.525, respectively. Although few immunological abnormalities have been shown in Alport's syndrome, in this report we emphasize the association of HLA molecules and Alport's syndrome. Besides the well-known inherited molecular defects encoded by type IV collagen genes in Alport's syndrome, the major histocompatibility alleles may be in linkage disequilibrium with these defective collagen genes

  10. Choosing a mouse model to study the molecular pathobiology of Alport glomerulonephritis.

    Science.gov (United States)

    Cosgrove, D; Kalluri, R; Miner, J H; Segal, Y; Borza, D-B

    2007-04-01

    Alport syndrome, caused by mutations that interfere with the normal assembly of the alpha3alpha4alpha5(IV) collagen network in the glomerular basement membrane (GBM), is the most common inherited glomerular disease leading to renal failure. A detailed knowledge of the underlying pathogenic mechanisms is necessary for developing new, more specific, and effective therapeutic strategies aimed at delaying the onset and slowing disease progression. Studies of several dog and mouse models of Alport syndrome have significantly enhanced our understanding of the disease mechanisms and provided systems for testing potential therapies. In the most widely used Col4a3-/- mouse models of autosomal-recessive Alport syndrome (ARAS), the genetic background strongly affects renal survival. One contributing factor may be the strong ectopic deposition of alpha5alpha6(IV) collagen in the GBM of Col4a3-/- mice on the C57BL/6J background, which is almost undetectable on the 129/Sv background. This isoform 'switch' has not been observed in human ARAS, although it had been reported in the dog model of ARAS. In human patients as well as dog and mouse models of X-linked Alport syndrome, the alpha3-alpha6(IV) collagen chains are absent from the GBM. These biochemical differences among Alport animal models provide an opportunity to determine how the molecular makeup of the GBM affects the glomerular function. At the same time, potentially confounding influences of characteristics unique to a particular strain or model should be carefully considered in the design of studies aiming to define key events underlying the pathobiology of Alport glomerular disease. PMID:17290292

  11. Multipoint linkage analysis in X-linked Alport syndrome

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Kruse, T A; Thomsen, A; Spencer, E S

    1991-01-01

    In order to localize the gene for the X-linked form of Alport syndrome (ATS) more precisely, we performed restriction fragment length polymorphism analysis with nine different X-chromosomal DNA markers in 107 members of twelve Danish families segregating for classic ATS or progressive hereditary ...

  12. Type IV renal tubular acidosis associated with Alport's syndrome.

    OpenAIRE

    Tkácová, R.; Roland, R.; Böör, A.; Kovácová, A.; Lazúrová, I.; Tkác, I.; Hildebrand, T.; Sefara, P.

    1993-01-01

    A case of hereditary nephritis with mild reduction of renal function associated with renal tubular acidosis type IV is described. The patient was admitted with life-threatening hyperkalaemia. To our knowledge, type IV renal tubular acidosis has not been reported previously in association with Alport's syndrome in an adult patient.

  13. Albumin contributes to kidney disease progression in Alport syndrome.

    Science.gov (United States)

    Jarad, George; Knutsen, Russell H; Mecham, Robert P; Miner, Jeffrey H

    2016-07-01

    Alport syndrome is a familial kidney disease caused by defects in the collagen type IV network of the glomerular basement membrane. Lack of collagen-α3α4α5(IV) changes the glomerular basement membrane morphologically and functionally, rendering it leaky to albumin and other plasma proteins. Filtered albumin has been suggested to be a cause of the glomerular and tubular injuries observed at advanced stages of Alport syndrome. To directly investigate the role that albumin plays in the progression of disease in Alport syndrome, we generated albumin knockout (Alb(-/-)) mice to use as a tool for removing albuminuria as a component of kidney disease. Mice lacking albumin were healthy and indistinguishable from control littermates, although they developed hypertriglyceridemia. Dyslipidemia was observed in Alb(+/-) mice, which displayed half the normal plasma albumin concentration. Alb mutant mice were bred to collagen-α3(IV) knockout (Col4a3(-/-)) mice, which are a model for human Alport syndrome. Lack of circulating and filtered albumin in Col4a3(-/-);Alb(-/-) mice resulted in dramatically improved kidney disease outcomes, as these mice lived 64% longer than did Col4a3(-/-);Alb(+/+) and Col4a3(-/-);Alb(+/-) mice, despite similar blood pressures and serum triglyceride levels. Further investigations showed that the absence of albumin correlated with reduced transforming growth factor-β1 signaling as well as reduced tubulointerstitial, glomerular, and podocyte pathology. We conclude that filtered albumin is injurious to kidney cells in Alport syndrome and perhaps in other proteinuric kidney diseases, including diabetic nephropathy. PMID:27147675

  14. Diffuse esophageal leiomyomatosis in a child with alport syndrome: case report

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Hong Seok; Goo, Hyun Woo; Yoon, Chong Hyun [Asan Medical Center, Seoul (Korea, Republic of)

    2004-05-01

    Diffuse esophageal leiomyomatosis is an exceedingly rare, benign, neoplastic condition occurring predominantly in children and young adults. This condition may occur as an isolated finding, or it may be associated with Alport syndrome. We report a case of diffuse esophageal leiomyomatosis with Alport syndrome in a 5-year-old girl who had presented with recurrent pneumonia, and present a review of the literature. We suspected Alport syndrome in the patient because she had a clinical history of congenital cataracts and hematuria, as well as imaging findings of diffuse esophageal leiomyomatosis. Alport syndrome was subsequently confirmed by electron microscopy of the kidney.

  15. Diffuse esophageal leiomyomatosis in a child with alport syndrome: case report

    International Nuclear Information System (INIS)

    Diffuse esophageal leiomyomatosis is an exceedingly rare, benign, neoplastic condition occurring predominantly in children and young adults. This condition may occur as an isolated finding, or it may be associated with Alport syndrome. We report a case of diffuse esophageal leiomyomatosis with Alport syndrome in a 5-year-old girl who had presented with recurrent pneumonia, and present a review of the literature. We suspected Alport syndrome in the patient because she had a clinical history of congenital cataracts and hematuria, as well as imaging findings of diffuse esophageal leiomyomatosis. Alport syndrome was subsequently confirmed by electron microscopy of the kidney

  16. Ocular features in Alport syndrome: pathogenesis and clinical significance.

    Science.gov (United States)

    Savige, Judy; Sheth, Shivanand; Leys, Anita; Nicholson, Anjali; Mack, Heather G; Colville, Deb

    2015-04-01

    Alport syndrome is an inherited disease characterized by progressive renal failure, hearing loss, and ocular abnormalities. Mutations in the COL4A5 (X-linked), or COL4A3 and COL4A4 (autosomal recessive) genes result in absence of the collagen IV α3α4α5 network from the basement membranes of the cornea, lens capsule, and retina and are associated with corneal opacities, anterior lenticonus, fleck retinopathy, and temporal retinal thinning. Typically, these features do not affect vision or, in the case of lenticonus, are correctable. In contrast, the rarer ophthalmic complications of posterior polymorphous corneal dystrophy, giant macular hole, and maculopathy all produce visual loss. Many of the ocular features of Alport syndrome are common, easily recognizable, and thus, helpful diagnostically, and in identifying the likelihood of early-onset renal failure. Lenticonus and central fleck retinopathy strongly suggest the diagnosis of Alport syndrome and are associated with renal failure before the age of 30 years, in males with X-linked disease. Sometimes, ophthalmic features suggest the mode of inheritance. A peripheral retinopathy in the mother of a male with hematuria suggests X-linked inheritance, and central retinopathy or lenticonus in a female means that recessive disease is likely. Ocular examination, retinal photography, and optical coherence tomography are widely available, safe, fast, inexpensive, and acceptable to patients. Ocular examination is particularly helpful in the diagnosis of Alport syndrome when genetic testing is not readily available or the results are inconclusive. It also detects complications, such as macular hole, for which new treatments are emerging. PMID:25649157

  17. Ocular, Ear and Renal Manifestations of Alport Syndrome in Three Iranian Families

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Davari

    2014-12-01

    Full Text Available Alport syndrome is a genetic disorder of basement membranes caused by mutations in type IV collagen network. It was first identified by Dr. Alport in 1927. Its major clinical manifestations are included: glomerulopathy, sensory hearing loss, anterior lenticonus, and the prevalence of Alports’ gene in general population is about 1 in 5000 and the disease prevalence is 1 in 10000 [1-3]. Here we report ocular, ear and renal manifestations of Alport syndrome in 3 families that living in the east city of Iran, Birjand, and we have followed all of this family for 6 years so far.

  18. Surgical Management of Anterior Lenticonus in a Patient with Alport´s Syndrome

    OpenAIRE

    Can, Çiğdem Ülkü; İlhan, Bayazıt; Sibel POLAT

    2008-01-01

    Background: To discuss ophthalmic features and management of a patient with Alport´s syndrome and anterior lenticonus. Materials and Methods: A 22-year-old female patient with Alport´s syndrome who, in another center, had undergone laser in situ keratomileusis (LASIK) because of high myopia was determined to have bilateral anterior lenticonus. We treated the other eye by phacoemulsification and intraocular lens (IOL) implantation. Results: Lens extraction and IOL implantation gave satisfact...

  19. Alport syndrome. Molecular genetic aspects

    DEFF Research Database (Denmark)

    Hertz, Jens Michael

    2009-01-01

    of the study methods were set up for detection and characterisation of mutations in the COL4A5 gene in 135 patients suspected of AS. The aims of that part of the study were to develop an efficient and reliable approach for mutation detection, and to implement the results of the mutation analysis in clinical...... in heterozygous form will not be detected by PCR-SSCP or direct sequencing. A method based on the PCR-SSCP technique was set up for screening of the COL4A5 gene exon-by-exon for mutation. All 51 COL4A5 exons with flanking intronic sequences were screened by this technique. The two alternatively transcribed exons...... 41A and 41B were directly sequenced. The PCR-SSCP method was compared to direct sequencing in 15 of the cases. No difference in mutation detection rates were found. Finally, a method based on RT-PCR analysis of mRNA extracted from cultured skin fibroblasts was established. A mutation in a patient...

  20. An Overlapping Case of Alport Syndrome and Thin Basement Membrane Disease

    Science.gov (United States)

    Alganabi, Mashriq; Eter, Ahmad

    2016-01-01

    We report a case of a 48-year-old male who presented with hematuria of at least 10 years, and has a daughter with hematuria as well. The patient has a history of degenerative hearing loss, decreased vision and cataract formation, but no diabetes, hypertension or proteinuria. A full serology and urology workup was negative for any abnormality. A kidney biopsy for the patient revealed a diagnosis of Alport syndrome but was unable to rule out thin basement membrane disease. The biopsy was inconclusive in making the diagnosis but the patient’s clinical presentation led to the diagnosis of Alport syndrome. The patient’s 10-year-old daughter also has hematuria with no clear etiology but now can subsequently be anticipatorily managed for Alport syndrome progression. Due to the rarity of the disease, diagnosis is often missed or delayed by primary care providers especially when no associated proteinuria has yet developed. This can lead to confusion and misdiagnosis with thin basement membrane disease, a generally benign hematuria without kidney failure progression. Additionally, biopsy can be inconclusive in these patients, relying on the physician’s history and physical examination findings to diagnose. It is important to appropriately diagnose Alport syndrome not only to manage the patient’s rate of kidney failure progression but also allow for a higher degree of suspicion, screening and intervention in the patient’s family members. Both the inconclusive nature of kidney biopsies and the usefulness of diagnosis for family member screening are often overlooked in medical literature but are explored in this case.

  1. The inner ear of dogs with X-linked nephritis provides clues to the pathogenesis of hearing loss in X-linked Alport syndrome.

    Science.gov (United States)

    Harvey, S J; Mount, R; Sado, Y; Naito, I; Ninomiya, Y; Harrison, R; Jefferson, B; Jacobs, R; Thorner, P S

    2001-09-01

    Alport syndrome is an inherited disorder of type IV collagen with progressive nephropathy, ocular abnormalities, and high-tone sensorineural deafness. In X-linked Alport syndrome, mutations in the COL4A5 gene encoding the alpha5 chain of type IV collagen lead to loss of the alpha3/alpha4/alpha5 network and increased susceptibility of the glomerular basement membrane to long-term damage. The molecular defects that underlie the otopathology in this disease remain poorly understood. We used a canine model of X-linked Alport syndrome to determine the expression of type IV collagen alpha-chains in the inner ear. By 1 month in normal adult dogs, the alpha3, alpha4, and alpha5 chains were co-expressed in a thin continuous line extending along the basilar membrane and the internal and external sulci, with the strongest expression along the lateral aspect of the spiral ligament in the basal turn of the cochlea. Affected dogs showed complete absence of the alpha3/alpha4/alpha5 network. The lateral aspect of the spiral ligament is populated by tension fibroblasts that express alpha-smooth muscle actin and nonmuscle myosin and are postulated to generate radial tension on the basilar membrane via the extracellular matrix for reception of high frequency sound. We propose that in Alport syndrome, the loss of the alpha3/alpha4/alpha5 network eventually weakens the interaction of these cells with their extracellular matrix, resulting in reduced tension on the basilar membrane and the inability to respond to high frequency sounds. PMID:11549602

  2. Clear lens phacoemulsification in the anterior lenticonus due to Alport Syndrome: two case reports

    Directory of Open Access Journals (Sweden)

    Aslanzadeh Ghassem

    2008-05-01

    Full Text Available Abstract Introduction Alport Syndrome has a prevalence of 1 case per 5,000 people and 85% of patients have the X-linked form, where affected males develop renal failure and usually have high-tone sensorineural deafness by age 20. The main abnormality is deficient synthesis of type IV collagen, the main component of basement membranes. Common ocular abnormalities of this syndrome consist of dot-and-fleck retinopathy, posterior polymorphous corneal dystrophy, and anterior lenticonus, but other ocular defects such as cataracts, posterior lenticonus, and retinal detachments have also been reported. Case presentation We report two cases of anterior lenticonus due to Alport Syndrome and describe clear lens phacoemulsification and foldable intraocular lens implantation as an effective and safe refractive procedure in the four eyes of these two patients. Conclusion All four eyes of the two patients were in good condition after surgery and achieved satisfactory optical and visual results and had no remarkable complications at six-months follow-up. Clear lens phacoemulsification with foldable intraocular lens implantation can be used as an efficient and safe procedure for vision disorders in these patients.

  3. Mutation in the alpha 5(IV) collagen chain in juvenile-onset Alport syndrome without hearing loss or ocular lesions

    DEFF Research Database (Denmark)

    Zhou, J; Hertz, Jens Michael; Tryggvason, K

    1992-01-01

    A single base mutation was identified in the type IV collagen alpha 5 chain gene (COL4A5) of a Danish kindred with Alport syndrome. The 27-year-old male proband developed hematuria in childhood and terminal renal failure at the age of 25 years. He has no hearing loss or ocular lesions. Electron...

  4. Revisão sobre a perda auditiva na Síndrome de Alport, analisando os aspectos clínicos, genéticos e biomoleculares Revision about hearing loss in the Alport's syndrome, analyzing the clinical, genetic and bio-molecular aspects

    Directory of Open Access Journals (Sweden)

    Fátima R. A. Alves

    2005-12-01

    Full Text Available A Síndrome de Alport é uma desordem hereditária, caracterizada por hematúria, freqüentemente levando à falência renal. Pode ser acompanhada de alterações extra-renais, tais como: perda auditiva (PA sensório-neural e alterações oculares. São descritas formas dominantes ligadas ao X, devidas às mutações no lócus COL4A5 e uma forma autossômica recessiva resultando de mutações no lócus COL4A3 ou COL4A4. Ainda foi sugerido um tipo autossômico dominante de SA. A doença decorre de alterações nas cadeias de colágeno tipo IV e os sintomas refletem o comprometimento da membrana basal de vários órgãos. As redes alfa3.alfa4.alfa5(IV ocorrem no rim, na cóclea e no olho. O objetivo foi caracterizar a PA neste grupo de pacientes. Quando o quadro progride para o estágio final de falência renal, o melhor método de tratamento é o transplante, que tem contribuído para o aumento da sobrevida. Nesta revisão bibliográfica, observamos que: 1. A SA caracteriza-se por hematúria, que evolui para falência renal e pode ser acompanhada de manifestações extra-renais. A PA é um achado extra-renal freqüente e um dos primeiros sintomas na SA, sendo um fator relevante para o prognóstico da evolução da doença renal; 2. A SA é genética e decorre da alteração das cadeias do colágeno tipo IV nas membranas basais; 3. A perda auditiva na SA é sensório-neural, de intensidade variável, progressiva e simétrica. Acomete as freqüências médias e altas; 4. Na investigação das perdas auditivas, o otorrinolaringologista deve incluir um exame de urina. É fundamental que o otologista atue no acompanhamento deste grupo de pacientes.Alport Syndrome is a genetic disorder characterized by hematuria, which often leads to renal failure. It may also be accompanied by extra-renal alterations, such as: sensorineural hearing loss, and ocular abnormalities. Dominant forms related to the X chromosome and caused by mutations in the locus COL4A5

  5. Contact lens fitting in a patient with Alport syndrome and posterior polymorphous corneal dystrophy: a case report

    Directory of Open Access Journals (Sweden)

    Juliana Maria da Silva Rosa

    2016-02-01

    Full Text Available ABSTRACT Alport Syndrome is a hereditary disease that is caused by a gene mutation and affects the production of collagen in basement membranes; this condition causes hemorrhagic nephritis associated with deafness and ocular changes. The X-linked form of this disease is the most common and mainly affects males. Typical ocular findings are dot-and-fleck retinopathy, anterior lenticonus, and posterior polymorphous corneal dystrophy. Some cases involving polymorphous corneal dystrophy and corneal ectasia have been previously described. Here we present a case report of a 33-year-old female with Alport syndrome, posterior polymorphous corneal dystrophy, and irregular astigmatism, whose visual acuity improved with a rigid gas permeable contact lens.

  6. Contact lens fitting in a patient with Alport syndrome and posterior polymorphous corneal dystrophy: a case report.

    Science.gov (United States)

    Rosa, Juliana Maria da Silva; Andrade Sobrinho, Marcelo Vicente de; Lipener, César

    2016-02-01

    Alport Syndrome is a hereditary disease that is caused by a gene mutation and affects the production of collagen in basement membranes; this condition causes hemorrhagic nephritis associated with deafness and ocular changes. The X-linked form of this disease is the most common and mainly affects males. Typical ocular findings are dot-and-fleck retinopathy, anterior lenticonus, and posterior polymorphous corneal dystrophy. Some cases involving polymorphous corneal dystrophy and corneal ectasia have been previously described. Here we present a case report of a 33-year-old female with Alport syndrome, posterior polymorphous corneal dystrophy, and irregular astigmatism, whose visual acuity improved with a rigid gas permeable contact lens. PMID:26840166

  7. Contact lens fitting in a patient with Alport syndrome and posterior polymorphous corneal dystrophy: a case report

    OpenAIRE

    Juliana Maria da Silva Rosa; Marcelo Vicente de Andrade Sobrinho; César Lipener

    2016-01-01

    ABSTRACT Alport Syndrome is a hereditary disease that is caused by a gene mutation and affects the production of collagen in basement membranes; this condition causes hemorrhagic nephritis associated with deafness and ocular changes. The X-linked form of this disease is the most common and mainly affects males. Typical ocular findings are dot-and-fleck retinopathy, anterior lenticonus, and posterior polymorphous corneal dystrophy. Some cases involving polymorphous corneal dystrophy and cornea...

  8. Alport syndrome: significance of gingival biopsy in the initial diagnosis and periodontal evaluation after renal transplantation

    Directory of Open Access Journals (Sweden)

    Hilal Uslu Toygar

    2009-12-01

    Full Text Available Alport Syndrome (AS is an important hereditary disorder affecting the glomerular basement membrane. Diagnosis of AS is based on the presence of hematuric nephropathy, renal failure, hearing loss, ocular abnormalities and changes in the glomerular basement membrane of the lamina densa. The aims of this case report were to show the changes in the gingival tissues in a patient with AS under therapy with cyclosporin-A after renal transplantation and to discuss the possible role of type IV collagen in gingival basal lamina as an alternative approach for the diagnosis of AS. A 20-year-old male patient with AS underwent periodontal therapy including a series of gingivectomy surgeries. Gingival samples obtained during the second surgery were examined histopathologically and by transmission electron microscopy for further pathological examination. Gingivectomy procedures have been performed every 6 months over the last 4 years. The excessive and fibrous gingival enlargements resulted in migration of the anterior teeth, but no alveolar bone loss occurred. This is the first report to demonstrate the possible changes in the gingival tissues caused by AS. It is suggested that gingival biopsy can be an initial diagnostic tool instead of renal or skin biopsies. Proper dental and periodontal care and regular visits to the dentist could provide limited gingival hyperplasia to patients with AS.

  9. A nonsense mutation in the COL4A5 collagen gene in a family with X-linked juvenile Alport syndrome

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Heiskari, N; Zhou, J; Jensen, U B; Tryggvason, K

    1995-01-01

    47 of the COL4A5 gene in a patient with a juvenile form of X-linked Alport syndrome with deafness. This two base deletion caused a shift in the reading frame and introduced a premature stop codon which resulted in an alpha 5(IV)-chain shortened by 202 residues and lacking almost the entire NC1 domain....... Prenatal diagnosis on chorionic villi tissue, obtained from one of the female carriers in the family, revealed a male fetus hemizygous for the mutated allele. A subsequent prenatal test in her next pregnancy revealed a normal male fetus. Prenatal diagnosis of Alport syndrome has not previously been...

  10. Dados clínicos e da audição em indivíduos com Síndrome de Alport Clinical data and hearing of individuals with Alport syndrome

    Directory of Open Access Journals (Sweden)

    Fatima Regina Abreu Alves

    2008-12-01

    Full Text Available A Síndrome de Alport (SA é uma desordem hereditária, caracterizada por nefropatia, muitas vezes, com perda auditiva sensorioneural e com defeitos oculares. OBJETIVO: Analisar os dados clínicos e da audição em indivíduos com SA, com ênfase na correlação entre alteração renal e perda auditiva (PA. FORMA DE ESTUDO: clínico prospectivo com coorte transversal. CASUÍSTICA E MÉTODO: 37 indivíduos realizaram avaliação otorrinolaringológica e testes audiológicos. Foram considerados para a análise estatística da PA os resultados das audiometrias de tons puros. RESULTADOS: Nos 28 indivíduos que apresentavam alterações clínicas foram encontrados 46,4% de DLX e 53,6% de AD. A PA ocorreu em 46,1% dos avaliados. 12 pacientes tinham PA no exame audiométrico 11,5%, leve e 34,6%, moderada. Comparados os familiares normais aos que tinham alteração renal, todos os que apresentavam PA mostravam comprometimento renal. Em 30,8% a configuração era descendente suave em agudos e em 11,5% era plana. CONCLUSÕES: A distribuição dos padrões de herança não coincide com o descrito na literatura. A PA é um achado extra-renal freqüente. Existe associação entre acometimento renal e PA (p= 0,009. As configurações mais freqüentes foram: descendente suave em agudos e plana. Não há associação entre a PA e a idade. Não existe correlação entre PA e sexo neste grupo.Alport Syndrome (AS is a hereditary disease, characterized by nephropathy, often times with sensorineural hearing loss and ocular defects. AIM: to analyze the clinical and hearing information from individuals with AS, more specifically the correlation between renal disorder and hearing loss (HL. STUDY DESIGN: clinical prospective with cross-sectional cohort. MATERIALS AND METHODS: 37 individuals underwent otorhinolaryngological evaluation and were submitted to audiologic tests. For HL statistical analysis we considered only the results from the pure tone audiometries

  11. [Alport syndrom (author's transl)].

    Science.gov (United States)

    Schönenberg, H; Marenberg, H G

    1977-04-01

    A deaf-and-dumb patient died at the age of ten of failure of the kidneys. An uncle of the boy died at the age of 42, an aunt at the age of 16 years, both of atrophic kidneys. The mother of the proband is suffering from hard hearing on one side and recurrent episodes of pyuria. Repeated examinations in two aunts revealed slight pyuria resp. erythruria. Contrary to most reports affected members of the family showed pyuria rather than haematuria. A special inheritance could not be proved. PMID:323696

  12. Quaternary epitopes of α345(IV) collagen initiate Alport post-transplant anti-GBM nephritis

    DEFF Research Database (Denmark)

    Olaru, Florina; Luo, Wentian; Wang, Xu-Ping; Ge, Linna; Hertz, Jens Michael; Kashtan, Clifford E; Sado, Yoshikazu; Segal, Yoav; Hudson, Billy G; Borza, Dorin-Bogdan

    2013-01-01

    Alport post-transplant nephritis (APTN) is an aggressive form of anti-glomerular basement membrane disease that targets the allograft in transplanted patients with X-linked Alport syndrome. Alloantibodies develop against the NC1 domain of α5(IV) collagen, which occurs in normal kidneys, including...

  13. Podocyturia: A Clue for the Rational Use of Amiloride in Alport Renal Disease.

    Science.gov (United States)

    Trimarchi, H; Canzonieri, R; Muryan, A; Schiel, A; Araoz, A; Paulero, M; Andrews, J; Rengel, T; Forrester, M; Lombi, F; Pomeranz, V; Iriarte, R; Zotta, E

    2016-01-01

    No specific or efficient treatment exists for Alport syndrome, an X-linked hereditary disease caused by mutations in collagen type IV, a crucial component of the glomerular basement membrane. Kidney failure is usually a major complication of the disease, and patients require renal replacement therapy early in life. Microhematuria and subsequently proteinuria are hallmarks of kidney involvement, which are due to primary basement membrane alterations that mainly cause endothelial thrombosis and podocyte contraction and ulterior irreversible detachment. Commonly drug-based approaches include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, which are employed to reduce proteinuria and thus retard kidney disease progression and cardiovascular morbidity and mortality. However, as any hereditary disease, it is expressed as early as in the intrauterine life, and usually an index case is helpful to detect family-related cases. As no specific treatment exists, pathophysiologically based approaches are useful. The present case illustrates the reduction rate of urinary podocyte loss and proteinuria after amiloride administration and suggests the molecular pathways involved in Alport renal disease. Finally, podocyturia rather than proteinuria should be considered as an earlier biomarker of kidney involvement and disease progression in Alport disease. PMID:26942026

  14. Podocyturia: A Clue for the Rational Use of Amiloride in Alport Renal Disease

    Directory of Open Access Journals (Sweden)

    H. Trimarchi

    2016-01-01

    Full Text Available No specific or efficient treatment exists for Alport syndrome, an X-linked hereditary disease caused by mutations in collagen type IV, a crucial component of the glomerular basement membrane. Kidney failure is usually a major complication of the disease, and patients require renal replacement therapy early in life. Microhematuria and subsequently proteinuria are hallmarks of kidney involvement, which are due to primary basement membrane alterations that mainly cause endothelial thrombosis and podocyte contraction and ulterior irreversible detachment. Commonly drug-based approaches include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, which are employed to reduce proteinuria and thus retard kidney disease progression and cardiovascular morbidity and mortality. However, as any hereditary disease, it is expressed as early as in the intrauterine life, and usually an index case is helpful to detect family-related cases. As no specific treatment exists, pathophysiologically based approaches are useful. The present case illustrates the reduction rate of urinary podocyte loss and proteinuria after amiloride administration and suggests the molecular pathways involved in Alport renal disease. Finally, podocyturia rather than proteinuria should be considered as an earlier biomarker of kidney involvement and disease progression in Alport disease.

  15. Targeted exome sequencing integrated with clinicopathological information reveals novel and rare mutations in atypical, suspected and unknown cases of Alport syndrome or proteinuria.

    Directory of Open Access Journals (Sweden)

    Rajshekhar Chatterjee

    Full Text Available We applied customized targeted next-generation exome sequencing (NGS to determine if mutations in genes associated with renal malformations, Alport syndrome (AS or nephrotic syndrome are a potential cause of renal abnormalities in patients with equivocal or atypical presentation. We first sequenced 4,041 exons representing 292 kidney disease genes in a Caucasian woman with a history of congenital vesicoureteral reflux (VUR, recurrent urinary tract infections and hydronephrosis who presented with nephrotic range proteinuria at the age of 45. Her biopsy was remarkable for focal segmental glomerulosclerosis (FSGS, a potential complication of longstanding VUR. She had no family history of renal disease. Her proteinuria improved initially, however, several years later she presented with worsening proteinuria and microhematuria. NGS analysis revealed two deleterious COL4A3 mutations, one novel and the other previously reported in AS, and a novel deleterious SALL2 mutation, a gene linked to renal malformations. Pedigree analysis confirmed that COL4A3 mutations were nonallelic and compound heterozygous. The genomic results in conjunction with subsequent abnormal electron microscopy, Collagen IV minor chain immunohistochemistry and progressive sensorineural hearing loss confirmed AS. We then modified our NGS approach to enable more efficient discovery of variants associated with AS or a subset of FSGS by multiplexing targeted exome sequencing of 19 genes associated with AS or FSGS in 14 patients. Using this approach, we found novel or known COL4A3 or COL4A5 mutations in a subset of patients with clinically diagnosed or suspected AS, APOL1 variants associated with FSGS in African Americans and novel mutations in genes associated with nephrotic syndrome. These studies demonstrate the successful application of targeted capture-based exome sequencing to simultaneously evaluate genetic variations in many genes in patients with complex renal phenotypes and

  16. Genetics Home Reference: Alport syndrome

    Science.gov (United States)

    ... for making one component of a protein called type IV collagen. This protein plays an important role in the ... in these genes result in abnormalities of the type IV collagen in glomeruli, which prevents the kidneys from properly ...

  17. Podocyturia: A Clue for the Rational Use of Amiloride in Alport Renal Disease

    OpenAIRE

    H. Trimarchi; R. Canzonieri; Muryan, A.; Schiel, A.; Araoz, A.; Paulero, M.; Andrews, J; Rengel, T.; Forrester, M.; F. Lombi; V. Pomeranz; Iriarte, R.; Zotta, E.

    2016-01-01

    No specific or efficient treatment exists for Alport syndrome, an X-linked hereditary disease caused by mutations in collagen type IV, a crucial component of the glomerular basement membrane. Kidney failure is usually a major complication of the disease, and patients require renal replacement therapy early in life. Microhematuria and subsequently proteinuria are hallmarks of kidney involvement, which are due to primary basement membrane alterations that mainly cause endothelial thrombosis and...

  18. Progression of Alport Kidney Disease in Col4a3 Knock Out Mice Is Independent of Sex or Macrophage Depletion by Clodronate Treatment.

    Directory of Open Access Journals (Sweden)

    Munkyung Kim

    Full Text Available Alport syndrome is a genetic disease of collagen IV (α3, 4, 5 resulting in renal failure. This study was designed to investigate sex-phenotype correlations and evaluate the contribution of macrophage infiltration to disease progression using Col4a3 knock out (Col4a3KO mice, an established genetic model of autosomal recessive Alport syndrome. No sex differences in the evolution of body mass loss, renal pathology, biomarkers of tubular damage KIM-1 and NGAL, or deterioration of kidney function were observed during the life span of Col4a3KO mice. These findings confirm that, similar to human autosomal recessive Alport syndrome, female and male Col4a3KO mice develop renal failure at the same age and with similar severity. The specific contribution of macrophage infiltration to Alport disease, one of the prominent features of the disease in human and Col4a3KO mice, remains unknown. This study shows that depletion of kidney macrophages in Col4a3KO male mice by administration of clodronate liposomes, prior to clinical onset of disease and throughout the study period, does not protect the mice from renal failure and interstitial fibrosis, nor delay disease progression. These results suggest that therapy targeting macrophage recruitment to kidney is unlikely to be effective as treatment of Alport syndrome.

  19. 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...

  20. Nephritogenic antigen determinants in epidermal and renal basement membranes of kindreds with Alport-type familial nephritis.

    OpenAIRE

    Kashtan, C; Fish, A. J.; Kleppel, M; Yoshioka, K; Michael, A. F.

    1986-01-01

    We probed epidermal basement membranes (EBM) of acid-urea denatured skin from members of kindreds with Alport-type familial nephritis (FN) for the presence of antigens reactive with Goodpasture sera (GPS) and serum (FNS) from an Alport patient who developed anti-glomerular basement membrane (GBM) nephritis in a renal allograft. By immunoblotting, GPS reacted primarily with the 28,000 molecular weight (mol wt) monomer but also the 24,000 mol wt and 26,000 mol wt monomers of the noncollagenous ...

  1. Molecular diagnosis of Down ' s syndrome

    Institute of Scientific and Technical Information of China (English)

    王树玉; 贾婵维; 任国庆; 马延敏; 吕巍; 丁锋; 韩健

    2003-01-01

    Objective To establish a new diagnostic method for Down ' s syndrome using polymerase chain reaction (PCR).Methods DNA extracted from five healthy individuals and five Down ' s syndrome patients was amplified in six specific tetranucleotide repeat loci on chromosome 21 using PCR. An accurate diagnosis was made by analyzing allelic distribution at each locus. Results All Down ' s syndrome patients were identified as having at least two loci with three alleles, while none of the healthy individuals had three alleles. In addition, when two alleles were identified for a particular locus in the Down ' s syndrome samples, it was more likely that the intensity ratio between the two alleles was close to 2∶ 1.Conclusion The molecular method can provide a fast, accurate, and economical alternation for the traditional cytogenetic diagnostic method for Down ' s syndrome.

  2. Quaternary epitopes of α345(IV) collagen initiate Alport post-transplant anti-GBM nephritis.

    Science.gov (United States)

    Olaru, Florina; Luo, Wentian; Wang, Xu-Ping; Ge, Linna; Hertz, Jens Michael; Kashtan, Clifford E; Sado, Yoshikazu; Segal, Yoav; Hudson, Billy G; Borza, Dorin-Bogdan

    2013-05-01

    Alport post-transplant nephritis (APTN) is an aggressive form of anti-glomerular basement membrane disease that targets the allograft in transplanted patients with X-linked Alport syndrome. Alloantibodies develop against the NC1 domain of α5(IV) collagen, which occurs in normal kidneys, including renal allografts, forming distinct α345(IV) and α1256(IV) networks. Here, we studied the roles of these networks as antigens inciting alloimmunity and as targets of nephritogenic alloantibodies in APTN. We found that patients with APTN, but not those without nephritis, produce two kinds of alloantibodies against allogeneic collagen IV. Some alloantibodies targeted alloepitopes within α5NC1 monomers, shared by α345NC1 and α1256NC1 hexamers. Other alloantibodies specifically targeted alloepitopes that depended on the quaternary structure of α345NC1 hexamers. In Col4a5-null mice, immunization with native forms of allogeneic collagen IV exclusively elicited antibodies to quaternary α345NC1 alloepitopes, whereas alloimmunogens lacking native quaternary structure elicited antibodies to shared α5NC1 alloepitopes. These results imply that quaternary epitopes within α345NC1 hexamers may initiate alloimmune responses after transplant in X-linked Alport patients. Thus, α345NC1 hexamers are the culprit alloantigen and primary target of all alloantibodies mediating APTN, whereas α1256NC1 hexamers become secondary targets of anti-α5NC1 alloantibodies. Reliable detection of alloantibodies by immunoassays using α345NC1 hexamers may improve outcomes by facilitating early, accurate diagnosis. PMID:23620401

  3. Molecular diagnosis of Turner's syndrome.

    OpenAIRE

    Gicquel, C.; Cabrol, S; Schneid, H.; Girard, F; Le Bouc, Y

    1992-01-01

    Turner's syndrome is a common disorder which occurs in around 1/3000 live births in girls. Diagnostic use of polymorphic DNA markers for the X chromosome could help to reduce the number of time consuming karyotype analyses needed. The M27 beta probe maps on the X chromosome to Xcen-Xp11-22 and in 83% of female subjects detects heterozygosity with multiallelic polymorphism. In Southern blotting, a single X chromosome yields a single hybridisation band. In this study, genomic DNA was extracted ...

  4. Turcot syndrome confirmed with molecular analysis.

    Science.gov (United States)

    Lebrun, C; Olschwang, S; Jeannin, S; Vandenbos, F; Sobol, H; Frenay, M

    2007-04-01

    Turcot syndrome is clinically characterized by the occurrence of primary brain tumor and colorectal tumor and has, in previous reports, been shown associated with germline mutations in the genes APC, MLH1, MHS6, and PMS2. To date, only few families have been documented by molecular analysis. We report two new families with Turcot syndrome to illustrate and review its characteristics and facilitate diagnosis. Molecular analysis revealed two germline mutations, one in the MLH1 gene and one in MSH2. The latter has never been describe in the literature. Personal and familial relevant anamnestic data from patients with glioma might aid in the diagnosis of genetic disorders. The subsequent molecular characterization may contribute to the appropriate care of affected patients and asymptomatic gene carriers. PMID:17389002

  5. Neuroligins Provide Molecular Links Between Syndromic and Non-Syndromic Autism

    OpenAIRE

    Singh, Sandeep K.; Eroglu, Cagla

    2013-01-01

    Autism is a common and heritable neuropsychiatric disorder that can be categorized into two types: syndromic and non-syndromic, the former of which are associated with other neurological disorders or syndromes. Molecular and functional links between syndromic and non-syndromic autism genes were lacking until studies aimed at understanding role of trans-synaptic adhesion molecule neuroligin, which is associated with non-syndromic autism, provided important connections. Here, we integrate data ...

  6. Kabuki syndrome: clinical and molecular characteristics.

    Science.gov (United States)

    Cheon, Chong-Kun; Ko, Jung Min

    2015-09-01

    Kabuki syndrome (KS) is a rare syndrome characterized by multiple congenital anomalies and mental retardation. Other characteristics include a peculiar facial gestalt, short stature, skeletal and visceral abnormalities, cardiac anomalies, and immunological defects. Whole exome sequencing has uncovered the genetic basis of KS. Prior to 2013, there was no molecular genetic information about KS in Korean patients. More recently, direct Sanger sequencing and exome sequencing revealed KMT2D variants in 11 Korean patients and a KDM6A variant in one Korean patient. The high detection rate of KMT2D and KDM6A mutations (92.3%) is expected owing to the strict criteria used to establish a clinical diagnosis. Increased awareness and understanding of KS among clinicians is important for diagnosis and management of KS and for primary care of KS patients. Because mutation detection rates rely on the accuracy of the clinical diagnosis and the inclusion or exclusion of atypical cases, recognition of KS will facilitate the identification of novel mutations. A brief review of KS is provided, highlighting the clinical and genetic characteristics of patients with KS. PMID:26512256

  7. Molecular cytogenetic diagnosis of Williams syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Hirota, Hamao; Matsuoka, Rumiko; Kimura, Misa [Heart Institute of Japan, Tokyo (Japan)] [and others

    1996-08-23

    Williams syndrome (WS) is characterized by distinct facial changes, growth deficiency, mental retardation, and congenital heart defect (particularly supravalvular aortic stenosis), associated at times with infantile hypercalcemia. Molecular genetic studies have indicated that hemizygosity at the elastin locus (7q11.23) causes WS. The purpose of this study was to confirm that this regional deletion, involving the elastin locus, is the cause of WS in Japan, and to clarify the correlation between the phenotype and the elastin locus. Thirty-two patients with WS and thirty of their relatives were examined by fluorescent in situ hybridization (FISH), using the WS chromosome region (WSCR) probe. All patients had cardiovascular disease (100%), 30 had typical WS facial changes (94%), 31 had mental retardation or developmental delay (97%), 16 were small-for-date at birth (50%), 14 had short stature (44%), and 13 had dental anomalies (41%). No relatives showed any manifestation of WS. Hemizygosity for a region of 7q11.23, involving the elastin locus, was found in all WS patients, but was not found in the 30 relatives. 22 refs., 4 figs., 1 tab.

  8. Genes and Syndromic Hearing Loss.

    Science.gov (United States)

    Keats, Bronya J. B.

    2002-01-01

    This article provides a description of the human genome and patterns of inheritance and discusses genes that are associated with some of the syndromes for which hearing loss is a common finding, including: Waardenburg, Stickler, Jervell and Lange-Neilsen, Usher, Alport, mitochondrial encephalomyopathy, and sensorineural hearing loss. (Contains…

  9. Rett syndrome molecular diagnosis and implications in genetic counseling

    Directory of Open Access Journals (Sweden)

    Noruzinia M

    2007-01-01

    Full Text Available Rett syndrome is a rare genetic X-linked dominant disorder. This syndrome is the most frequent cause of mental retardation in girls. In the classical form of the disease, the presenting signs and the course of development are characteristic. However clinical diagnosis can be very difficult when the expression is not in the classical form. Mutations in MeCP2 are responsible for 80% of cases. When MeCP2 mutation is found in an index case, genetic counseling is similar to that in other X-linked dominant genetic diseases. However, mutations in this gene can cause a spectrum of atypical forms. On the other hand, other genetic conditions like translocations, sex chromosome numerical anomalies, and mutations in other genes can complicate genetic counseling in this syndrome. We present the first case of molecular diagnosis of Rett syndrome in Iran and discuss the recent developments in its genetic counseling.

  10. The molecular mechanisms between metabolic syndrome and breast cancer.

    Science.gov (United States)

    Chen, Yi; Wen, Ya-Yuan; Li, Zhi-Rong; Luo, Dong-Lin; Zhang, Xiao-Hua

    2016-03-18

    Metabolic syndrome, which is extremely common in developed and some developing countries, is a clustering of at least three of five of the following medical conditions: abdominal obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides, and low high-density lipoprotein levels. It has been proved that there is a strong association between metabolic syndrome and breast cancer. Metabolic syndrome could increase the risk of breast cancer and influence the prognosis of the breast cancer patients. Some characteristic of metabolic syndrome such as obesity and lack of physical exercise are all risk factors for developing breast cancer. The metabolic syndrome mainly include obesity, type 2 diabetes, hypercholesterolemia and nonalcoholic fatty liver disease, and each of them impacts the risk of breast cancer and the prognosis of the breast cancer patients in different ways. In this Review, we focus on recently uncovered aspects of the immunological and molecular mechanisms that are responsible for the development of this highly prevalent and serious disease. These studies bring new insight into the complex associations between metabolic syndrome and breast cancer and have led to the development of novel therapeutic strategies that might enable a personalized approach in the management of this disease. PMID:26891869

  11. Insights into the molecular genetics of Kabuki syndrome

    Directory of Open Access Journals (Sweden)

    Adam MP

    2015-02-01

    Full Text Available Margaret P Adam Department of Pediatrics, Division of Genetic Medicine, University of Washington School of Medicine, Seattle, WA, USA Abstract: Kabuki syndrome (KS is a well-recognized multiple congenital anomaly/intellectual disability syndrome characterized by distinctive facial features, congenital heart defects, skeletal anomalies, persistent fingertip pads, postnatal growth retardation, and cognitive impairment to varying degrees. To date, mutations or deletions in two genes (KMT2D and KDM6A have been identified to cause the majority of cases of KS. Both genes are involved in histone modification and epigenetic regulation of gene expression in early embryogenesis. In this report, we review the clinical features and management of patients with KS, explore the proposed protein interactions and the molecular pathway that may lead to features of KS, and discuss how knowledge of the molecular mechanisms has the potential to inform further disease gene discovery and targeted treatment of the condition. Keywords: Kabuki syndrome, Kabuki make-up syndrome, KMT2D, KDM6A, histone modification

  12. Identification of noncollagenous sites encoding specific interactions and quaternary assembly of alpha 3 alpha 4 alpha 5(IV) collagen: implications for Alport gene therapy.

    Science.gov (United States)

    Kang, Jeong Suk; Colon, Selene; Hellmark, Thomas; Sado, Yoshikazu; Hudson, Billy G; Borza, Dorin-Bogdan

    2008-12-12

    Defective assembly of alpha 3 alpha 4 alpha 5(IV) collagen in the glomerular basement membrane causes Alport syndrome, a hereditary glomerulonephritis progressing to end-stage kidney failure. Assembly of collagen IV chains into heterotrimeric molecules and networks is driven by their noncollagenous (NC1) domains, but the sites encoding the specificity of these interactions are not known. To identify the sites directing quaternary assembly of alpha 3 alpha 4 alpha 5(IV) collagen, correctly folded NC1 chimeras were produced, and their interactions with other NC1 monomers were evaluated. All alpha1/alpha 5 chimeras containing alpha 5 NC1 residues 188-227 replicated the ability of alpha 5 NC1 to bind to alpha3NC1 and co-assemble into NC1 hexamers. Conversely, substitution of alpha 5 NC1 residues 188-227 by alpha1NC1 abolished these quaternary interactions. The amino-terminal 58 residues of alpha3NC1 encoded binding to alpha 5 NC1, but this interaction was not sufficient for hexamer co-assembly. Because alpha 5 NC1 residues 188-227 are necessary and sufficient for assembly into alpha 3 alpha 4 alpha 5 NC1 hexamers, whereas the immunodominant alloantigenic sites of alpha 5 NC1 do not encode specific quaternary interactions, the findings provide a basis for the rational design of less immunogenic alpha 5(IV) collagen constructs for the gene therapy of X-linked Alport patients. PMID:18930919

  13. Clinical and molecular phenotype of Aicardi-Goutieres syndrome

    OpenAIRE

    Rice, Gillian; Patrick, Teresa; Parmar, Rekha; Taylor, Claire F.; Aeby, Alec; Aicardi, Jean; Artuch, Rafael; Montalto, Simon Attard; Bacino, Carlos A.; Barroso, Bruno; Baxter, Peter; Benko, Willam S; Bergmann, Carsten; Bertini, Enrico; Biancheri, Roberta

    2007-01-01

    Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3'-->5' exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNA...

  14. Cytogenetic and molecular findings in patients with Turner's syndrome stigmata.

    OpenAIRE

    Kuznetzova, T; Baranov, A; Schwed, N; Ivaschenko, T; Malet, P; Giollant, M.; Savitsky, G A; Baranov, V.

    1995-01-01

    Cytogenetic and DNA analysis in 12 people with stigmata of Turner's syndrome was carried out. Cytogenetic analysis of these patients showed two subjects with 46,X, i(Xq) karyotypes, one with 45,X/46,X, i(Xq), one with 46,X,t(X;Y), and eight with 45,X/46,X,mar. Molecular analysis of DNA samples was performed in nine out of 12 patients with marker chromosomes. PCR analysis with oligoprimers specific for SRY, DYZ1, or DYZ3 loci identified Y chromosome material in five patients in the latter grou...

  15. Underlying molecular and cellular mechanisms in childhood irritable bowel syndrome.

    Science.gov (United States)

    Chumpitazi, Bruno P; Shulman, Robert J

    2016-12-01

    Irritable bowel syndrome (IBS) affects a large number of children throughout the world. The symptom expression of IBS is heterogeneous, and several factors which may be interrelated within the IBS biopsychosocial model play a role. These factors include visceral hyperalgesia, intestinal permeability, gut microbiota, psychosocial distress, gut inflammation, bile acids, food intolerance, colonic bacterial fermentation, and genetics. The molecular and cellular mechanisms of these factors are being actively investigated. In this mini-review, we present updates of these mechanisms and, where possible, relate the findings to childhood IBS. Mechanistic elucidation may lead to the identification of biomarkers as well as personalized childhood IBS therapies. PMID:26883355

  16. Laminin α2-mediated focal adhesion kinase activation triggers Alport glomerular pathogenesis.

    Directory of Open Access Journals (Sweden)

    Duane Delimont

    Full Text Available It has been known for some time that laminins containing α1 and α2 chains, which are normally restricted to the mesangial matrix, accumulate in the glomerular basement membranes (GBM of Alport mice, dogs, and humans. We show that laminins containing the α2 chain, but not those containing the α1 chain activates focal adhesion kinase (FAK on glomerular podocytes in vitro and in vivo. CD151-null mice, which have weakened podocyte adhesion to the GBM rendering these mice more susceptible to biomechanical strain in the glomerulus, also show progressive accumulation of α2 laminins in the GBM, and podocyte FAK activation. Analysis of glomerular mRNA from both models demonstrates significant induction of MMP-9, MMP-10, MMP-12, MMPs linked to GBM destruction in Alport disease models, as well as the pro-inflammatory cytokine IL-6. SiRNA knockdown of FAK in cultured podocytes significantly reduced expression of MMP-9, MMP-10 and IL-6, but not MMP-12. Treatment of Alport mice with TAE226, a small molecule inhibitor of FAK activation, ameliorated fibrosis and glomerulosclerosis, significantly reduced proteinuria and blood urea nitrogen levels, and partially restored GBM ultrastructure. Glomerular expression of MMP-9, MMP-10 and MMP-12 mRNAs was significantly reduced in TAE226 treated animals. Collectively, this work identifies laminin α2-mediated FAK activation in podocytes as an important early event in Alport glomerular pathogenesis and suggests that FAK inhibitors, if safe formulations can be developed, might be employed as a novel therapeutic approach for treating Alport renal disease in its early stages.

  17. Autoepitopes and alloepitopes of type IV collagen: role in the molecular pathogenesis of anti-GBM antibody glomerulonephritis.

    Science.gov (United States)

    Borza, Dorin-Bogdan

    2007-01-01

    Anti-glomerular basement membrane (anti-GBM) antibodies elicited by autoimmune or alloimmune mechanisms are associated with aggressive forms of rapid progressive glomerulonephritis. Pathogenic anti-GBM autoantibodies and alloantibodies target the noncollagenous (NC1) domains of the alpha3alpha4alpha5(IV) collagen, a major GBM component. In autoimmune anti-GBM glomerulonephritis, a breakdown of immune self-tolerance leads to the activation of autoreactive B and T cells recognizing epitopes within the alpha3NC1 subunit. In the GBM, the conformational epitopes targeted by anti-GBM autoantibodies are structurally sequestered within the alpha3alpha4alpha5NC1 hexamer complex formed upon assembly of collagen IV chains into trimeric molecules and networks. Autoantibodies selectively bind to and dissociate a subset of alpha3alpha4alpha5NC1 hexamers composed of monomer subunits, whereas hexamers containing NC1 dimer subunits are resistant to dissociation by autoantibodies. The crypticity of alpha3NC1 autoepitopes suggests that self-tolerance to alpha3(IV) collagen is broken by structural alterations of the native alpha3alpha4alpha5NC1 hexamer that unmask normally sequestered epitopes, triggering an autoimmune reaction. Post-transplant anti-GBM nephritis in the renal allograft of transplanted Alport patients is mediated by an alloimmune reaction to the NC1 domains of alpha3alpha4alpha5(IV) collagen, present in the allograft GBM but absent from Alport basement membranes. Alloantibodies from patients with autosomal-recessive Alport syndrome predominantly bind to the alpha3NC1 domain, whereas alloantibodies from X-linked Alport patients target preferentially, though not exclusively, epitopes within the alpha5NC1 subunit. The accessibility of the alloantigenic sites within the alpha3alpha4alpha5NC1 hexamers, contrasting with the crypticity of autoantigenic sites, suggest that different molecular forms of alpha3alpha4alpha5(IV) collagen initiate the immunopathogenic responses in

  18. Fishing the molecular bases of Treacher Collins syndrome.

    Directory of Open Access Journals (Sweden)

    Andrea M J Weiner

    Full Text Available Treacher Collins syndrome (TCS is an autosomal dominant disorder of craniofacial development, and mutations in the TCOF1 gene are responsible for over 90% of TCS cases. The knowledge about the molecular mechanisms responsible for this syndrome is relatively scant, probably due to the difficulty of reproducing the pathology in experimental animals. Zebrafish is an emerging model for human disease studies, and we therefore assessed it as a model for studying TCS. We identified in silico the putative zebrafish TCOF1 ortholog and cloned the corresponding cDNA. The derived polypeptide shares the main structural domains found in mammals and amphibians. Tcof1 expression is restricted to the anterior-most regions of zebrafish developing embryos, similar to what happens in mouse embryos. Tcof1 loss-of-function resulted in fish showing phenotypes similar to those observed in TCS patients, and enabled a further characterization of the mechanisms underlying craniofacial malformation. Besides, we initiated the identification of potential molecular targets of treacle in zebrafish. We found that Tcof1 loss-of-function led to a decrease in the expression of cellular proliferation and craniofacial development. Together, results presented here strongly suggest that it is possible to achieve fish with TCS-like phenotype by knocking down the expression of the TCOF1 ortholog in zebrafish. This experimental condition may facilitate the study of the disease etiology during embryonic development.

  19. Serrated polyposis syndrome: Molecular, pathological and clinical aspects

    Institute of Scientific and Technical Information of China (English)

    Carla Guarinos; Cristina Sánchez-Fortún; María Rodríguez-Soler; Cristina Alenda; Artemio Payá; Rodrigo Jover

    2012-01-01

    Hyperplastic polyps have traditionally been considered not to have malignant potential.New pathological classification of serrated polyps and recent discoveries about the serrated pathway of carcinogenesis have revolutionized the concepts and revitalized the research in this area.Until recently,it has been thought that most colorectal cancers arise from conventional adenomas via the traditional tumor suppressor pathway initiated by a mutation of the APC gene,but it has been found that this pathway accounts for only approximately 70%-80%of colorectal cancer (CRC) cases.The majority of the remaining colorectal cancer cases follow an alternative pathway leading to CpG island methylator phenotype carcinoma with BRAF mutation and with or without microsatellite instability.The mechanism of carcinomas arising from this alternative pathway seems to begin with an activating mutation of the BRAF oncogene.Serrated polyposis syndrome is a relatively rare condition characterized by multiple and/or large serrated polyps of the colon.Clinical characteristics,etiology and relationship of serrated polyposis syndrome to CRC have not been clarified yet.Patients with this syndrome show a high risk of CRC and both sporadic and hereditary cases have been described.Clinical criteria have been used for diagnosis and frequent colonoscopy surveillance should be performed in order to prevent colorectal cancer.In this review,we try to gather new insights into the molecular pathogenesis of serrated polyps in order to understand their possible clinical implications and to make an approach to the management of this syndrome.

  20. The alloantigenic sites of alpha3alpha4alpha5(IV) collagen: pathogenic X-linked alport alloantibodies target two accessible conformational epitopes in the alpha5NC1 domain.

    Science.gov (United States)

    Kang, Jeong Suk; Kashtan, Clifford E; Turner, A Neil; Heidet, Laurence; Hudson, Billy G; Borza, Dorin-Bogdan

    2007-04-01

    Anti-glomerular basement membrane (GBM) antibody nephritis is caused by an autoimmune or alloimmune reaction to the NC1 domains of alpha3alpha4alpha5(IV) collagen. Some patients with X-linked Alport syndrome (XLAS) develop post-transplant nephritis mediated by pathogenic anti-GBM alloantibodies to collagen IV chains present in the renal allograft but absent from the tissues of the patient. In this work, the epitopes targeted by alloantibodies from these patients were identified and characterized. All XLAS alloantibodies recognized conformational epitopes in the NC1 domain of alpha5(IV) collagen, which were mapped using chimeric alpha1/alpha5 NC1 domains expressed in mammalian cells. Allograft-eluted alloantibodies mainly targeted two conformational alloepitopes mapping to alpha5NC1 residues 1-45 and 114-168. These regions also encompassed the major epitopes of circulating XLAS alloantibodies, which in some patients additionally targeted alpha5NC1 residues 169-229. Both kidney-eluted and circulating alloantibodies to alpha5NC1 distinctively targeted epitopes accessible in the alpha3alpha4alpha5NC1 hexamers of human GBM, unlike anti-GBM autoantibodies, which targeted sequestered alpha3NC1 epitopes. The results identify two immunodominant alpha5NC1 epitopes as major alloantigenic sites of alpha3alpha4alpha5(IV) collagen specifically implicated in the pathogenesis of post-transplant nephritis in XLAS patients. The contrast between the accessibility of these alloepitopes and the crypticity of autoepitopes indicates that distinct molecular forms of antigen may initiate the immunopathogenic processes in the two forms of anti-GBM disease. PMID:17293596

  1. Molecular analysis of fragile X syndrome in Antalya Province

    Directory of Open Access Journals (Sweden)

    Bilgen T

    2005-04-01

    Full Text Available Background: Detection of the (CGGn repeats in the FMR1 gene that cause the fragile X syndrome (FXS, has become a milestone for phenotype-genotype correlation in FXS. Aims: To screen the FMR1 gene CGG repeats in index cases with FXS and their family members in the Antalya Province. Setting and design: This study was prospectively conducted between January 200and March 2005 in Department of Medical Biology and Genetics, Faculty of Medicine, Akdeniz University, Antalya. Materials and Methods: A series of 132 cases from three hospitals in Antalya Province were studied. All cases were molecularly screened using non-radioactive Expand Long PCR method that was confirmed by Southern blotting. Results: Seventeen out of 132 cases were found to have a full mutation, including three that were mosaic for premutations/full mutations. Of the 132 cases, eight were found to have the premutation size of the CGG repeats. The remaining 107 cases were identified as normal. Conclusions: Due to premature ovarian failure and Fragile X premutation Tremor/Ataxia Syndrome related with the premutation, the detection of the premutation will provide valuable information both for clinical follow-up and genetic counseling. In conclusion, our data suggest that expansion of CGG repeats in the FMR1 gene can be analyzed by Expand Long PCR, an efficient and non-radioactive method that can be used to monitor the expansion of premutation to full mutation, which would eventually lead to reduce the FXS prevalence.

  2. [Molecular Mimicry and Guillain-Barré Syndrome].

    Science.gov (United States)

    Yuki, Nobuhiro

    2015-11-01

    One-thirds of patients develop Guillain-Barré syndrome subsequent to Campylobacter jejuni enteritis. Molecular mimicry exists between C. jejuni lipo-oligosaccharides and human peripheral nerve gangliosides GM1 and GD1a. IgG antibodies against GM1 or GD1a are produced in one out of 5,000 patients with C. jejuni enteritis. The autoantibodies bind to gangliosides at the nodes of Ranvier in the peripheral motor nerves and activate complement in situ. This is followed by the disappearance of the voltage-gated sodium channel clusters at the nodes and disruption of axo-glial junctions at the paranodes. This results in the development of motor nerve conduction failure and muscle weakness in the four limbs. PMID:26560949

  3. Anti-microRNA-21 oligonucleotides prevent Alport nephropathy progression by stimulating metabolic pathways.

    Science.gov (United States)

    Gomez, Ivan G; MacKenna, Deidre A; Johnson, Bryce G; Kaimal, Vivek; Roach, Allie M; Ren, Shuyu; Nakagawa, Naoki; Xin, Cuiyan; Newitt, Rick; Pandya, Shweta; Xia, Tai-He; Liu, Xueqing; Borza, Dorin-Bogdan; Grafals, Monica; Shankland, Stuart J; Himmelfarb, Jonathan; Portilla, Didier; Liu, Shiguang; Chau, B Nelson; Duffield, Jeremy S

    2015-01-01

    MicroRNA-21 (miR-21) contributes to the pathogenesis of fibrogenic diseases in multiple organs, including the kidneys, potentially by silencing metabolic pathways that are critical for cellular ATP generation, ROS production, and inflammatory signaling. Here, we developed highly specific oligonucleotides that distribute to the kidney and inhibit miR-21 function when administered subcutaneously and evaluated the therapeutic potential of these anti-miR-21 oligonucleotides in chronic kidney disease. In a murine model of Alport nephropathy, miR-21 silencing did not produce any adverse effects and resulted in substantially milder kidney disease, with minimal albuminuria and dysfunction, compared with vehicle-treated mice. miR-21 silencing dramatically improved survival of Alport mice and reduced histological end points, including glomerulosclerosis, interstitial fibrosis, tubular injury, and inflammation. Anti-miR-21 enhanced PPARα/retinoid X receptor (PPARα/RXR) activity and downstream signaling pathways in glomerular, tubular, and interstitial cells. Moreover, miR-21 silencing enhanced mitochondrial function, which reduced mitochondrial ROS production and thus preserved tubular functions. Inhibition of miR-21 was protective against TGF-β-induced fibrogenesis and inflammation in glomerular and interstitial cells, likely as the result of enhanced PPARα/RXR activity and improved mitochondrial function. Together, these results demonstrate that inhibition of miR-21 represents a potential therapeutic strategy for chronic kidney diseases including Alport nephropathy. PMID:25415439

  4. Anti–microRNA-21 oligonucleotides prevent Alport nephropathy progression by stimulating metabolic pathways

    Science.gov (United States)

    Gomez, Ivan G.; MacKenna, Deidre A.; Johnson, Bryce G.; Kaimal, Vivek; Roach, Allie M.; Ren, Shuyu; Nakagawa, Naoki; Xin, Cuiyan; Newitt, Rick; Pandya, Shweta; Xia, Tai-He; Liu, Xueqing; Borza, Dorin-Bogdan; Grafals, Monica; Shankland, Stuart J.; Himmelfarb, Jonathan; Portilla, Didier; Liu, Shiguang; Chau, B. Nelson; Duffield, Jeremy S.

    2014-01-01

    MicroRNA-21 (miR-21) contributes to the pathogenesis of fibrogenic diseases in multiple organs, including the kidneys, potentially by silencing metabolic pathways that are critical for cellular ATP generation, ROS production, and inflammatory signaling. Here, we developed highly specific oligonucleotides that distribute to the kidney and inhibit miR-21 function when administered subcutaneously and evaluated the therapeutic potential of these anti–miR-21 oligonucleotides in chronic kidney disease. In a murine model of Alport nephropathy, miR-21 silencing did not produce any adverse effects and resulted in substantially milder kidney disease, with minimal albuminuria and dysfunction, compared with vehicle-treated mice. miR-21 silencing dramatically improved survival of Alport mice and reduced histological end points, including glomerulosclerosis, interstitial fibrosis, tubular injury, and inflammation. Anti–miR-21 enhanced PPARα/retinoid X receptor (PPARα/RXR) activity and downstream signaling pathways in glomerular, tubular, and interstitial cells. Moreover, miR-21 silencing enhanced mitochondrial function, which reduced mitochondrial ROS production and thus preserved tubular functions. Inhibition of miR-21 was protective against TGF-β–induced fibrogenesis and inflammation in glomerular and interstitial cells, likely as the result of enhanced PPARα/RXR activity and improved mitochondrial function. Together, these results demonstrate that inhibition of miR-21 represents a potential therapeutic strategy for chronic kidney diseases including Alport nephropathy. PMID:25415439

  5. Identification by molecular diagnosis of mosaic Turner's syndrome in an obligate carrier female for fragile X syndrome.

    OpenAIRE

    Tejada, M. I.; Mornet, E; Tizzano, E.; Molina, M.; Baiget, M; Boue, A

    1994-01-01

    A case of mosaic Turner's syndrome with a 45,X/46,XX/47,XXX karyotype, who was also a fragile X obligate carrier as the mother of an affected boy, was identified by molecular diagnosis. Complete haplotyping and direct DNA analysis showed that the X chromosome in all metaphases was the normal X. At the age of 57, she is mentally normal. Her external appearance was typical of Turner's syndrome. This report shows that molecular studies in conjunction with cytogenetic analysis can help in the cli...

  6. Angelman syndrome: review of clinical and molecular aspects

    Directory of Open Access Journals (Sweden)

    Bird LM

    2014-05-01

    Full Text Available Lynne M Bird1Department of Pediatrics, University of California, Division of Genetics, Rady Children’s Hospital, San Diego, California, USAAbstract: “Angelman syndrome” (AS is a neurodevelopmental disorder whose main features are intellectual disability, lack of speech, seizures, and a characteristic behavioral profile. The behavioral features of AS include a happy demeanor, easily provoked laughter, short attention span, hypermotoric behavior, mouthing of objects, sleep disturbance, and an affinity for water. Microcephaly and subtle dysmorphic features, as well as ataxia and other movement disturbances, are additional features seen in most affected individuals. AS is due to deficient expression of the ubiquitin protein ligase E3A (UBE3A gene, which displays paternal imprinting. There are four molecular classes of AS, and some genotype–phenotype correlations have emerged. Much remains to be understood regarding how insufficiency of E6-AP, the protein product of UBE3A, results in the observed neurodevelopmental deficits. Studies of mouse models of AS have implicated UBE3A in experience-dependent synaptic remodeling.Keywords: Angelman syndrome, chromosome 15q11-13, UBE3A, imprinting

  7. Cytogenetic and molecular studies of down syndrome individual with leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Shen, J.J.; Hassold, T.J. [Case Western Reserve Univ. School of Medicine, Cleveland, OH (United States); Williams, B.J. [Univ. of Utah School of Medicine, Salt Lake City, UT (United States); Zupursky, A.; Doyle, J. [Univ. of Toronto (Canada); Sherman, S.L. [Emory Univ. School of Medicine, Atlanta, GA (United States); Jacobs, P.A. [Salisbury District Hospital (United Kingdom); Shugar, A.L.; Soukup, S.W. [Univ. of Cincinnati, OH (United States)

    1995-04-01

    There is an increased risk of leukemia in Down syndrome (DS) patients, with estimates ranging from 14 to 30 times the incidence rate observed for chromosomally normal children. Furthermore, one type of leukemia, called {open_quotes}transient leukemia{close_quotes} (TL), occurs almost exclusively in DS infants. The basis of the association between DS and leukemia is unknown, but we and others have hypothesized that it may be influenced by the mechanism of origin of the extra chromosome. Therefore, we initiated a cytogenetic and molecular study of nondisjunction in leukemic DS individuals. To date, we have obtained blood and/or tissue samples from 55 individuals consisting of 17 cases with TL, 7 cases of acute nonlymphocytic leukemia subtype M7 (ANLL-M7, or acute megakaryoblastic leukemia, postulated to be related to TL), and 31 cases of other forms of leukemia. Analysis of these cases suggests differences between DS children with TL and those with other types of leukemia or DS individuals with no history of leukemia. Specifically, the TL and ANLL-M7 cases have a highly significant increase in the frequency of {open_quotes}atypical{close_quotes} constitutional karyotypes (i.e., mosaic trisomies, rings, and/or isochromosomes) and are almost always male. Additionally, genetic mapping studies suggest an increase in the frequency of disomic homozygosity, especially in proximal 21q, in DS individuals with TL and ANLL-M7. 19 refs., 3 figs., 4 tabs.

  8. Epstein syndrome with rapid progression to end stage renal disease

    Directory of Open Access Journals (Sweden)

    Alhindawi Esam

    2009-01-01

    Full Text Available The association of haematological abnormalities and hereditary nephritis is rare; it is mainly included in a spectrum of autosomal dominant macrothrombocytopenias: May-Hegglin anomaly, Fechtner, Sebastian, Epstein and Alport syndrome with macro thrombocytopenia. We are presenting a missed case of a boy who presented with epistaxis and his diagnostic work up revealed macrothrombocytopenia, sensorineural hearing loss and chronic nephropathy which constitute the Epstein syndrome, with rapid deterioration of kidney function.

  9. Usher syndrome: molecular links of pathogenesis, proteins and pathways.

    NARCIS (Netherlands)

    Kremer, H.; Wijk, E. van; Marker, T.; Wolfrum, U.; Roepman, R.

    2006-01-01

    Usher syndrome is the most common form of deaf-blindness. The syndrome is both clinically and genetically heterogeneous, and to date, eight causative genes have been identified. The proteins encoded by these genes are part of a dynamic protein complex that is present in hair cells of the inner ear a

  10. Recent discoveries in the molecular genetics of Lynch syndrome.

    Science.gov (United States)

    Boland, C Richard

    2016-07-01

    Lynch syndrome is the inherited predisposition to cancer caused by a germline mutation in a DNA mismatch repair gene. The consequent tumors have a characteristic microsatellite instability (MSI) phenotype. Genomic sequencing of Lynch syndrome-associated colorectal cancers (CRCs) has demonstrated that these tumors have a substantially greater number of mutations than non-MSI CRCs, and that the target mutations driving tumor behavior are also different from what occurs in sporadic tumors. There are multiple non-Lynch syndrome entities that can create clinical confusion with that disease, including the acquired methylation of MLH1, Lynch-like syndrome, and Familial CRC-Type X. Patients with Lynch syndrome-associated CRCs have a substantially better prognosis, and there is growing evidence that this is due to the generation of immunogenic frameshift peptides as a consequence of defective DNA mismatch repair, and an effective immune response to the tumor. PMID:27038793

  11. Fragile X syndrome. Molecular and clinical insights and treatment issues.

    OpenAIRE

    Hagerman, R.J.

    1997-01-01

    The fragile X syndrome is the most common inherited cause of mental retardation that is known. The prevalence of mental retardation from this syndrome ranges from 1 in 1,250 to 1 in 4,000 in the general population, although the prevalence of female carriers has been reported to be as high as 1 in 259. The discovery of the FMR1 gene mutation in 1991 has simplified diagnosis, enhanced our understanding of the spectrum of involvement in the fragile X syndrome, and stimulated research regarding t...

  12. Clinical and molecular cytogenetic (FISH) diagnosis of Williams syndrome.

    OpenAIRE

    Brewer, C. M.; Morrison, N; Tolmie, J L

    1996-01-01

    Sixteen children and adolescents with a firm clinical diagnosis of Williams syndrome were investigated with the chromosome fluorescence in situ hybridisation (FISH) technique employing the elastin gene probe. In each case there was a fluorescent signal on one chromosome 7 homologue only, indicating elastin gene deletion. No deletion was demonstrated in another child in whom an earlier diagnosis of Williams syndrome was judged doubtful at review. Firm clinical diagnosis correlates with elastin...

  13. Molecular Genetics of Williams Syndrome: Windows into Human Biology

    OpenAIRE

    Julie Korenberg

    2009-01-01

    Genetics is my favorite way of thinking: Williams syndrome seen through the eyes of a geneticist. Williams syndrome (WS) is the most compelling model in which to link the basis of human emotion and behavior to their biological origins. The explanatory power of human genetics in WS rests on the recent revolution in understanding the human genome but more specifically on the ability to link genetic with behavioral variation at high resolution. WS is due to the deletion of about 25 g...

  14. Assessment of High Molecular Weight Adiponectin and Interleukin-6 in Metabolic Syndrome

    OpenAIRE

    Delia Lupu; Dumitraşcu, Dan L.

    2014-01-01

    Background. Subclinical inflammation can represent a risk factor associated with the metabolic syndrome. Measurement of systemic inflammatory markers can improve early diagnosis in this disease. In the last decade different biomarkers have been suggested for the evaluation of inflammation in metabolic syndrome: high-sensitive C-reactive protein, leptin, tumor necrosis factor-alpha, total adiponectin.Aim. The aim of this study was to investigate a possible relationship between high molecular w...

  15. Molecular mechanism of metabolic syndrome X: contribution of adipocytokines adipocyte-derived bioactive substances.

    Science.gov (United States)

    Matsuzawa, Y; Funahashi, T; Nakamura, T

    1999-11-18

    Syndrome X is a clinical syndrome in which multiple risks cluster in an individual, and it is a common basis of vascular disease in the industrial countries. The molecular basis of Syndrome X, however, has not been elucidated. We have analyzed body fat distribution using CT scan and have shown that people who have accumulated intra-abdominal visceral fat frequently have multiple risks and vascular diseases. Thus, "visceral fat syndrome" is a clinical entity compatible with Syndrome X. To clarify the molecular mechanism of the disorders in visceral fat syndrome, we analyzed the expressed genes in adipose tissue by a large-scale random sequencing. Unexpectedly, visceral fat expressed a variety of the genes for secretory proteins including various bioactive substances; we designated them adipocytokines. One of them, plasminogen activator inhibitor-1, was overproduced in accumulated visceral fat and might contribute to the development of vascular disease. We have also cloned a novel adipose-specific gene named adiponectin. Adiponectin is a collagen-like plasma protein which has an inhibitory effect on proliferation of vascular smooth muscle cells; its plasma levels are paradoxically decreased in obesity. Adipocytokines may play important roles in the development of the disorders in Syndrome X. PMID:10842660

  16. Microphthalmia with linear skin defects (MLS) syndrome: Clinical, cytogenetic, and molecular characterization

    Energy Technology Data Exchange (ETDEWEB)

    Lindsay, E.A.; Grillo, A.; Ferrero, G.B.; Baldini, A.; Ballabio, A.; Zoghbi, H.Y.; Roth, E.J. [Baylor College of Medicine, Houston, TX (United States); Magenis, E.; Grompe, M. [Oregon Health Science Univ., Portland, OR (United States); Hulten, M. [East Birmingham Hospital, Birmingham (United Kingdom)] [and others

    1994-01-15

    The microphthalmia with linear skin defects (MLS) syndrome (MIM309801) is a severe developmental disorder observed in XX individuals with distal Xp segmental monosomy. The phenotype of this syndrome overlaps with that of both Aicardi (MIM 305050) and Goltz (MIM 305600) syndromes, two X-linked dominant, male-lethal disorders. Here the authors report the clinical, cytogenetic, and molecular characterization of 3 patients with this syndrome. Two of these patients are females with a terminal Xpter-p22.2 deletion. One of these 2 patients had an aborted fetus with anencephaly and the same chromosome abnormality. The third patient is an XX male with Xp/Yp exchange spanning the SRY gene which results in distal Xp monosomy. The extensive clinical variability observed in these patients and the results of the molecular analysis suggest that X-inactivation plays an important role in determining the phenotype of the MLS syndrome. The authors propose that the MLS, Aicardi, and Goltz syndromes are due to the involvement of the same gene(s), and that different patterns of X-inactivation are responsible for the phenotypic differences observed in these 3 disorders. However, they cannot rule out that each component of the MLS phenotype is caused by deletion of a different gene (a contiguous gene syndrome). 24 refs., 4 figs., 1 tab.

  17. Molecular analysis for diagnosis of Marfan syndrome and Marfan-associated disorders

    Institute of Scientific and Technical Information of China (English)

    GAO Ling-gen; YAO Xiu-ping; ZHANG Lin; HUI Ru-tai; ZHOU Xian-liang

    2011-01-01

    Marfan syndrome is a systemic disorder of connective tissue, caused by mutations in the FBN1, TGFBR1 or TGFBR2 genes. This syndrome is characterized by involvement of three major systems, skeletal, ocular, and cardiovascular. The continuing improvements in molecular biology and increasing availability of molecular diagnosis in clinical practice allow recognition of Marfan syndrome in patients with incomplete phenotypes. Additionally, molecular analyses could also be used for preimplantation genetic diagnosis. The identification of a mutation allows for early diagnosis, prognosis, genetic counseling, preventive management of carriers and reassurance for unaffected relatives. The importance of knowing in advance the location of the putative family mutation is highlighted by its straightforward application to prenatal and postnatal screening.

  18. Churg-Strauss vasculitis and idiopathic hypereosinophyl syndrome: role of molecular biology in the differential diagnosis of hypereosinophyl syndrome

    Directory of Open Access Journals (Sweden)

    A. d'Ascanio

    2011-09-01

    Full Text Available Objective: Hypereosinophilic syndromes are a heterogeneous group of uncommon disorders characterized by the presence of marked peripheral blood eosinophilia, tissue eosinophilia, or both, resulting in a wide variety of clinical manifestations, often without an identifiable cause. Churg-Strauss syndrome is a systemic vasculitis characterized by prominent peripheral eosinophilia, asthma and systemic involvement. The presence of mild to severe eosinophilia and systemic involvement raise the search of many trigger factor that need to be ruled out. Distinguishing CSS from idiopathic hypereosinophilic syndrome may be particularly challenging, especially in ANCA negative patients. Methods: The aim of the present study was to present a small case series of patients referred to a Rheumatology Unit for mild to severe eosinophilia and signs and symptoms of systemic involvement and to outline the clinical significance of molecular biology in the work-up of hypereosinophilia. Results: Eleven patients with moderate to severe peripheral eosinophylia, were referred to our Unit from 1996 to 2007. Female to male ratio was 7/4, mean age 40.54 (range 22-75. Three out of eleven patients resulted positive for molecular biology. The diagnosis of idiopathic hypereosinophylia was confirmed in one out of three on the basis of the clinical picture and bone marrow biopsy. Conclusions: Molecular biology may be useful in the screening and in the follow-up of a new hypereosinophylic patient.

  19. Mutations in MYH9 result in the May-Hegglin anomaly, and Fechtner and Sebastian syndromes. The May-Heggllin/Fechtner Syndrome Consortium.

    Science.gov (United States)

    Seri, M; Cusano, R; Gangarossa, S; Caridi, G; Bordo, D; Lo Nigro, C; Ghiggeri, G M; Ravazzolo, R; Savino, M; Del Vecchio, M; d'Apolito, M; Iolascon, A; Zelante, L L; Savoia, A; Balduini, C L; Noris, P; Magrini, U; Belletti, S; Heath, K E; Babcock, M; Glucksman, M J; Aliprandis, E; Bizzaro, N; Desnick, R J; Martignetti, J A

    2000-09-01

    The autosomal dominant, giant-platelet disorders, May-Hegglin anomaly (MHA; MIM 155100), Fechtner syndrome (FTNS; MIM 153640) and Sebastian syndrome (SBS), share the triad of thrombocytopenia, large platelets and characteristic leukocyte inclusions ('Döhle-like' bodies). MHA and SBS can be differentiated by subtle ultrastructural leukocyte inclusion features, whereas FTNS is distinguished by the additional Alport-like clinical features of sensorineural deafness, cataracts and nephritis. The similarities between these platelet disorders and our recent refinement of the MHA (ref. 6) and FTNS (ref. 7) disease loci to an overlapping region of 480 kb on chromosome 22 suggested that all three disorders are allelic. Among the identified candidate genes is the gene encoding nonmuscle myosin heavy chain 9 (MYH9; refs 8-10), which is expressed in platelets and upregulated during granulocyte differentiation. We identified six MYH9 mutations (one nonsense and five missense) in seven unrelated probands from MHA, SBS and FTNS families. On the basis of molecular modelling, the two mutations affecting the myosin head were predicted to impose electrostatic and conformational changes, whereas the truncating mutation deleted the unique carboxy-terminal tailpiece. The remaining missense mutations, all affecting highly conserved coiled-coil domain positions, imparted destabilizing electrostatic and polar changes. Thus, our results suggest that mutations in MYH9 result in three megakaryocyte/platelet/leukocyte syndromes and are important in the pathogenesis of sensorineural deafness, cataracts and nephritis. PMID:10973259

  20. Clinical and molecular phenotype of Aicardi-Goutieres syndrome

    DEFF Research Database (Denmark)

    Rice, Gillian; Patrick, Teresa; Parmar, Rekha;

    2007-01-01

    Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3'-->5' exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease com...

  1. Molecular analysis of the 18q- syndrome--and correlation with phenotype.

    OpenAIRE

    Kline, A D; White, M E; Wapner, R; Rojas, K; Biesecker, L G; Kamholz, J; Zackai, E. H.; Muenke, M; Scott, C I; Overhauser, J

    1993-01-01

    Seven individuals with deletions of the distal long arm of chromosome 18 were evaluated at the clinical, cytogenetic, and molecular levels. The patients had varying degrees of typical clinical findings associated with the 18q- syndrome. Cytogenetic analysis revealed deletions from 18q21.3 or 18q22.2 to qter. Somatic cell hybrids derived from the patients were molecularly characterized using ordered groups of probes isolated from a chromosome 18-specific library. In general, the size of the de...

  2. Molecular analysis of fragile X syndrome in Antalya Province

    OpenAIRE

    Bilgen T; Keser I; Mihci E; Haspolat S; Tacoy S; Luleci G

    2005-01-01

    Background: Detection of the (CGG)n repeats in the FMR1 gene that cause the fragile X syndrome (FXS), has become a milestone for phenotype-genotype correlation in FXS. Aims: To screen the FMR1 gene CGG repeats in index cases with FXS and their family members in the Antalya Province. Setting and design: This study was prospectively conducted between January 200and March 2005 in Department of Medical Biology and Genetics, Faculty of Medicine, Akdeniz University, Antalya. Materials and Method...

  3. Clinical and molecular features of Joubert syndrome and related disorders

    OpenAIRE

    Parisi, Melissa A.

    2009-01-01

    Joubert syndrome (JBTS; OMIM 213300) is a rare, autosomal recessive disorder characterized by a specific congenital malformation of the hindbrain and a broad spectrum of other phenotypic findings that is now known to be caused by defects in the structure and/or function of the primary cilium. The complex hindbrain malformation that is characteristic of JBTS can be identified on axial magnetic resonance imaging and is known as the molar tooth sign (MTS); other diagnostic criteria include intel...

  4. Molecular characterization of Blau syndrome: Genetic linkage to chromosome 16

    Energy Technology Data Exchange (ETDEWEB)

    Tromp, G.; Duivaniemi, H.; Christiano, A. [Thomas Jefferson Univ., Philadelphia, PA (United States)] [and others

    1994-09-01

    The Blau syndrome is an autosomal, dominantly-inherited disease characterized by multi-organ, tissue-specific inflammation. Its clinical phenotype includes granulomatous uveitis, arthritis and skin rash. The syndrome is unique in that it is the sole human model for a variety of multi-system inflammatory diseases that afflict a significant percentage of the population. Karyotypic analysis of the large, three generation kindred whose disease originally characterized the syndrome was unremarkable. Following exclusion of a number of extracellular matrix candidates genes, a genome-wide search was undertaken of the Blau susceptibility locus. Fifty-seven members of the family were genotyped for about 200 highly polymorphic dinucleotide repeat markers. Linkage analysis was performed using the LINKAGE package of programs under a model of dominant inheritance with reduced penetrance. Five liability classes were used to specify penetrances and phenocopy rates for those affected the arthritis, uveitis, skin rash and combinations thererof. In addition, five age-dependent penetrance classes were used for unaffected individuals. The marker D16S298 gave a maximum lod score of 3.6 at {theta} = 0.05 with two-point analysis. Lod scores for flanking markers were consistent. These data provide convincing evidence that the Blau susceptibility locus is situated within the 16p12-q21 interval. Fine mapping of the candidate interval with additional families exhibiting the Blau phenotype, as well as with more polymorphic markers, is underway.

  5. Cytogenetic and Molecular Investigation in Children with Possible Fragile X Syndrome

    Directory of Open Access Journals (Sweden)

    Onur Ozer

    2012-04-01

    Full Text Available Objective: Fragile X syndrome (FXS is the most common cause of inherited mental retardation and is due to a mutation in the X-linked FMR1 gene. Molecular genetic testing and chromosome analysis are indicated for this disorder. In this context, we tried to determine the frequency of the FXS, and other chro¬mosomal abnormalities of Turkish pediatric neurology outpatients. Materials and Methods: Cytogenetic and molecular screenings were performed to esti-mate the prevalence of the fragile X in 107 patients with mental retardation, language disorders, hyperactivity, develop¬mental delay or fragile X syndrome phenotype. Only 26 out of 107 patients were screened, molecularly. Results: Cytogenetically fragile X-positive cells was found in 8 cases (7.5% of 107 patients; in 4.7% of males and in 2.8% of females. The autosomal fragile sites (FS was found in 14 (13.1% cases. One (0.9% patient had pericentric inversion of chromosome 9. Molecular analysis were performed for 26 patients and all patients showed normal CGG expansion. Conclusion: In diagnosis of fragile X syndrome, chromosome analysis must be run in conjunction with the molecular studies. It is recommended that all members of the fragile X family under risk should be screened both by cytogenetic and molecular methods. Genetic counseling can be useful to patients and families considering genetic testing. [Cukurova Med J 2012; 37(2.000: 76-83

  6. Shigatoxin-associated hemolytic uremic syndrome: current molecular mechanisms and future therapies

    Directory of Open Access Journals (Sweden)

    Keir LS

    2012-07-01

    Full Text Available Lindsay S Keir,1 Stephen D Marks,2 Jon Jin Kim21Academic Renal Unit, University of Bristol, Bristol; 2Department of Paediatric Nephrology, Great Ormond Street Hospital NHS Foundation Trust, London, United KingdomAbstract: Hemolytic uremic syndrome is the leading cause of acute kidney injury in childhood. Ninety percent of cases are secondary to gastrointestinal infection with shigatoxin-producing bacteria. In this review, we discuss the molecular mechanisms of shigatoxin leading to hemolytic uremic syndrome and the emerging role of the complement system and vascular endothelial growth factor in its pathogenesis. We also review the evidence for treatment options to date, in particular antibiotics, plasma exchange, and immunoadsorption, and link this to the molecular pathology. Finally, we discuss future avenues of treatment, including shigatoxin-binding agents and complement inhibitors, such as eculizumab.Keywords: hemolytic uremic syndrome, shigatoxin, diarrhea, Escherichia coli, complement, alternative pathway, eculizumab

  7. 22q13.3 Deletion Syndrome : Clinical and Molecular Analysis Using Array CGH

    NARCIS (Netherlands)

    Dhar, S. U.; del Gaudio, D.; German, J. R.; Peters, S. U.; Ou, Z.; Bader, P. I.; Berg, J. S.; Blazo, M.; Brown, C. W.; Graham, B. H.; Grebe, T. A.; Lalani, S.; Irons, M.; Sparagana, S.; Williams, M.; Phillips, J. A.; Beaudet, A. L.; Stankiewicz, P.; Patel, A.; Cheung, S. W.; Sahoo, T.

    2010-01-01

    The 22q13.3 deletion syndrome results from loss of terminal segments of varying sizes at 22qter. Few genotype phenotype correlations have been found but all patients have mental retardation and severe delay, or absence of, expressive speech. We carried out clinical and molecular characterization of

  8. Clinical and molecular delineation of the 17q21.31 microdeletion syndrome.

    NARCIS (Netherlands)

    Koolen, D.A.; Sharp, A.J.; Hurst, J.A.; Firth, H.V.; Knight, S.J.; Goldenberg, A.; Saugier-Veber, P.; Pfundt, R.P.; Vissers, L.E.L.M.; Destree, A.; Grisart, B.; Rooms, L.; Aa, N. van der; Field, M.; Hackett, A.; Bell, K.; Nowaczyk, M.J.; Mancini, G.M.; Poddighe, P.J.; Schwartz, C.E.; Rossi, E.; Gregori, M. de; Antonacci-Fulton, L.L.; McLellan, MD2nd; Garrett, J.M.; Wiechert, M.A.; Miner, T.L.; Crosby, S.; Ciccone, R.; Willatt, L.; Rauch, A.; Zenker, M.; Aradhya, S.; Manning, M.A.; Strom, T.M.; Wagenstaller, J.; Krepischi-Santos, A.C.; Vianna-Morgante, A.M.; Rosenberg, C.; Price, S.M.; Stewart, H.; Shaw-Smith, C.; Brunner, H.G.; Wilkie, A.O.; Veltman, J.A.; Zuffardi, O.; Eichler, E.E.; Vries, L.B.A. de

    2008-01-01

    BACKGROUND: The chromosome 17q21.31 microdeletion syndrome is a novel genomic disorder that has originally been identified using high resolution genome analyses in patients with unexplained mental retardation. AIM: We report the molecular and/or clinical characterisation of 22 individuals with the 1

  9. Birt-Hogg-Dubé syndrome: Clinical and molecular aspects of recently identified kidney cancer syndrome.

    Science.gov (United States)

    Hasumi, Hisashi; Baba, Masaya; Hasumi, Yukiko; Furuya, Mitsuko; Yao, Masahiro

    2016-03-01

    Birt-Hogg-Dubé syndrome is an autosomal dominantly inherited disease that predisposes patients to develop fibrofolliculoma, lung cysts and bilateral multifocal renal tumors, histologically hybrid oncocytic/chromophobe tumors, chromophobe renal cell carcinoma, oncocytoma, papillary renal cell carcinoma and clear cell renal cell carcinoma. The predominant forms of Birt-Hogg-Dubé syndrome-associated renal tumors, hybrid oncocytic/chromophobe tumors and chromophobe renal cell carcinoma are typically less aggressive, and a therapeutic principle for these tumors is a surgical removal with nephron-sparing. The timing of surgery is the most critical element for postoperative renal function, which is one of the important prognostic factors for Birt-Hogg-Dubé syndrome patients. The folliculin gene (FLCN) that is responsible for Birt-Hogg-Dubé syndrome was isolated as a novel tumor suppressor for kidney cancer. Recent studies using murine models for FLCN, a protein encoded by the FLCN gene, and its two binding partners, folliculin-interacting protein 1 (FNIP1) and folliculin-interacting protein 2 (FNIP2), have uncovered important roles for FLCN, FNIP1 and FNIP2 in cell metabolism, which include AMP-activated protein kinase-mediated energy sensing, Ppargc1a-driven mitochondrial oxidative phosphorylation and mTORC1-dependent cell proliferation. Birt-Hogg-Dubé syndrome is a hereditary hamartoma syndrome, which is triggered by metabolic alterations under a functional loss of FLCN/FNIP1/FNIP2 complex, a critical regulator of kidney cell proliferation rate; a mechanistic insight into the FLCN/FNIP1/FNIP2 pathway could provide us a basis for developing new therapeutics for kidney cancer. PMID:26608100

  10. Tetrasomy 21 pter {yields} q22.1 and Down syndrome: Molecular definition of the region

    Energy Technology Data Exchange (ETDEWEB)

    Daumer-Haas, C.; Schuffenhauer, S.; Walther, J.U. [Universitaet Muenchen (Germany); Portsmann, T. [Humboldt Universitaet, Berlin (Germany); Korenberg, J.R.; Schipper, R.D. [Univ. of California, Los Angeles, CA (United States)

    1994-12-01

    Down syndrome is usually caused by complete trisomy 21. Rarely, it is due to partial trisomy of the segment 21q22. We report on a 33-month-old girl with tetrasomy 21 pter {yields} q22.1 resulting from an extra chromosome idic(21)(q22.1). She has craniofacial traits typical of Down syndrome, including brachycephaly, third fontanel, upward slanting palpebral fissures, round face, and protruding tongue. Speech development is quite delayed whereas motor development is only mildly retarded. The molecular content of the extra isodicentric chromosome was defined by molecular genetic investigations using 13 single copy probes unique to chromosome 21, and SOD1 expression studies. The child was found to have 4 copies of the region defined by D21S16 (21cen) through D21S93 on 21q22.1 and two copies of the remaining region defined by SOD1 {yields} D21S55 {yields} D21S123. In view of the recent assignment of Down syndrome facial characters to the 21q22 region, defined in part by D21S55, it is significant that this child shows a subset of Down syndrome facial manifestations, without duplication of this region. These results suggest that genes contributing to the facial and some of the hand manifestations of Down syndrome also exist in the chromosomal region proximal to D21S55 in band 21q22.1. 34 refs., 6 figs., 3 tabs.

  11. Apert and Crouzon syndromes-Cognitive development, brain abnormalities, and molecular aspects.

    Science.gov (United States)

    Fernandes, Marilyse B L; Maximino, Luciana P; Perosa, Gimol B; Abramides, Dagma V M; Passos-Bueno, Maria Rita; Yacubian-Fernandes, Adriano

    2016-06-01

    Apert and Crouzon are the most common craniosynostosis syndromes associated with mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. We conducted a study to examine the molecular biology, brain abnormalities, and cognitive development of individuals with these syndromes. A retrospective longitudinal review of 14 patients with Apert and Crouzon syndromes seen at the outpatient Craniofacial Surgery Hospital for Rehabilitation of Craniofacial Anomalies in Brazil from January 1999 through August 2010 was performed. Patients between 11 and 36 years of age (mean 18.29 ± 5.80), received cognitive evaluations, cerebral magnetic resonance imaging, and molecular DNA analyses. Eight patients with Apert syndrome (AS) had full scale intelligence quotients (FSIQs) that ranged from 47 to 108 (mean 76.9 ± 20.2), and structural brain abnormalities were identified in five of eight patients. Six patients presented with a gain-of-function mutation (p.Ser252Trp) in FGFR2 and FSIQs in those patients ranged from 47 to78 (mean 67.2 ± 10.7). One patient with a gain-of-function mutation (p.Pro253Arg) had a FSIQ of 108 and another patient with an atypical splice mutation (940-2A →G) had a FSIQ of 104. Six patients with Crouzon syndrome had with mutations in exons IIIa and IIIc of FGFR2 and their FSIQs ranged from 82 to 102 (mean 93.5 ± 6.7). These reveal that molecular aspects are another factor that can be considered in studies of global and cognitive development of patients with Apert and Crouzon syndrome (CS). © 2016 Wiley Periodicals, Inc. PMID:27028366

  12. Alport familial nephritis. Absence of 28 kilodalton non-collagenous monomers of type IV collagen in glomerular basement membrane.

    OpenAIRE

    Kleppel, M M; Kashtan, C. E.; Butkowski, R J; Fish, A. J.; Michael, A. F.

    1987-01-01

    Alport-type familial nephritis (FN), a genetic disorder, results in progressive renal insufficiency and sensorineural hearing loss. Immunochemical and biochemical analyses of the non-collagenous (NC1) domain of type IV collagen isolated from the glomerular basement membranes (GBM) of three males with this disease demonstrate absence of the normally occurring 28-kilodalton (kD) NC1 monomers, but persistence of the 26- and 24-kD monomeric subunits derived from alpha 1 and 2 (both type IV) colla...

  13. HNPCC (Lynch Syndrome: Differential Diagnosis, Molecular Genetics and Management - a Review

    Directory of Open Access Journals (Sweden)

    Lynch Henry T

    2003-12-01

    Full Text Available Abstract HNPCC (Lynch syndrome is the most common form of hereditary colorectal cancer (CRC, wherein it accounts for between 2-7 percent of the total CRC burden. When considering the large number of extracolonic cancers integral to the syndrome, namely carcinoma of the endometrium, ovary, stomach, hepatobiliary system, pancreas, small bowel, brain tumors, and upper uroepithelial tract, these estimates of its frequency are likely to be conservative. The diagnosis is based upon its natural history in concert with a comprehensive cancer family history inclusive of all anatomic sites. In order for surveillance and management to be effective and, indeed, lifesaving, among these high-risk patients, the linchpin to cancer control would be the physician, who must be knowledgeable about hereditary cancer syndromes, their molecular and medical genetics, genetic counseling, and, most importantly, the natural history of the disorders, so that the entirety of this knowledge can be melded to highly-targeted management.

  14. Hematopoietic Acute Radiation Syndrome (Bone marrow syndrome, Aplastic Anemia): Molecular Mechanisms of Radiation Toxicity.

    Science.gov (United States)

    Popov, Dmitri

    Key Words: Aplastic Anemia (AA), Pluripotential Stem Cells (PSC) Introduction: Aplastic Anemia (AA) is a disorder of the pluripotential stem cells involve a decrease in the number of cells of myeloid, erythroid and megakaryotic lineage [Segel et al. 2000 ]. The etiology of AA include idiopathic cases and secondary aplastic anemia after exposure to drugs, toxins, chemicals, viral infections, lympho-proliferative diseases, radiation, genetic causes, myelodisplastic syndromes and hypoplastic anemias, thymomas, lymphomas. [Brodskyet al. 2005.,Modan et al. 1975., Szklo et al. 1975]. Hematopoietic Acute Radiation Syndrome (or Bone marrow syndrome, or Radiation-Acquired Aplastic Anemia) is the acute toxic syndrome which usually occurs with a dose of irradiation between 0.7 and 10 Gy (70- 1000 rads), depending on the species irradiated. [Waselenko et al., 2004]. The etiology of bone morrow damage from high-level radiation exposure results depends on the radiosensitivity of certain bone marrow cell lines. [Waselenko et al. 2004] Aplastic anemia after radiation exposure is a clinical syndrome that results from a marked disorder of bone marrow blood cell production. [Waselenko et al. 2004] Radiation hematotoxicity is mediated via genotoxic and other specific toxic mechanisms, leading to aplasia, cell apoptosis or necrosis, initiation via genetic mechanisms of clonal disorders, in cases such as the acute radiation-acquired form of AA. AA results from radiation injury to pluripotential and multipotential stem cells in the bone marrow. The clinical signs displayed in reticulocytopenia, anemia, granulocytopenia, monocytopenia, and thrombocytopenia. The number of marrow CD34+ cells (multipotential hematopoietic progenitors) and their derivative colony-forming unit{granulocyte-macrophage (CFU-GM) and burst forming unit {erythroid (BFU{E) are reduced markedly in patients with AA. [Guinan 2011, Brodski et al. 2005, Beutler et al.,2000] Cells expressing CD34 (CD34+ cell) are normally

  15. Molecular and Cellular Mechanisms Elucidating Neurocognitive Basis of Functional Impairments Associated with Intellectual Disability in Down Syndrome

    Science.gov (United States)

    Rachidi, Mohammed; Lopes, Carmela

    2010-01-01

    Down syndrome, the most common genetic cause of intellectual disability, is associated with brain disorders due to chromosome 21 gene overdosage. Molecular and cellular mechanisms involved in the neuromorphological alterations and cognitive impairments are reported herein in a global model. Recent advances in Down syndrome research have lead to…

  16. Establishment of a Nonradioactive Molecular Diagnosis of Fragile-X Syndrome

    OpenAIRE

    Uyguner, Zehra Oya

    2000-01-01

    Fragile-X syndrome is a hereditary dynamic mutation disorder, predominantly caused by a large expansion of CGG trinucleotide repeats in the FMR 1 gene leading to methylation and down regulation of transcription of the gene. For the molecular diagnosis of the disease, the repeat locus in FMR 1 gene is primarily detected by Southern blotting with radioactively labeled probes. Unusually GC rich composition of the expanded region caused technical difficulties during PCR based testing a...

  17. Shwachman-Diamond syndrome: first molecular diagnosis in a Brazilian child

    OpenAIRE

    Cresio Alves; Julia Constanca Fernandes; Silvana Sampaio; Raquel de Melo Alves Paiva; Rodrigo Tocantins Calado

    2013-01-01

    Herein the first molecular diagnosis of a Brazilian child with Shwachman-Diamond Syndrome is reported. A 6-year-old boy was diagnosed with cystic fibrosis at the age of 15 months due to recurrent respiratory infections, diarrhea and therapeutic response to pancreatic enzymes. Three sweat tests were negative. At the age of 5 years, he began to experience pain in the lower limbs, laxity of joints, lameness and frequent falls. A radiological study revealed metaphyseal chondrodysplasia. A complet...

  18. The Molecular Dissection of Contiguous Gene Syndromes with a Focus on 4p16 Deletion Syndrome

    OpenAIRE

    Hannes, Femke

    2011-01-01

    Genotype-phenotype correlations were initially used to identify the minimal region of overlap between differently sized rearrangements in association with a specific phenotypic feature. This approach enabled the molecular dissection of the disease. However, the detection of the genotype by low resolution cytogenetic techniques hampered accurate genotype-phenotype correlations and the search for causative genes. With the advent of micro-array technology, the genotypes were more easily obtained...

  19. Practice guidelines for the molecular analysis of Prader-Willi and Angelman syndromes

    Directory of Open Access Journals (Sweden)

    Birch Rachael

    2010-05-01

    Full Text Available Abstract Background Prader-Willi syndrome (PWS and Angelman syndrome (AS are clinically distinct neurodevelopmental genetic disorders that map to 15q11-q13. The primary phenotypes are attributable to loss of expression of imprinted genes within this region which can arise by means of a number of mechanisms. The most sensitive single approach to diagnosing both PWS and AS is to study methylation patterns within 15q11-q13; however many techniques exist for this purpose. Given the diversity of techniques available, there is a need for consensus testing and reporting guidelines. Methods Testing and reporting guidelines have been drawn up and agreed in accordance with the procedures of the UK Clinical Molecular Genetics Society and the European Molecular Genetics Quality Network. Results A practical set of molecular genetic testing and reporting guidelines has been developed for these two disorders. In addition, advice is given on appropriate reporting policies, including advice on test sensitivity and recurrence risks. In considering test sensitivity, the possibility of differential diagnoses is discussed. Conclusion An agreed set of practice guidelines has been developed for the diagnostic molecular genetic testing of PWS and AS.

  20. Clinical and molecular characterization of two patients with palmoplantar keratoderma-congenital alopecia syndrome type 2.

    Science.gov (United States)

    Castori, M; Morlino, S; Sana, M E; Paradisi, M; Tadini, G; Angioni, A; Malacarne, M; Grammatico, P; Iascone, M; Forzano, F

    2016-08-01

    Palmoplantar keratoderma-congenital alopecia (PPKCA) syndrome is a rare genodermatosis, with two clinically recognizable forms: dominant (Type 1) and recessive (Type 2). Reports of only 18 patients have been published to date, and the molecular basis of the condition is unknown. We describe two cases with PPKCA Type 2 (PPKCA2), comprising a novel patient, originally reported as an example of autosomal ichthyosis follicularis-atrichia-photophobia syndrome, and the 6-year follow-up of a previously published case. Extensive molecular studies of both patients excluded mutations in all the known genes associated with PPK and partially overlapping syndromes. The striking similarities between these two patients confirm PPKCA2 as a discrete genodermatosis, of which the main features are congenital and universal alopecia, diffuse keratosis pilaris, facial erythema, and a specific PPK with predominant involvement of the fingertips and borders of the hands and feet, with evolution of sclerodactyly, contractures and constrictions. Clinical follow-up of these patients has demonstrated progressive worsening of the hand involvement and attenuation of facial erythema. PMID:27339777

  1. Síndrome de Alport: reporte de caso y revisión

    Directory of Open Access Journals (Sweden)

    José Augusto Urrego-Díaz

    2015-01-01

    Full Text Available Se presenta el caso de una paciente de 4 años de edad, con hermano gemelo dicigoto asintomático, hija de padres no consanguíneos y sin antecedentes familiares de enfermedad renal. Inicia su cuadro clínico con edemas y proteinuria severa como manifestación de un síndrome nefrótico primario de cambios mínimos; este se diagnosticó por biopsia renal y, en un principio, se manejó con esteroides. Su evolución no fue adecuada debido a múltiples recaídas que la clasificaron como síndrome nefrótico corticorresistente. Por ello, se requirió un cambio en su tratamiento y una segunda biopsia renal, cuyo resultado histológico sorprendió al grupo médico tratante porque los cambios en la membrana basal glomerular confirmaban que se trataba de un Síndrome de Alport.

  2. Molecular genetics of experimental hypertension and the metabolic syndrome: from gene pathways to new therapies

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Kurtz, T. W.

    2007-01-01

    Roč. 49, č. 5 (2007), s. 941-952. ISSN 0194-911X R&D Projects: GA MZd(CZ) NR8545; GA ČR(CZ) GA301/04/0390; GA ČR(CZ) GA301/06/0028 Grant ostatní: The Howard Hughes Institute(US) HHMI55005624 Institutional research plan: CEZ:AV0Z50110509 Keywords : SHR * CD36 * metabolic syndrome Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.194, year: 2007

  3. Clinical and Molecular Phenotype of Aicardi-Goutières Syndrome

    OpenAIRE

    Rice, Gillian ; Patrick, Teresa ; Parmar, Rekha ; Taylor, Claire F. ; Aeby, Alec ; Aicardi, Jean ; Artuch, Rafael ; Montalto, Simon Attard ; Bacino, Carlos A. ; Barroso, Bruno ; Baxter, Peter ; Benko, Willam S. ; Bergmann, Carsten ; Bertini, Enrico ; Biancheri, Roberta 

    2007-01-01

    Aicardi-Goutières syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3′→5′ exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B...

  4. Molecular definition of a region of chromosome 21 that causes features of the Down syndrome phenotype

    OpenAIRE

    Korenberg, Julie R; Kawashima, Hiroko; Pulst, Stefan-M.; Ikeuchi, T; Ogasawara, N; Yamamoto, K.; Schonberg, Steven A.; West, Ruth; Allen, Leland; Magenis, Ellen; Ikawa, K; Taniguchi, N; Epstein, Charles J.

    1990-01-01

    Down syndrome (DS) is a major cause of mental retardation and heart disease. Although it is usually caused by the presence of an extra chromosome 21, a subset of the diagnostic features may be caused by the presence of only band 21q22. We now present evidence that significantly narrows the chromosomal region responsible for several of the phenotypic features of DS. We report a molecular and cytogenetic analysis of a three-generation family containing four individuals with clinical DS as manif...

  5. Molecular biological analysis of genotyping and phylogeny of severe acute respiratory syndrome associated coronavirus

    Institute of Scientific and Technical Information of China (English)

    王志刚; 李兰娟; 罗芸; 张俊彦; 王敏雅; 程苏云; 张严峻; 王晓萌; 卢亦愚; 吴南屏; 梅玲玲; 王赞信

    2004-01-01

    Background SARS-CoV is the causative agent of severe acute respiratory syndrome (SARS) which has been associated with outbreaks of SARS in Guangdong, Hong Kong and Beijing of China, and other regions worldwide. SARS-CoV from human has shown some variations but its origin is still unknown. The genotyping and phylogeny of SARS-CoV were analyzed and reported in this paper. Methods Full or partial genomes of 44 SARS-CoV strains were collected from GenBank. The genotype, single nucleotide polymorphism and phylogeny of these SARS-CoV strains were analyzed by molecular biological, bioinformatic and epidemiological methods. Conclusion The results mentioned above suggest that SARS-CoV is responding to host immunological pressures and experiencing variation which provide clues, information and evidence of molecular biology for the clinical pathology, vaccine developing and epidemic investigation.

  6. Kidney and heart interactions during cardiorenal syndrome: a molecular and clinical pathogenic framework.

    Science.gov (United States)

    Napoli, Claudio; Casamassimi, Amelia; Crudele, Valeria; Infante, Teresa; Abbondanza, Ciro

    2011-07-01

    The heart and kidney are physiologically interconnected. Cardiorenal syndrome (CRS) is a pathological disorder where acute or chronic dysfunction in one organ may induce dysfunction in the other one. Although classical studies have proposed a role for hypertension, dyslipidemia and endothelial dysfunction, CRS should be considered as a complex molecular interplay of neurohumoral pathway activation including the sympathetic nervous system, the renin angiotensin aldosterone axis, the endothelin system and the arginine vasopressin system. This activation may induce vascular inflammation, oxidative stress, accelerated atherosclerosis, cardiac hypertrophy and both myocardial and intrarenal fibrosis with progression of CRS treatment. More recently, epigenetics has opened new pathogenic molecular routes for CRS. This will lead to a more rapid development of novel, safe and effective clinical therapies. PMID:21797745

  7. Conservation of nucleotide sequences for molecular diagnosis of Middle East respiratory syndrome coronavirus, 2015

    Directory of Open Access Journals (Sweden)

    Yuki Furuse

    2015-11-01

    Full Text Available Infection due to the Middle East respiratory syndrome coronavirus (MERS-CoV is widespread. The present study was performed to assess the protocols used for the molecular diagnosis of MERS-CoV by analyzing the nucleotide sequences of viruses detected between 2012 and 2015, including sequences from the large outbreak in eastern Asia in 2015. Although the diagnostic protocols were established only 2 years ago, mismatches between the sequences of primers/probes and viruses were found for several of the assays. Such mismatches could lead to a lower sensitivity of the assay, thereby leading to false-negative diagnosis. A slight modification in the primer design is suggested. Protocols for the molecular diagnosis of viral infections should be reviewed regularly after they are established, particularly for viruses that pose a great threat to public health such as MERS-CoV.

  8. Molecular Diagnosis of Hemorrhagic Fever with Renal Syndrome Caused by Puumala Virus

    Science.gov (United States)

    Lagerqvist, Nina; Hagström, Åsa; Lundahl, Malin; Nilsson, Elin; Juremalm, Mikael; Larsson, Inger; Alm, Erik; Bucht, Göran; Ahlm, Clas

    2016-01-01

    Rodent-borne hantaviruses cause two severe acute diseases: hemorrhagic fever with renal syndrome (HFRS) in Eurasia, and hantavirus pulmonary syndrome (HPS; also called hantavirus cardiopulmonary syndrome [HCPS]) in the Americas. Puumala virus (PUUV) is the most common causative agent of HFRS in Europe. Current routine diagnostic methods are based on serological analyses and can yield inconclusive results. Hantavirus-infected patients are viremic during the early phase of disease; therefore, detection of viral RNA genomes can be a valuable complement to existing serological methods. However, the high genomic sequence diversity of PUUV has hampered the development of molecular diagnostics, and currently no real-time reverse transcription-quantitative (RT)-PCR assay is available for routine diagnosis of HFRS. Here, we present a novel PUUV RT-PCR assay. The assay was validated for routine diagnosis of HFRS on samples collected in Sweden during the winter season from 2013 to 2014. The assay allowed detection of PUUV RNA in 98.7% of confirmed clinical HFRS samples collected within 8 days after symptomatic onset. In summary, this study shows that real-time RT-PCR can be a reliable alternative to serological tests during the early phase of HFRS. PMID:26962084

  9. Molecular Diagnosis of Hemorrhagic Fever with Renal Syndrome Caused by Puumala Virus.

    Science.gov (United States)

    Lagerqvist, Nina; Hagström, Åsa; Lundahl, Malin; Nilsson, Elin; Juremalm, Mikael; Larsson, Inger; Alm, Erik; Bucht, Göran; Ahlm, Clas; Klingström, Jonas

    2016-05-01

    Rodent-borne hantaviruses cause two severe acute diseases: hemorrhagic fever with renal syndrome (HFRS) in Eurasia, and hantavirus pulmonary syndrome (HPS; also called hantavirus cardiopulmonary syndrome [HCPS]) in the Americas. Puumala virus (PUUV) is the most common causative agent of HFRS in Europe. Current routine diagnostic methods are based on serological analyses and can yield inconclusive results. Hantavirus-infected patients are viremic during the early phase of disease; therefore, detection of viral RNA genomes can be a valuable complement to existing serological methods. However, the high genomic sequence diversity of PUUV has hampered the development of molecular diagnostics, and currently no real-time reverse transcription-quantitative (RT)-PCR assay is available for routine diagnosis of HFRS. Here, we present a novel PUUV RT-PCR assay. The assay was validated for routine diagnosis of HFRS on samples collected in Sweden during the winter season from 2013 to 2014. The assay allowed detection of PUUV RNA in 98.7% of confirmed clinical HFRS samples collected within 8 days after symptomatic onset. In summary, this study shows that real-time RT-PCR can be a reliable alternative to serological tests during the early phase of HFRS. PMID:26962084

  10. Understanding the molecular mechanisms of human microtia via a pig model of HOXA1 syndrome

    Directory of Open Access Journals (Sweden)

    Ruimin Qiao

    2015-06-01

    Full Text Available Microtia is a congenital malformation of the outer ears. Although both genetic and environmental components have been implicated in microtia, the genetic causes of this innate disorder are poorly understood. Pigs have naturally occurring diseases comparable to those in humans, providing exceptional opportunity to dissect the molecular mechanism of human inherited diseases. Here we first demonstrated that a truncating mutation in HOXA1 causes a monogenic disorder of microtia in pigs. We further performed RNA sequencing (RNA-Seq analysis on affected and healthy pig embryos (day 14.25. We identified a list of 337 differentially expressed genes (DEGs between the normal and mutant samples, shedding light on the transcriptional network involving HOXA1. The DEGs are enriched in biological processes related to cardiovascular system and embryonic development, and neurological, renal and urological diseases. Aberrant expressions of many DEGs have been implicated in human innate deformities corresponding to microtia-associated syndromes. After applying three prioritizing algorithms, we highlighted appealing candidate genes for human microtia from the 337 DEGs. We searched for coding variants of functional significance within six candidate genes in 147 microtia-affected individuals. Of note, we identified one EVC2 non-synonymous mutation (p.Asp1174Asn as a potential disease-implicating variant for a human microtia-associated syndrome. The findings advance our understanding of the molecular mechanisms underlying human microtia, and provide an interesting example of the characterization of human disease-predisposing variants using pig models.

  11. Clinical and molecular survey in 124 Chinese patients with Leigh or Leigh-like syndrome.

    Science.gov (United States)

    Zhang, Y; Yang, Y L; Sun, F; Cai, X; Qian, N; Yuan, Y; Wang, Z X; Qi, Y; Xiao, J X; Wang, X Y; Zhang, Y H; Jiang, Y W; Qin, J; Wu, X R

    2007-04-01

    Leigh syndrome is the most common mitochondrial disorder in children characterized by necrotic lesions in the central nervous system. Both mitochondrial DNA (mtDNA) and nuclear DNA defects in the mitochondrial respiratory chain can lead to this disease. To characterize the clinical and genetic traits of Leigh or Leigh-like syndrome patients in China, 124 unrelated cases were collected between 1992 and 2005. Seventy-seven cases (62.1%) met the typical criteria of Leigh syndrome, including symmetrical bilateral abnormal signals in the basal ganglia, thalamus and brain stem, etc. Other cases (37.9%) belonged to Leigh-like syndrome with atypical clinical or radiological manifestations. Late-onset patients accounted for 20.2%, which is more than previously reported. Movement disorder was the most common symptoms in our patients. Thirty-two patients (25.8%) were confirmed to carry mutant genes. Among them, six cases (4.8%) have been demonstrated to have point mutations in mitochondrial DNA. Two separate patients were detected to have mutations on A8344G and A3243G. The T8993G point mutation was identified in one patient and T8993C in one other patient. SURF1 mutations associated with cytochrome-c oxidase deficiency were identified in 25 patients (20.2%). Four unreported variations have been identified in SURF1 gene from three patients. G604C was found in 22 patients. Only one patient had C214T mutation in the pyruvate dehydrogenase E1alpha subunit gene. In the remaining 92 patients (74.2%), a specific molecular dysfunction or underlying metabolic abnormality could not be identified. PMID:17323145

  12. Standard and AEGIS nicking molecular beacons detect amplicons from the Middle East respiratory syndrome coronavirus.

    Science.gov (United States)

    Yaren, Ozlem; Glushakova, Lyudmyla G; Bradley, Kevin M; Hoshika, Shuichi; Benner, Steven A

    2016-10-01

    This paper combines two advances to detect MERS-CoV, the causative agent of Middle East Respiratory Syndrome, that have emerged over the past few years from the new field of "synthetic biology". Both are based on an older concept, where molecular beacons are used as the downstream detection of viral RNA in biological mixtures followed by reverse transcription PCR amplification. The first advance exploits the artificially expanded genetic information systems (AEGIS). AEGIS adds nucleotides to the four found in standard DNA and RNA (xNA); AEGIS nucleotides pair orthogonally to the A:T and G:C pairs. Placing AEGIS components in the stems of molecular beacons is shown to lower noise by preventing unwanted stem invasion by adventitious natural xNA. This should improve the signal-to-noise ratio of molecular beacons operating in complex biological mixtures. The second advance introduces a nicking enzyme that allows a single target molecule to activate more than one beacon, allowing "signal amplification". Combining these technologies in primers with components of a self-avoiding molecular recognition system (SAMRS), we detect 50 copies of MERS-CoV RNA in a multiplexed respiratory virus panel by generating fluorescence signal visible to human eye and/or camera. PMID:27421627

  13. The molecular basis of variable phenotypic severity among common missense mutations causing Rett syndrome.

    Science.gov (United States)

    Brown, Kyla; Selfridge, Jim; Lagger, Sabine; Connelly, John; De Sousa, Dina; Kerr, Alastair; Webb, Shaun; Guy, Jacky; Merusi, Cara; Koerner, Martha V; Bird, Adrian

    2016-02-01

    Rett syndrome is caused by mutations in the X-linked MECP2 gene, which encodes a chromosomal protein that binds to methylated DNA. Mouse models mirror the human disorder and therefore allow investigation of phenotypes at a molecular level. We describe an Mecp2 allelic series representing the three most common missense Rett syndrome (RTT) mutations, including first reports of Mecp2[R133C] and Mecp2[T158M] knock-in mice, in addition to Mecp2[R306C] mutant mice. Together these three alleles comprise ∼25% of all RTT mutations in humans, but they vary significantly in average severity. This spectrum is mimicked in the mouse models; R133C being least severe, T158M most severe and R306C of intermediate severity. Both R133C and T158M mutations cause compound phenotypes at the molecular level, combining compromised DNA binding with reduced stability, the destabilizing effect of T158M being more severe. Our findings contradict the hypothesis that the R133C mutation exclusively abolishes binding to hydroxymethylated DNA, as interactions with DNA containing methyl-CG, methyl-CA and hydroxymethyl-CA are all reduced in vivo. We find that MeCP2[T158M] is significantly less stable than MeCP2[R133C], which may account for the divergent clinical impact of the mutations. Overall, this allelic series recapitulates human RTT severity, reveals compound molecular aetiologies and provides a valuable resource in the search for personalized therapeutic interventions. PMID:26647311

  14. Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes

    OpenAIRE

    Hytönen, Marjo K.; Meharji Arumilli; Lappalainen, Anu K; Marta Owczarek-Lipska; Vidhya Jagannathan; Sruthi Hundi; Elina Salmela; Patrick Venta; Eva Sarkiala; Tarja Jokinen; Daniela Gorgas; Juha Kere; Pekka Nieminen; Cord Drögemüller; Hannes Lohi

    2016-01-01

    One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined ge...

  15. Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes.

    OpenAIRE

    Hytönen, Marjo K.; Arumilli, Meharji; Lappalainen, Anu K; Owczarek, Marta; Jagannathan, Vidhya; Hundi, Sruthi; Salmela, Elina; Venta, Patrick; Sarkiala, Eva; Jokinen, Tarja; Gorgas, Daniela; Kere, Juha; Nieminen, Pekka; Drögemüller, Cord; Lohi, Hannes

    2016-01-01

    One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined ge...

  16. Molecular Mechanisms of White Spot Syndrome Virus Infection and Perspectives on Treatments.

    Science.gov (United States)

    Verbruggen, Bas; Bickley, Lisa K; van Aerle, Ronny; Bateman, Kelly S; Stentiford, Grant D; Santos, Eduarda M; Tyler, Charles R

    2016-01-01

    Since its emergence in the 1990s, White Spot Disease (WSD) has had major economic and societal impact in the crustacean aquaculture sector. Over the years shrimp farming alone has experienced billion dollar losses through WSD. The disease is caused by the White Spot Syndrome Virus (WSSV), a large dsDNA virus and the only member of the Nimaviridae family. Susceptibility to WSSV in a wide range of crustacean hosts makes it a major risk factor in the translocation of live animals and in commodity products. Currently there are no effective treatments for this disease. Understanding the molecular basis of disease processes has contributed significantly to the treatment of many human and animal pathogens, and with a similar aim considerable efforts have been directed towards understanding host-pathogen molecular interactions for WSD. Work on the molecular mechanisms of pathogenesis in aquatic crustaceans has been restricted by a lack of sequenced and annotated genomes for host species. Nevertheless, some of the key host-pathogen interactions have been established: between viral envelope proteins and host cell receptors at initiation of infection, involvement of various immune system pathways in response to WSSV, and the roles of various host and virus miRNAs in mitigation or progression of disease. Despite these advances, many fundamental knowledge gaps remain; for example, the roles of the majority of WSSV proteins are still unknown. In this review we assess current knowledge of how WSSV infects and replicates in its host, and critique strategies for WSD treatment. PMID:26797629

  17. Are microRNAs the Molecular Link Between Metabolic Syndrome and Alzheimer's Disease?

    Science.gov (United States)

    Codocedo, Juan F; Ríos, Juvenal A; Godoy, Juan A; Inestrosa, Nibaldo C

    2016-05-01

    Alzheimer's disease (AD) is the most common cause of dementia in people over 65 years of age. At present, treatment options for AD address only its symptoms, and there are no available treatments for the prevention or delay of the disease process. Several preclinical and epidemiological studies have linked metabolic risk factors such as hypertension, obesity, dyslipidemia, and diabetes to the pathogenesis of AD. However, the molecular mechanisms that underlie this relationship are not fully understood. Considering that less than 1 % of cases of AD are attributable to genetic factors, the identification of new molecular targets linking metabolic risk factors to neuropathological processes is necessary for improving the diagnosis and treatment of AD. The dysregulation of microRNAs (miRNAs), small non-coding RNAs that regulate several biological processes, has been implicated in the development of different pathologies. In this review, we summarize some of the relevant evidence that points to the role of miRNAs in metabolic syndrome (MetS) and AD and propose that miRNAs may be a molecular link in the complex relationship between both diseases. PMID:25976367

  18. Molecular Mechanisms of White Spot Syndrome Virus Infection and Perspectives on Treatments

    Directory of Open Access Journals (Sweden)

    Bas Verbruggen

    2016-01-01

    Full Text Available Since its emergence in the 1990s, White Spot Disease (WSD has had major economic and societal impact in the crustacean aquaculture sector. Over the years shrimp farming alone has experienced billion dollar losses through WSD. The disease is caused by the White Spot Syndrome Virus (WSSV, a large dsDNA virus and the only member of the Nimaviridae family. Susceptibility to WSSV in a wide range of crustacean hosts makes it a major risk factor in the translocation of live animals and in commodity products. Currently there are no effective treatments for this disease. Understanding the molecular basis of disease processes has contributed significantly to the treatment of many human and animal pathogens, and with a similar aim considerable efforts have been directed towards understanding host–pathogen molecular interactions for WSD. Work on the molecular mechanisms of pathogenesis in aquatic crustaceans has been restricted by a lack of sequenced and annotated genomes for host species. Nevertheless, some of the key host–pathogen interactions have been established: between viral envelope proteins and host cell receptors at initiation of infection, involvement of various immune system pathways in response to WSSV, and the roles of various host and virus miRNAs in mitigation or progression of disease. Despite these advances, many fundamental knowledge gaps remain; for example, the roles of the majority of WSSV proteins are still unknown. In this review we assess current knowledge of how WSSV infects and replicates in its host, and critique strategies for WSD treatment.

  19. Genetic analysis of Tunisian families with Usher syndrome type 1: toward improving early molecular diagnosis

    Science.gov (United States)

    Ben-Rebeh, Imen; Bonnet, Crystel; Bouassida, Walid; Hadjamor, Imen; Ayadi, Hammadi; Ghorbel, Abdelmonem; Petit, Christine; Masmoudi, Saber

    2016-01-01

    Purpose Usher syndrome accounts for about 50% of all hereditary deaf-blindness cases. The most severe form of this syndrome, Usher syndrome type I (USH1), is characterized by profound congenital sensorineural deafness, vestibular dysfunction, and retinitis pigmentosa. Six USH1 genes have been identified, MYO7A, CDH23, PCDH15, USH1C, SANS, and CIB2, encoding myosin VIIA, cadherin-23, protocadherin-15, harmonin, scaffold protein containing ankyrin repeats and a sterile alpha motif (SAM) domain, and calcium- and integrin-binding member 2, respectively. Methods In the present study, we recruited four Tunisian families with a diagnosis of USH1, together with healthy unrelated controls. Affected members underwent detailed audiologic and ocular examinations. We used the North African Deafness (NADf) chip to search for known North African mutations associated with USH. Then, we selected microsatellite markers covering USH1 known loci to genotype the DNA samples. Finally, we performed DNA sequencing of three known USH1 genes: MYO7A, PCDH15, and USH1C. Results Four biallelic mutations, all single base changes, were found in the MYO7A, USH1C, and PCDH15 genes. These mutations consist of a previously reported splicing defect c.470+1G>A in MYO7A, three novel variants, including two nonsense (p.Arg3X and p.Arg134X) in USH1C and PCDH15, respectively, and one frameshift (p.Lys615Asnfs*6) in MYO7A. Conclusions We found a remarkable genetic heterogeneity in the studied families with USH1 with a variety of mutations, among which three were novel. These novel mutations will be included in the NADf mutation screening chip that will allow a higher diagnosis efficiency of this extremely genetically heterogeneous disease. Ultimately, efficient molecular diagnosis of USH in a patient’s early childhood is of utmost importance, allowing better educational and therapeutic management. PMID:27440999

  20. Molecular basis for the Kallmann syndrome-linked fibroblast growth factor receptor mutation

    Energy Technology Data Exchange (ETDEWEB)

    Thurman, Ryan D.; Kathir, Karuppanan Muthusamy; Rajalingam, Dakshinamurthy [Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701 (United States); Kumar, Thallapuranam K. Suresh, E-mail: sthalla@uark.edu [Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701 (United States)

    2012-08-31

    Highlights: Black-Right-Pointing-Pointer The structural basis of the Kallmann syndrome is elucidated. Black-Right-Pointing-Pointer Kallmann syndrome mutation (A168S) induces a subtle conformational change(s). Black-Right-Pointing-Pointer Structural interactions mediated by beta-sheet G are most perturbed. Black-Right-Pointing-Pointer Ligand (FGF)-receptor interaction(s) is completely abolished by Kallmann mutation. Black-Right-Pointing-Pointer Kallmann mutation directly affects the FGF signaling process. -- Abstract: Kallmann syndrome (KS) is a developmental disease that expresses in patients as hypogonadotropic hypogonadism and anosmia. KS is commonly associated with mutations in the extracellular D2 domain of the fibroblast growth factor receptor (FGFR). In this study, for the first time, the molecular basis for the FGFR associated KS mutation (A168S) is elucidated using a variety of biophysical experiments, including multidimensional NMR spectroscopy. Secondary and tertiary structural analysis using far UV circular dichroism, fluorescence and limited trypsin digestion assays suggest that the KS mutation induces subtle tertiary structure change in the D2 domain of FGFR. Results of isothermal titration calorimetry experiments show the KS mutation causes a 10-fold decrease in heparin binding affinity and also a complete loss in ligand (FGF-1) binding. {sup 1}H-{sup 15}N chemical perturbation data suggest that complete loss in the ligand (FGF) binding affinity is triggered by a subtle conformational change that disrupts crucial structural interactions in both the heparin and the FGF binding sites in the D2 domain of FGFR. The novel findings reported in this study are expected to provide valuable clues toward a complete understanding of the other genetic diseases linked to mutations in the FGFR.

  1. Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: Relevance to ocular dysgenesis and hearing impairment

    Directory of Open Access Journals (Sweden)

    Ritch Robert

    2004-06-01

    Full Text Available Abstract Background Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. Methods We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. Results Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1 probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. Conclusions Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss.

  2. [Syndrome Leigh caused by mutations in the SURF1 gene: clinical and molecular-genetic characteristics].

    Science.gov (United States)

    Tsygankova, P G; Mikhaĭlova, S V; Zakharova, E Iu; Pichkur, N A; Il'ina, E S; Nikolaeva, E A; Rudenskaia, G E; Dadali, E L; Kolpakchi, L M; Fedoniuk, I D; Matiushchenko, G N

    2010-01-01

    Syndrome Leigh (SL) or subacute necrotizing encephalomyelopathy - is a rare hereditary genetically heterogeneous disease from the group of mitochondrial encephalomyopathies. Twenty-seven children with SL were examined using clinical, laboratory (measuring lactate levels), MRI and molecular-genetic (polymerase chain reaction genotyping of 9 exons of the SURF1 gene) studies. The mean age of manifestation was 11,6 months. The main manifestations of SL were: delay of psychomotor development, diffuse muscle hypertonic, cerebellar syndrome, ophthalmoparesis, hypertrichosis. The disease had a progressive course with the loss of acquired skills. The blood lactate concentration was increased on average up to 3,1 mM/ml (from 1,9 to 5,1 mM/ml) compared to normal values (1,8 mM/ml). Brain MRI revealed the subcortical and cortical atrophy (80% of cases), symmetrical distinctly delineated hyperintense lesions on T2-weighted images (demyelization) in the basal ganglia and the brain stem (50%), as well as in the cerebellum (25%). Genotyping identified 7 different mutations. The most frequent (64,8%) was the deletion of 2 nucleotides (845delCT) in exon 8 that was in line with early data of Polish researchers thus indicating the Slavic origin of this mutation. Other mutations (574-575insCTGT, 311-321del10insAT and IVS8-1G>) were also frequent in the Russian population. PMID:20436434

  3. The relationship between irritable bowel syndrome and psychiatric disorders: from molecular changes to clinical manifestations.

    Science.gov (United States)

    Fadgyas-Stanculete, Mihaela; Buga, Ana-Maria; Popa-Wagner, Aurel; Dumitrascu, Dan L

    2014-01-01

    Irritable bowel syndrome (IBS) is a functional syndrome characterized by chronic abdominal pain accompanied by altered bowel habits. Although generally considered a functional disorder, there is now substantial evidence that IBS is associated with a poor quality of life and significant negative impact on work and social domains. Neuroimaging studies documented changes in the prefrontal cortex, ventro-lateral and posterior parietal cortex and thalami, and implicate alteration of brain circuits involved in attention, emotion and pain modulation. Emerging data reveals the interaction between psychiatric disorders including generalized anxiety disorder, panic disorder, major depressive disorder, bipolar disorder, and schizophrenia and IBS, which suggests that this association should not be ignored when developing strategies for screening and treatment. Psychological, social and genetic factors appear to be important in the development of IBS symptomatology through several mechanisms: alteration of HPA axis modulation, enhanced perception of visceral stimuli or psychological vulnerability. Elucidating the molecular mechanisms of IBS with or without psychiatric comorbidities is crucial for elucidating the pathophysiology and for the identification of new therapeutical targets in IBS. PMID:25408914

  4. Chromosomal Instability and Molecular Defects in Induced Pluripotent Stem Cells from Nijmegen Breakage Syndrome Patients.

    Science.gov (United States)

    Halevy, Tomer; Akov, Shira; Bohndorf, Martina; Mlody, Barbara; Adjaye, James; Benvenisty, Nissim; Goldberg, Michal

    2016-08-30

    Nijmegen breakage syndrome (NBS) results from the absence of the NBS1 protein, responsible for detection of DNA double-strand breaks (DSBs). NBS is characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. Here, we show successful reprogramming of NBS fibroblasts into induced pluripotent stem cells (NBS-iPSCs). Our data suggest a strong selection for karyotypically normal fibroblasts to go through the reprogramming process. NBS-iPSCs then acquire numerous chromosomal aberrations and show a delayed response to DSB induction. Furthermore, NBS-iPSCs display slower growth, mitotic inhibition, a reduced apoptotic response to stress, and abnormal cell-cycle-related gene expression. Importantly, NBS neural progenitor cells (NBS-NPCs) show downregulation of neural developmental genes, which seems to be mediated by P53. Our results demonstrate the importance of NBS1 in early human development, shed light on the molecular mechanisms underlying this severe syndrome, and further expand our knowledge of the genomic stress cells experience during the reprogramming process. PMID:27545893

  5. Phenotypic and Molecular Convergence of 2q23.1 Deletion Syndrome with Other Neurodevelopmental Syndromes Associated with Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Sureni V. Mullegama

    2015-04-01

    Full Text Available Roughly 20% of autism spectrum disorders (ASD are syndromic with a well-established genetic cause. Studying the genes involved can provide insight into the molecular and cellular mechanisms of ASD. 2q23.1 deletion syndrome (causative gene, MBD5 is a recently identified genetic neurodevelopmental disorder associated with ASD. Mutations in MBD5 have been found in ASD cohorts. In this study, we provide a phenotypic update on the prevalent features of 2q23.1 deletion syndrome, which include severe intellectual disability, seizures, significant speech impairment, sleep disturbance, and autistic-like behavioral problems. Next, we examined the phenotypic, molecular, and network/pathway relationships between nine neurodevelopmental disorders associated with ASD: 2q23.1 deletion Rett, Angelman, Pitt-Hopkins, 2q23.1 duplication, 5q14.3 deletion, Kleefstra, Kabuki make-up, and Smith-Magenis syndromes. We show phenotypic overlaps consisting of intellectual disability, speech delay, seizures, sleep disturbance, hypotonia, and autistic-like behaviors. Molecularly, MBD5 possibly regulates the expression of UBE3A, TCF4, MEF2C, EHMT1 and RAI1. Network analysis reveals that there could be indirect protein interactions, further implicating function for these genes in common pathways. Further, we show that when MBD5 and RAI1 are haploinsufficient, they perturb several common pathways that are linked to neuronal and behavioral development. These findings support further investigations into the molecular and pathway relationships among genes linked to neurodevelopmental disorders and ASD, which will hopefully lead to common points of regulation that may be targeted toward therapeutic intervention.

  6. Molecular evidence of Ureaplasma urealyticum and Ureaplasma parvum colonization in preterm infants during respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Germani Rossella

    2006-11-01

    Full Text Available Abstract Background Ureaplasma urealyticum and U. parvum have been associated with respiratory diseases in premature newborns, but their role in the pathogenesis of the respiratory distress syndrome (RDS is unclear. The aim of this study was to detect, using molecular techniques, the role of Mycoplasma spp. and Ureaplasma spp. in respiratory secretion and blood specimens of preterm newborns with or without RDS and to evaluate the prevalence of perinatal U. urealyticum or U. parvum infection. The influence of chemotherapy on the clinical course was also evaluated. Methods Tracheal aspirate or nasopharingeal fluid samples from 50 preterm babies with (24 or without RDS (26 were analysed for detection of U. urealyticum and U. parvum by culture identification assay and PCR. Sequencing analysis of amplicons allowed us to verify the specificity of methods. Clarithromycin (10 mg kg-1 twice a day was administered in ureaplasma-positive patients who presented clinical signs of RDS. Results 15/24 neonates with RDS (p U. urealyticum or U. parvum. Culture identification assay was positive in 5/50 newborns, three of which with RDS. Sequencing analyses confirmed the specificity of these methods. Association of patent ductus arteriosus with ureaplasma colonization was more statistically significant (p = 0.0004 in patients with RDS than in those without RDS. Conclusion Colonization of the lower respiratory tract by Ureaplasma spp. and particularly by U. parvum in preterm newborns was related to RDS. The routine use of molecular methods could be useful to screen candidate babies for etiologic therapy.

  7. Clinical spectrum and molecular diagnosis of Angelman and Prader-Willi syndrome patients with an imprinting mutation

    Energy Technology Data Exchange (ETDEWEB)

    Saitoh, S.; Cassidy, S.B.; Conroy, J.M. [Univ. of Hospitals of Cleveland, OH (United States)] [and others

    1997-01-20

    Recent studies have identified a new class of Prader-Willi syndrome (PWS) and Angelman syndrome (AS) patients who have biparental inheritance, but neither the typical deletion nor uniparental disomy (UPD) or translocation. However, these patients have uniparental DNA methylation throughout 15q11-q13, and thus appear to have a mutation in the imprinting process for this region. Here we describe detailed clinical findings of five AS imprinting mutation patients (three families) and two PWS imprinting mutation patients (one new family). All these patients have essentially the classical clinical phenotype for the respective syndrome, except that the incidence of microcephaly is lower in imprinting mutation AS patients than in deletion AS patients. Furthermore, imprinting mutation AS and PWS patients do not typically have hypopigmentation, which is commonly found in patients with the usual large deletion. Molecular diagnosis of these cases is initially achieved by DNA methylation analyses of the DN34/ZNF127, PW71 (D15S63), and SNRPN loci. The latter two probes have clear advantages in the simple molecular diagnostic analysis of PWS and AS patients with an imprinting mutation, as has been found for typical deletion or UPD PWS and AS cases. With the recent finding of inherited microdeletions in PWS and AS imprinting mutation families, our studies define a new class of these two syndromes. The clinical and molecular identification of these PWS and AS patients has important genetic counseling consequences. 49 refs., 4 figs., 3 tabs.

  8. Prenatal molecular testing for Beckwith-Wiedemann and Silver-Russell syndromes: a challenge for molecular analysis and genetic counseling.

    Science.gov (United States)

    Eggermann, Thomas; Brioude, Frédéric; Russo, Silvia; Lombardi, Maria P; Bliek, Jet; Maher, Eamonn R; Larizza, Lidia; Prawitt, Dirk; Netchine, Irène; Gonzales, Marie; Grønskov, Karen; Tümer, Zeynep; Monk, David; Mannens, Marcel; Chrzanowska, Krystyna; Walasek, Malgorzata K; Begemann, Matthias; Soellner, Lukas; Eggermann, Katja; Tenorio, Jair; Nevado, Julián; Moore, Gudrun E; Mackay, Deborah Jg; Temple, Karen; Gillessen-Kaesbach, Gabriele; Ogata, Tsutomu; Weksberg, Rosanna; Algar, Elizabeth; Lapunzina, Pablo

    2016-06-01

    Beckwith-Wiedemann and Silver-Russell syndromes (BWS/SRS) are two imprinting disorders (IDs) associated with disturbances of the 11p15.5 chromosomal region. In BWS, epimutations and genomic alterations within 11p15.5 are observed in >70% of patients, whereas in SRS they are observed in about 60% of the cases. In addition, 10% of the SRS patients carry a maternal uniparental disomy of chromosome 7 11p15.5. There is an increasing demand for prenatal testing of these disorders owing to family history, indicative prenatal ultrasound findings or aberrations involving chromosomes 7 and 11. The complex molecular findings underlying these disorders are a challenge not only for laboratories offering these tests but also for geneticists counseling affected families. The scope of counseling must consider the range of detectable disturbances and their origin, the lack of precise quantitative knowledge concerning the inheritance and recurrence risks for the epigenetic abnormalities, which are hallmarks of these developmental disorders. In this paper, experts in the field of BWS and SRS, including members of the European network of congenital IDs (EUCID.net; www.imprinting-disorders.eu), put together their experience and work in the field of 11p15.5-associated IDs with a focus on prenatal testing. Altogether, prenatal tests of 160 fetuses (122 referred for BWS, 38 for SRS testing) from 5 centers were analyzed and reviewed. We summarize the current knowledge on BWS and SRS with respect to diagnostic testing, the consequences for prenatal genetic testing and counseling and our cumulative experience in dealing with these disorders. PMID:26508573

  9. A comparative analysis of the effectiveness of cytogenetic and molecular genetic methods in the detection of Down syndrome

    OpenAIRE

    Mačkić-Đurović, Mirela; Projić, Petar; Ibrulj, Slavka; Čakar, Jasmina; Marjanović, Damir

    2014-01-01

    The goal of this study was to examine the effectiveness of 6 STR markers application (D21S1435, D21S11, D21S1270, D21S1411, D21S226 and IFNAR) in molecular genetic diagnostics of Down syndrome (DS) and to compare it with cytogenetic method. Testing was performed on 73 children, with the previously cytogenetically confirmed Down syndrome. DNA isolated from the buccal swab was used. Previously mentioned loci located on chromosome 21 were simultaneously amplified using quantitative fluorescence ...

  10. Molecular Etiology of Hereditary Single-Side Deafness: Its Association With Pigmentary Disorders and Waardenburg Syndrome.

    Science.gov (United States)

    Kim, Shin Hye; Kim, Ah Reum; Choi, Hyun Seok; Kim, Min Young; Chun, Eun Hi; Oh, Seung-Ha; Choi, Byung Yoon

    2015-10-01

    Unilateral sensorineural hearing loss (USNHL)/single-side deafness (SSD) is a frequently encountered disability in children. The etiology of a substantial portion of USNHL/SSD still remains unknown, and genetic causes have not been clearly elucidated. In this study, the authors evaluated the heritability of USNHL/SSD.The authors sequentially recruited 50 unrelated children with SSD. For an etiologic diagnosis, we performed a rigorous review on the phenotypes of family members of all children and conducted, if necessary, molecular genetic tests including targeted exome sequencing of 129 deafness genes.Among the 50 SSD children cohort, the authors identify 4 (8%) unrelated SSD probands from 4 families (SH136, SB173, SB177, and SB199) with another hearing impaired family members. Notably, all 4 probands in our cohort with a familial history of SSD also have pigmentary abnormalities such as brown freckles or premature gray hair within first degree relatives, which may indicate that genes whose products are involved with pigmentary disorder could be candidates for heritable SSD. Indeed, SH136 and SB199 turned out to segregate a mutation in MITF and PAX3, respectively, leading to a molecular diagnosis of Waardenburg syndrome (WS).We report, for the first time in the literature, a significant heritability of pediatric SSD. There is a strong association between the heritability of USNHL/SSD and the pigmentary abnormality, shedding a new light on the understanding of the molecular basis of heritable USNHL/SSD. In case of children with congenital SSD, it would be mandatory to rigorously screen pigmentary abnormalities. WS should also be included in the differential diagnosis of children with USNHL/SSD, especially in a familial form. PMID:26512583

  11. Fragile X Syndrome: Keys to the Molecular Genetics of Synaptic Plasticity

    Science.gov (United States)

    Lombroso, Paul J.; Ogren, Marilee P.

    2008-01-01

    Fragile X syndrome, the most common form of inherited mental retardation is discussed. The relationship between specific impairments in synaptic plasticity and Fragile X syndrome is investigated as it strengthens synaptic contacts between neurons.

  12. Jacobsen Syndrome: Surgical Complications due to Unsuspected Diagnosis, the Importance of Molecular Studies in Patients with Craniosynostosis.

    Science.gov (United States)

    Linares Chávez, Etzalli P; Toral López, Jaime; Valdés Miranda, Juan M; González Huerta, Luz M; Perez Cabrera, Adrian; Del Refugio Rivera Vega, María; Messina Baas, Olga M; Cuevas-Covarrubias, Sergio A

    2016-02-01

    Jacobsen syndrome (JBS) is an uncommon contiguous gene syndrome. About 85-92% of cases have a de novo origin. Clinical variability and severity probably depend on the size of the affected region. The typical clinical features in JBS include intellectual disability, growth retardation, craniofacial dysmorphism as well as craniosynostosis, congenital heart disease, and platelet abnormalities. The proband was a 1 year/3-month-old Mexican male. Oligonucleotide-SNP array analysis using the GeneChip Human Cytoscan HD was carried out for the patient from genomic DNA. The SNP array showed a 14.2-Mb deletion in chromosome 11q23.3q25 (120,706-134,938 Mb), which involved 163 RefSeq genes in the database of genomic variation. We report a novel deletion in JBS that increases the knowledge of the variability in the mutation sites in this region and expands the spectrum of molecular and clinical defects in this syndrome. PMID:26997943

  13. Jacobsen Syndrome: Surgical Complications due to Unsuspected Diagnosis, the Importance of Molecular Studies in Patients with Craniosynostosis

    Science.gov (United States)

    Linares Chávez, Etzalli P.; Toral López, Jaime; Valdés Miranda, Juan M.; González Huerta, Luz M.; Perez Cabrera, Adrian; del Refugio Rivera Vega, María; Messina Baas, Olga M.; Cuevas-Covarrubias, Sergio A.

    2016-01-01

    Jacobsen syndrome (JBS) is an uncommon contiguous gene syndrome. About 85-92% of cases have a de novo origin. Clinical variability and severity probably depend on the size of the affected region. The typical clinical features in JBS include intellectual disability, growth retardation, craniofacial dysmorphism as well as craniosynostosis, congenital heart disease, and platelet abnormalities. The proband was a 1 year/3-month-old Mexican male. Oligonucleotide-SNP array analysis using the GeneChip Human Cytoscan HD was carried out for the patient from genomic DNA. The SNP array showed a 14.2-Mb deletion in chromosome 11q23.3q25 (120,706-134,938 Mb), which involved 163 RefSeq genes in the database of genomic variation. We report a novel deletion in JBS that increases the knowledge of the variability in the mutation sites in this region and expands the spectrum of molecular and clinical defects in this syndrome. PMID:26997943

  14. Spectrum of novel mutations found in Waardenburg syndrome types 1 and 2: implications for molecular genetic diagnostics

    OpenAIRE

    Wildhardt, Gabriele; Zirn, Birgit; Graul-Neumann, Luitgard M; Wechtenbruch, Juliane; Suckfuell, Markus; Buske, Annegret; Bohring, Axel; Kubisch, Christian; Vogt, Stefanie; Strobl-Wildemann, Gertrud; Greally, Marie; Bartsch, Oliver; Steinberger, Daniela

    2013-01-01

    Objectives: Till date, mutations in the genes PAX3 and MITF have been described in Waardenburg syndrome (WS), which is clinically characterised by congenital hearing loss and pigmentation anomalies. Our study intended to determine the frequency of mutations and deletions in these genes, to assess the clinical phenotype in detail and to identify rational priorities for molecular genetic diagnostics procedures. Design: Prospective analysis. Patients: 19 Caucasian patients with typical features ...

  15. Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes

    Science.gov (United States)

    Hytönen, Marjo K.; Arumilli, Meharji; Lappalainen, Anu K.; Owczarek-Lipska, Marta; Jagannathan, Vidhya; Hundi, Sruthi; Salmela, Elina; Venta, Patrick; Sarkiala, Eva; Jokinen, Tarja; Gorgas, Daniela; Kere, Juha; Nieminen, Pekka

    2016-01-01

    One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively. CMO is a clinical equivalent to an infantile cortical hyperostosis (Caffey disease), for which SLC37A2 is a new candidate gene. SLC37A2 is a poorly characterized member of a glucose-phosphate transporter family without previous disease associations. It is expressed in many tissues, including cells of the macrophage lineage, e.g. osteoclasts, and suggests a disease mechanism, in which an impaired glucose homeostasis in osteoclasts compromises their function in the developing bone, leading to hyperostosis. Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity for the canine conditions. PMID:27187611

  16. Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes.

    Science.gov (United States)

    Hytönen, Marjo K; Arumilli, Meharji; Lappalainen, Anu K; Owczarek-Lipska, Marta; Jagannathan, Vidhya; Hundi, Sruthi; Salmela, Elina; Venta, Patrick; Sarkiala, Eva; Jokinen, Tarja; Gorgas, Daniela; Kere, Juha; Nieminen, Pekka; Drögemüller, Cord; Lohi, Hannes

    2016-05-01

    One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively. CMO is a clinical equivalent to an infantile cortical hyperostosis (Caffey disease), for which SLC37A2 is a new candidate gene. SLC37A2 is a poorly characterized member of a glucose-phosphate transporter family without previous disease associations. It is expressed in many tissues, including cells of the macrophage lineage, e.g. osteoclasts, and suggests a disease mechanism, in which an impaired glucose homeostasis in osteoclasts compromises their function in the developing bone, leading to hyperostosis. Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity for the canine conditions. PMID:27187611

  17. Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes.

    Directory of Open Access Journals (Sweden)

    Marjo K Hytönen

    2016-05-01

    Full Text Available One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO, a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant, SCARF2 (truncating 2-bp deletion and FAM20C (missense variant genes, respectively. CMO is a clinical equivalent to an infantile cortical hyperostosis (Caffey disease, for which SLC37A2 is a new candidate gene. SLC37A2 is a poorly characterized member of a glucose-phosphate transporter family without previous disease associations. It is expressed in many tissues, including cells of the macrophage lineage, e.g. osteoclasts, and suggests a disease mechanism, in which an impaired glucose homeostasis in osteoclasts compromises their function in the developing bone, leading to hyperostosis. Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity for the canine conditions.

  18. Susceptibility to DNA damage as a molecular mechanism for non-syndromic cleft lip and palate.

    Directory of Open Access Journals (Sweden)

    Gerson Shigeru Kobayashi

    Full Text Available Non-syndromic cleft lip/palate (NSCL/P is a complex, frequent congenital malformation, determined by the interplay between genetic and environmental factors during embryonic development. Previous findings have appointed an aetiological overlap between NSCL/P and cancer, and alterations in similar biological pathways may underpin both conditions. Here, using a combination of transcriptomic profiling and functional approaches, we report that NSCL/P dental pulp stem cells exhibit dysregulation of a co-expressed gene network mainly associated with DNA double-strand break repair and cell cycle control (p = 2.88×10(-2-5.02×10(-9. This network included important genes for these cellular processes, such as BRCA1, RAD51, and MSH2, which are predicted to be regulated by transcription factor E2F1. Functional assays support these findings, revealing that NSCL/P cells accumulate DNA double-strand breaks upon exposure to H2O2. Furthermore, we show that E2f1, Brca1 and Rad51 are co-expressed in the developing embryonic orofacial primordia, and may act as a molecular hub playing a role in lip and palate morphogenesis. In conclusion, we show for the first time that cellular defences against DNA damage may take part in determining the susceptibility to NSCL/P. These results are in accordance with the hypothesis of aetiological overlap between this malformation and cancer, and suggest a new pathogenic mechanism for the disease.

  19. Molecular mechanisms regulating impaired neurogenesis of fragile X syndrome human embryonic stem cells.

    Science.gov (United States)

    Telias, Michael; Mayshar, Yoav; Amit, Ami; Ben-Yosef, Dalit

    2015-10-15

    Fragile X syndrome (FXS) is the most common form of inherited cognitive impairment. It is caused by developmental inactivation of the FMR1 gene and the absence of its encoded protein FMRP, which plays pivotal roles in brain development and function. In FXS embryos with full FMR1 mutation, FMRP is expressed during early embryogenesis and is gradually downregulated at the third trimester of pregnancy. FX-human embryonic stem cells (FX-hESCs), derived from FX human blastocysts, demonstrate the same pattern of developmentally regulated FMR1 inactivation when subjected to in vitro neural differentiation (IVND). In this study, we used this in vitro human platform to explore the molecular mechanisms downstream to FMRP in the context of early human embryonic neurogenesis. Our results show a novel role for the SOX superfamily of transcription factors, specifically for SOX2 and SOX9, which could explain the reduced and delayed neurogenesis observed in FX cells. In addition, we assess in this study the "GSK3β theory of FXS" for the first time in a human-based model. We found no evidence for a pathological increase in GSK3β protein levels upon cellular loss of FMRP, in contrast to what was found in the brain of Fmr1 knockout mice. Our study adds novel data on potential downstream targets of FMRP and highlights the importance of the FX-hESC IVND system. PMID:26393806

  20. Cytogenetic and molecular studies of Down syndrome individuals with transient leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Shen, J.J.; Hassold, T.J. [Case Western Reserve Univ., Cleveland, OH (United States); Zipursky, A. [Univ. of Toronto, Ontario (Canada)] [and others

    1994-09-01

    There is an increased risk of leukemia in Down syndrome (DS) patients with estimates ranging from 14 to 30 times the incidence rate observed for normal children. Furthermore, one subtype of leukemia, called transient myeloproliferative disorder, or transient leukemia (TL), occurs almost exclusively in DS infants. The basis of the association between DS and leukemia is unknown but we and others have hypothesized that it may be attributable to the mechanism of origin of the extra chromosome. Therefore, we have initiated a cytogenetic and molecular study of nondisjunction in leukemic DS individuals. To date, we have obtained blood and/or tissue samples from 54 individuals, consisting of 16 cases with TL and 6 with acute megakaryoblastic leukemia (postulated to be related to TL), and 32 cases of other forms of leukemia (15 ALL, 10 AML, 7 others). Our preliminary data suggest significant differences between DS children with TL and those with other types of leukemia or DS individuals with no history of leukemia. For example, the TL cases have a highly significant increase in the frequency of {open_quotes}atypical{close_quotes} constitutional karyotypes (i.e. mosaic trisomies, rings, isochromosomes) and are almost always male. Initial gene mapping studies of these cases aimed at identifying loci important in the genesis of TL will be presented and compared to similar data from DS individuals with other forms of leukemia and those without leukemia.

  1. Cytological and molecular studies of chromosomal radiosensitivity in Down Syndrome cells

    International Nuclear Information System (INIS)

    Molecular, cellular and cytogenetic studies were conducted to determine if altered levels of poly(ADP-ribose) polymerase, a DNA repair-related enzyme, is responsible for the reported formation of excess X-ray induced chromosome aberrations in cells derived from Down Syndrome (DS) patients. Nonstimulated lymphocytes from normal and DS subjects were pretreated with 3-aminobenzamide, an inhibitor of poly(ADP-ribose) polymerase, for 30 minutes before exposure to X-rays and the levels of induced chromosome aberrations were determined in mitotic cells. DS lymphocytes exhibited significantly higher frequencies of chromosome aberrations in the presence of 3-aminobenzamide that normal lymphocytes. No difference was observed in the absence of 3-aminobenzamide. Additional studies were done using normal and DS lymphoblastoid cell lines which exhibited a similar response at the DNA level as the lymphocytes. Analysis of poly(ADP-ribose) polymerase activity based on incorporation of the substrate, NAD+, into acid insoluble materials, revealed that there was no significant difference in the ability to form poly (ADP-ribose) in the DS or normal cells. 3-aminobenzamide effectively inhibited poly(ADP-ribose) polymerase in both the normal and DS cells

  2. Clinical, biochemical and molecular analysis of two infants with familial chylomicronemia syndrome.

    Science.gov (United States)

    Zhang, Yonghong; Zhou, Jing; Zheng, Wenxin; Lan, Zhangzhang; Huang, Zhiwei; Yang, Qingnan; Liu, Chengbo; Gao, Rui; Zhang, Yongjun

    2016-01-01

    Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disease due mainly to inherited deficiencies in the proteins or enzymes involved in the clearance of triglycerides from circulation. It usually happens in late childhood and adolescence, which can have serious consequences if misdiagnosed or untreated. In the present study, we investigated two Chinese male babies (A and B), 30d and 48d in age, respectively, who have milky plasma. Clinical, biochemical, and radiological assessments were performed, while samples from the patients were referred for molecular diagnosis, including genetic testing and subsequent analysis of related genes. The fasting serum lipids of the two patients showed extreme lipid abnormalities. Through a low-lipid formula diet including skimmed milk and dietary advice, their plasma lipid levels were significantly lower and more stable at the time of hospital discharge. The genetic testing revealed compound heterozygote mutations in the lipoprotein lipase (LPL) gene for patient A and two known compound heterozygote LPL gene mutations for the patient B. FCS is the most dramatic example of severe hypertriglyceridemia. Early diagnosis and timely dietary intervention is very important for affected children. PMID:27153815

  3. Trapped neutrophil syndrome in a Border Collie dog: clinical, clinico-pathologic, and molecular findings.

    Science.gov (United States)

    Mizukami, Keijiro; Shoubudani, Tomoaki; Nishimoto, Seira; Kawamura, Ryuta; Yabuki, Akira; Yamato, Osamu

    2012-06-01

    Trapped neutrophil syndrome (TNS) is an autosomal recessive inherited neutropenia known in Border Collies since the 1990's. Recently, the causative mutation has been identified in the canine VPS13B gene and a DNA-based diagnosis has now become available. The present paper describes clinical and clinico-pathologic findings in a Border Collie with TNS that was molecularly diagnosed for the first time in Japan. In a 10-week-old male Border Collie with microgenesis and symptoms related to recurrent infections, a hematological examination revealed severe leukopenia due to neutropenia, suggesting the dog to be affected by inherited neutropenic immunodeficiency. Direct DNA sequencing demonstrated that the dog was homozygous for the causative mutation of TNS and both its parents were heterozygous carriers. In addition, a simple and rapid polymerase chain reaction-based length polymorphism analysis coupled with microchip electrophoresis was developed for the genotyping of TNS. This assay could discriminate clearly all genotypes, suggesting that it was suitable for both individual diagnosis and large-scale surveys for prevention. PMID:22240985

  4. Clinical and Molecular Phenotype of Aicardi-Goutières Syndrome

    Science.gov (United States)

    Rice, Gillian ; Patrick, Teresa ; Parmar, Rekha ; Taylor, Claire F. ; Aeby, Alec ; Aicardi, Jean ; Artuch, Rafael ; Montalto, Simon Attard ; Bacino, Carlos A. ; Barroso, Bruno ; Baxter, Peter ; Benko, Willam S. ; Bergmann, Carsten ; Bertini, Enrico ; Biancheri, Roberta ; Blair, Edward M. ; Blau, Nenad ; Bonthron, David T. ; Briggs, Tracy ; Brueton, Louise A. ; Brunner, Han G. ; Burke, Christopher J. ; Carr, Ian M. ; Carvalho, Daniel R. ; Chandler, Kate E. ; Christen, Hans-Jürgen ; Corry, Peter C. ; Cowan, Frances M. ; Cox, Helen ; D’Arrigo, Stefano ; Dean, John ; De Laet, Corinne ; De Praeter, Claudine ; Déry, Catherine ; Ferrie, Colin D. ; Flintoff, Kim ; Frints, Suzanna G. M. ; Garcia-Cazorla, Angels ; Gener, Blanca ; Goizet, Cyril ; Goutières, Françoise ; Green, Andrew J. ; Guët, Agnès ; Hamel, Ben C. J. ; Hayward, Bruce E. ; Heiberg, Arvid ; Hennekam, Raoul C. ; Husson, Marie ; Jackson, Andrew P. ; Jayatunga, Rasieka ; Jiang, Yong-Hui ; Kant, Sarina G. ; Kao, Amy ; King, Mary D. ; Kingston, Helen M. ; Klepper, Joerg ; van der Knaap, Marjo S. ; Kornberg, Andrew J. ; Kotzot, Dieter ; Kratzer, Wilfried ; Lacombe, Didier ; Lagae, Lieven ; Landrieu, Pierre Georges ; Lanzi, Giovanni ; Leitch, Andrea ; Lim, Ming J. ; Livingston, John H. ; Lourenco, Charles M. ; Lyall, E. G. Hermione ; Lynch, Sally A. ; Lyons, Michael J. ; Marom, Daphna ; McClure, John P. ; McWilliam, Robert ; Melancon, Serge B. ; Mewasingh, Leena D. ; Moutard, Marie-Laure ; Nischal, Ken K. ; Østergaard, John R. ; Prendiville, Julie ; Rasmussen, Magnhild ; Rogers, R. Curtis ; Roland, Dominique ; Rosser, Elisabeth M. ; Rostasy, Kevin ; Roubertie, Agathe ; Sanchis, Amparo ; Schiffmann, Raphael ; Scholl-Bürgi, Sabine ; Seal, Sunita ; Shalev, Stavit A. ; Corcoles, C. Sierra ; Sinha, Gyan P. ; Soler, Doriette ; Spiegel, Ronen ; Stephenson, John B. P. ; Tacke, Uta ; Tan, Tiong Yang ; Till, Marianne ; Tolmie, John L. ; Tomlin, Pam ; Vagnarelli, Federica ; Valente, Enza Maria ; Van Coster, Rudy N. A. ; Van der Aa, Nathalie ; Vanderver, Adeline ; Vles, Johannes S. H. ; Voit, Thomas ; Wassmer, Evangeline ; Weschke, Bernhard ; Whiteford, Margo L. ; Willemsen, Michel A. A. ; Zankl, Andreas ; Zuberi, Sameer M. ; Orcesi, Simona ; Fazzi, Elisa ; Lebon, Pierre ; Crow, Yanick J. 

    2007-01-01

    Aicardi-Goutières syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3′→5′ exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe. Almost all mutations in RNASEH2A, RNASEH2B, and RNASEH2C were missense. We identified an RNASEH2C founder mutation in 13 Pakistani families. We also collected clinical data from 123 mutation-positive patients. Two clinical presentations could be delineated: an early-onset neonatal form, highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later-onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Mortality was correlated with genotype; 34.3% of patients with TREX1, RNASEH2A, and RNASEH2C mutations versus 8.0% RNASEH2B mutation–positive patients were known to have died (P=.001). Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation-screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS-causing gene remains to be identified. PMID:17846997

  5. A de novo germline MLH1 mutation in a Lynch syndrome patient with discordant immunohistochemical and molecular biology test results

    Institute of Scientific and Technical Information of China (English)

    Fabrice Airaud; Sébastien Küry; Isabelle Valo; Ingrid Maury; Dominique Bonneau; Olivier Ingster; Stéphane Bezieau

    2012-01-01

    We describe a patient with a Homo sapiens mutL homolog 1 (MLH1)-associated Lynch syndrome with previous diagnoses of two distinct primary cancers:a sigmoid colon cancer at the age of 39 years,and a right colon cancer at the age of 50 years.The mutation identified in his blood and buccal cells,c.1771delG,p.Asp591Ilefs*25,appears to be a de novo event,as it was not transmitted by either of his parents.This type of de novo event is rare in MLH1 as only three cases have been reported in the literature so far.Furthermore,the discordant results observed between replication error phenotyping and immunohistochemistry highlight the importance of the systematic use of both pre-screening tests in the molecular diagnosis of Lynch syndrome.

  6. Mutations in the codon for a conserved arginine-1563 in the COL4A5 collagen gene in Alport syndrome

    DEFF Research Database (Denmark)

    Zhou, J; Gregory, M C; Hertz, Jens Michael; Barker, D F; Atkin, C; Spencer, E S; Tryggvason, K

    1993-01-01

    arginine to the translation stop codon TGA. In Utah kindred 2123 and in the Danish kindred A13, there was a C-->T mutation in the noncoding strand changing the same codon to CAA for glutamine. Both mutations were confirmed by allele-specific hybridization on PCR-amplified DNA from other family members....

  7. Detection of mutations in the COL4A5 gene by SSCP in X-linked Alport syndrome

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Juncker, I; Persson, U;

    2001-01-01

    , three in-frame deletions, four nonsense mutations, and six splice site mutations. Twenty-two of the mutations have not previously been reported. Furthermore, we found one non-pathogenic amino acid substitution, one rare variant in a non-coding region, and one polymorphism with a heterozygosity of 28......%. Three de novo mutations were found, two of which were paternal and one of maternal origin....

  8. The relationship between irritable bowel syndrome and psychiatric disorders: from molecular changes to clinical manifestations

    OpenAIRE

    Fadgyas-Stanculete, Mihaela; Buga, Ana-Maria; Popa-Wagner, Aurel; Dumitrascu, Dan L

    2014-01-01

    Irritable bowel syndrome (IBS) is a functional syndrome characterized by chronic abdominal pain accompanied by altered bowel habits. Although generally considered a functional disorder, there is now substantial evidence that IBS is associated with a poor quality of life and significant negative impact on work and social domains. Neuroimaging studies documented changes in the prefrontal cortex, ventro-lateral and posterior parietal cortex and thalami, and implicate alteration of brain circuits...

  9. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone

    International Nuclear Information System (INIS)

    The authors considered an infectious molecular clone of acquired immunodeficiency syndrome-associated retrovirus. Upon transfection, this clone directed the production of infectious virus particles in a wide variety of cells in addition to human T4 cells. The progeny, infectious virions, were synthesized in mouse, mink, monkey, and several human non-T cell lines, indicating the absence of any intracellular obstacle to viral RNA or protein production or assembly. During the course of these studies, a human colon carcinoma cell line, exquisitely sensitive to DNA transfection, was identified

  10. Preliminary molecular basis of Danggui-buxue-tang on Qi deficiency and blood stasis syndrome

    Institute of Scientific and Technical Information of China (English)

    LIU Ya; LI Xiao-hui

    2008-01-01

    Objective To study the molecular biology mechanism of Danggui-buxue-tang on tonifying Qi and controlling blood circulation through modulation the immune functional genes. Methods Rats were randomly divided into control group, model group, and Danggui-buxue-tang group. Effect of Dang-guibuxue-tang on mRNA expressions of IL-1β, TNF-α, HSP-70, NF-kB, p38MAPK and JNK in blood cells of rats with Qi deficiency and blood stasis were measured with real-time fluorescent quantitative-PCR at 5th, 14th and 28th day. And that in artery wall were determined at the 28th day. NF-kB/p65 and p-c-jun protein expressions in rat artery wall were detected by western blotting as well. Results In model group, TNF-α, IL-1β, NF-kB, HSP-70, p38MAPK and JNK mRNA expression in blood cell increased significantly compared with control group. Compared with model group, mRNA expression of IL-1βand JNK decreased significantly; TNF-α decreased at 5th, 14th day;HSP-70, p38MAPK decreased at 14th, 28th day; NF-kB decreased at 28th day. In model group, TNF-α, IL-1β, NF-kB, p38MAPK and JNK mRNA expression in artery increased compared with control group, excluded HSP-70, and that in Danggui-buxue-tang group decreased significantly. In model group, NF-kB/p65 and p-c-jun protein expression in artery increased compared with control group, and that in Danggui-buxue-tang group decreased significantly. Conclusions The effects of Dang-guibuxuetang on Qi deficiency and blood stasis syndrome was brought from the regulating of cytokine network at multi-link and multi-target, NF-kB, p38MAPK and JNK signal transduction pathways included. Through which the immune system and whole body reached to a functional balance status.

  11. The first Korean case of HDR syndrome confirmed by clinical and molecular investigation.

    Science.gov (United States)

    Cheon, Chong Kun; Kim, Gu Hwan; Yoo, Han Wook

    2015-01-01

    Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is a rare condition inherited as autosomal dominant trait and characterized by hypoparathyroidism, sensorineural deafness, and renal dysplasia. HDR syndrome is caused by haploinsufficiency of the GATA3 gene located on chromosome 10p15. Here, we report the case of a 32-day-old Korean male with HDR syndrome. He was presented due to repeated seizures over previous 3 days. The patient was born after 40 weeks of gestation with birth weight of 2930 g, and was the first-born baby of healthy Korean parents. Hypoparathyroidism was first noticed due to seizure. A multicystic left dysplastic kidney and vesicoureteral reflux were detected by ultrasound after birth. Auditory brainstem response (ABR) testing revealed that the patient had moderate sensorineural deafness, with hearing losses of 80 dB at the mid and higher frequencies for both ears. Echocardiography finding revealed secundum atrial septal deftect. Based on biochemical results and clinical findings, a presumptive diagnosis of HDR syndrome was made. GATA3 mutation analysis identified a heterozygous deletion, c.153del (p.Phe51Leufs*144) in exon 1 causing a frameshift mutation, which is a novel de novo mutation. Therefore, we suggest that HDR syndrome should be considered in the differential diagnosis in symptomatic or asymptomatic patients with hypoparathyroidism, and that renal ultrasound or ABR testing be performed to prevent a missed diagnosis. This is the first report on Korean patient with confirmed HDR syndrome with novel mutation. PMID:25510779

  12. A genetic and molecular update on adrenocortical causes of Cushing syndrome.

    Science.gov (United States)

    Lodish, Maya; Stratakis, Constantine A

    2016-05-01

    Primary adrenal Cushing syndrome is the result of cortisol hypersecretion mainly by adenomas and, rarely, by bilateral micronodular or macronodular adrenocortical hyperplasia. cAMP-dependent protein kinase A (PKA) signalling is the major activator of cortisol secretion in the adrenal cortex. Many adenomas and hyperplasias associated with primary hypercortisolism carry somatic or germline mutations in genes that encode constituents of the cAMP-PKA pathway. In this Review, we discuss Cushing syndrome and its linkage to dysregulated cAMP-PKA signalling, with a focus on genetic findings in the past few years. In addition, we discuss the presence of germline inactivating mutations in ARMC5 in patients with primary bilateral macronodular adrenocortical hyperplasia. This finding has implications for genetic counselling of affected patients; hitherto, most patients with this form of adrenal hyperplasia and Cushing syndrome were thought to have a sporadic and not a familial disorder. PMID:26965378

  13. The molecular mechanism underlying Roberts syndrome involves loss of ESCO2 acetyltransferase activity

    DEFF Research Database (Denmark)

    Gordillo, M.; Vega, H.; Trainer, A.H.;

    2008-01-01

    Roberts syndrome/SC phocomelia (RBS) is an autosomal recessive disorder with growth retardation, craniofacial abnormalities and limb reduction. Cellular alterations in RBS include lack of cohesion at the heterochromatic regions around centromeres and the long arm of the Y chromosome, reduced grow...

  14. Scientific statement on the diagnostic criteria, epidemiology, pathophysiology, and molecular genetics of polycystic ovary syndrome

    NARCIS (Netherlands)

    D. Dumesic (Daniel); S.E. Oberfield (Sharon E.); E. Stener-Victorin (Elisabet); J.C. Marshall (John C.); J.S.E. Laven (Joop); R.S. Legro (Richard)

    2015-01-01

    textabstractPolycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has both adverse reproductive and metabolic implications for affected women. However, there is generally poor understanding of its etiology. Varying expert-based diagnostic criteria utilize some combination of

  15. White spot syndrome virus molecular epidemiology: relation with shrimp farming and disease outbreaks

    NARCIS (Netherlands)

    Tran Thi Tuyet, H.

    2012-01-01

    White spot syndrome virus (WSSV), the causative agent of white spot disease (WSD), has been responsible for most shrimp production losses around the world since the early 1990s. Previous research has focused mainly on the characterization of WSSV genomic variation to gain a better insight in the evo

  16. A molecular analysis of fecal and mucosal bacterial communities in irritable bowel syndrome.

    LENUS (Irish Health Repository)

    Codling, Caroline

    2010-02-01

    The objectives of this study were, firstly, to determine the diversity of the host\\'s gut microbiota in irritable bowel syndrome (IBS) using a culture-independent method (DGGE of the 16S rRNA gene) and, secondly, to examine mucosal biopsies of IBS patients and compare them to their own fecal microbiota.

  17. Arterial tortuosity syndrome : Clinical and molecular findings in 12 newly identified families

    NARCIS (Netherlands)

    Callewaert, B. L.; Willaert, A.; Kerstjens-Frederikse, W. S.; De Backer, J.; Devriendt, K.; Albrecht, B.; Ramos-Arroyo, M. A.; Doco-Fenzy, M.; Hennekam, R. C. M.; Pyeritz, R. E.; Krogmann, O. N.; Gillessen-kaesbach, G.; Wakeling, E. L.; Nik-zainal, S.; Francannet, C.; Mauran, P.; Booth, C.; Barrow, M.; Dekens, R.; Loeys, B. L.; Coucke, P. J.; De Paepe, A. M.

    2008-01-01

    Arterial tortuosity syndrome (ATS) is a rare autosomal recessive connective tissue disease, characterized by widespread arterial involvement with elongation, tortuosity, and aneurysms of the large and middle-sized arteries. Recently, SLC2A10 mutations were identified in this condition. This gene enc

  18. Phenotypic variability of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA: clinical, molecular and biochemical delineation

    Directory of Open Access Journals (Sweden)

    Kariminejad Ariana

    2011-06-01

    Full Text Available Abstract Background The kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA (OMIM 225400 is a rare inheritable connective tissue disorder characterized by a deficiency of collagen lysyl hydroxylase 1 (LH1; EC 1.14.11.4 due to mutations in PLOD1. Biochemically this results in underhydroxylation of collagen lysyl residues and, hence, an abnormal pattern of lysyl pyridinoline (LP and hydroxylysyl pyridinoline (HP crosslinks excreted in the urine. Clinically the disorder is characterized by hypotonia and kyphoscoliosis at birth, joint hypermobility, and skin hyperelasticity and fragility. Severe hypotonia usually leads to delay in gross motor development, whereas cognitive development is reported to be normal. Methods We describe the clinical, biochemical and molecular characterisation, as well as electron microscopy findings of skin, in 15 patients newly diagnosed with this rare type of Ehlers-Danlos syndrome. Results Age at diagnosis ranged from 5 months to 27 years, with only 1/3 of the patients been diagnosed correctly in the first year of life. A similar disease frequency was found in females and males, however a broad disease severity spectrum (intra- and interfamilial, independent of molecular background or biochemical phenotype, was observed. Kyphoscoliosis, one of the main clinical features was not present at birth in 4 patients. Importantly we also noted the occurrence of vascular rupture antenatally and postnatally, as well as developmental delay in 5 patients. Conclusion In view of these findings we propose that EDS VIA is a highly variable clinical entity, presenting with a broad clinical spectrum, which may also be associated with cognitive delay and an increased risk for vascular events. Genotype/phenotype association studies and additional molecular investigations in more extended EDS VIA populations will be necessary to further elucidate the cause of the variability of the disease severity.

  19. [Mitochondrial diseases in children including Leigh syndrome--biochemical and molecular background].

    Science.gov (United States)

    Pronicka, Ewa; Piekutowska-Abramczuk, Dorota; Pronicki, Maciej

    2008-01-01

    Mitochondrial diseases in children are more frequently caused by mutations in nuclear DNA then in mtDNA. Special clinical phenotypes are associated with the mutations in SURF1 gene, in SCO2 gene and with mtDNA depletion syndromes. Leigh syndrome is the most common clinical presentation of various mitochondrial disorders during childhood. Elevation of lactate in blood, cerebrospinal fluid and urine is a simple biochemical marker of mitochondrial disorders but its specificity and sensitivity are low. Biochemical investigation of muscle biopsy and search for mitochondrial mutations remain a gold standard in the diagnosis. The standarized diagnostic criteria to establish level of diagnostic certainty (possible, probable, definite) are proposed to be used in practice; these include clinical features, neuroimaging and muscle biopsy investigations. Further research directions to improve our understanding of mitochondrial pathologies in children are suggested. PMID:18807927

  20. Molecular findings of Colombian patients with type VI mucopolysaccharidosis (Maroteaux–Lamy syndrome)

    OpenAIRE

    Gustavo Adolfo Giraldo; Paola Ayala-Ramírez; Juan Carlos Prieto; Reggie García-Robles; Johanna Carolina Acosta

    2016-01-01

    Introduction Maroteaux–Lamy syndrome, or mucopolysaccharidosis (MPS) type VI, is an autosomal recessive lysosomal storage disease caused by a deficient activity of the enzyme arylsulfatase B (ARSB), required to degrade dermatan sulfate. The onset and progression of the disease vary, producing a spectrum of clinical presentation. So far, 133 mutations have been reported. The aim of this study is to determine the mutations in the ARSB gene that are responsible for this disease in Colombian pati...

  1. [Conception for permanent activation of nuclear factor kbeta as molecular basis for metabolic syndrom pathogenesis].

    Science.gov (United States)

    Kaidashev, I P

    2013-01-01

    The analysis of new data concerning the development of pathology due to the community of evolutionary new pathological factors was done. Author provides the comparison of well-known and new definition for "metabolic syndrome" and diagnostic criteria of this pathology. The conception for permanent activation of nuclear factor kbeta as possible typic pathological process was discussed. Suppose that NF-kbeta is the possible key molecule in the initiation and formation of "vicious circle"--insulinresistance--inflammation--atherosclerosis. PMID:24340624

  2. Ventilator-Induced Lung Injury (VILI) in Acute Respiratory Distress Syndrome (ARDS): Volutrauma and Molecular Effects

    OpenAIRE

    Carrasco Loza, R; Villamizar Rodríguez, G; Medel Fernández, N

    2015-01-01

    Acute Respiratory Distress Syndrome (ARDS) is a clinical condition secondary to a variety of insults leading to a severe acute respiratory failure and high mortality in critically ill patients. Patients with ARDS generally require mechanical ventilation, which is another important factor that may increase the ALI (acute lung injury) by a series of pathophysiological mechanisms, whose common element is the initial volutrauma in the alveolar units, and forming part of an entity known clinically...

  3. Altered molecular specificity of surfactant phosphatidycholine synthesis in patients with acute respiratory distress syndrome

    OpenAIRE

    Dushianthan, Ahilanandan; Goss, Victoria; Cusack, Rebecca; Grocott, Michael P. W.; Postle, Anthony D

    2014-01-01

    Background Acute respiratory distress syndrome (ARDS) is a life-threatening critical illness, characterised by qualitative and quantitative surfactant compositional changes associated with premature airway collapse, gas-exchange abnormalities and acute hypoxic respiratory failure. The underlying mechanisms for this dysregulation in surfactant metabolisms are not fully explored. Lack of therapeutic benefits from clinical trials, highlight the importance of detailed in-vivo analysis and charact...

  4. Molecular mechanisms of atherosclerosis in metabolic syndrome: role of reduced IRS2-dependent signaling

    OpenAIRE

    González-Navarro, Herminia; Vinué, Ángela; Vila-Caballer, Marian; Fortuño, Ana; Beloqui, Oscar; Zalba, Guillermo; Burks, Deborah J.; Díez, Javier; Andrés, Vicente

    2008-01-01

    OBJECTIVE: The mechanisms underlying accelerated atherosclerosis in metabolic syndrome (MetS) patients remain poorly defined. In the mouse, complete disruption of insulin receptor substrate-2 (Irs2) causes insulin resistance, MetS-like manifestations, and accelerates atherosclerosis. Here, we performed human, mouse, and cell culture studies to gain insight into the contribution of defective Irs2 signaling to MetS-associated alterations. METHODS AND RESULTS: In circulating leukocytes from ...

  5. Staphylococcal Toxic Shock Syndrome 2000–2006: Epidemiology, Clinical Features, and Molecular Characteristics

    OpenAIRE

    DeVries, Aaron S.; Lindsey Lesher; Patrick M Schlievert; Tyson Rogers; Lourdes G Villaume; Richard Danila; Ruth Lynfield

    2011-01-01

    INTRODUCTION: Circulating strains of Staphylococcus aureus (SA) have changed in the last 30 years including the emergence of community-associated methicillin-resistant SA (MRSA). A report suggested staphylococcal toxic shock syndrome (TSS) was increasing over 2000-2003. The last population-based assessment of TSS was 1986. METHODS: Population-based active surveillance for TSS meeting the CDC definition using ICD-9 codes was conducted in the Minneapolis-St. Paul area (population 2,642,056) fro...

  6. 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

  7. Molecular analysis of FGFR 2 and associated clinical observations in two Chinese families with Crouzon syndrome.

    Science.gov (United States)

    Lin, Ying; Gao, Hongbin; Ai, Siming; Eswarakumar, Jacob V P; Li, Tao; Liu, Bingqian; Jiang, Hongye; Liu, Yuhua; Liu, Xialin; Li, Yonghao; Ni, Yao; Chen, Jiangna; Lin, Zhuoling; Liang, Xiaoling; Jin, Chenjin; Huang, Xinhua; Lu, Lin; Liu, Yizhi

    2016-09-01

    Crouzon syndrome, a dominantly inherited disorder and the most common type of craniosynostosis syndrome, is caused by mutations in the fibroblast growth factor receptor 2 (FGFR 2) gene, and characterized by craniosynostosis, shallow orbits, ocular proptosis, midface hypoplasia and a curved, beak‑like nose. The purpose of the present study was to investigate the fibroblast growth factor receptor 2 (FGFR 2) gene in two Chinese families with Crouzon syndrome and to characterize the associated clinical features. Two families underwent complete ophthalmic examination, and three patients in two families were diagnosed with Crouzon syndrome. Genomic DNA was extracted from leukocytes of peripheral blood samples, which were collected from the family members and 200 unrelated control subjects from the same population. Exons 8 and 10 of the FGFR 2 gene were amplified using polymerase chain reaction analysis and were directly sequenced. Ophthalmic examinations, including best‑corrected visual acuity, slit‑lamp examination, fundus examination and Computerized Tomography scans, and physical examinations were performed to exclude systemic diseases. These patients were affected with shallow orbits and ocular proptosis, accompanied by midface hypoplasia, craniosynostosis, strabismus or papilloedema, with clinically normal hands and feet. A heterozygous FGFR 2 missense mutation, c.811‑812insGAG (p.273insGlu) in exon 8 was identified in the affected individual, but not in the unaffected family members or the normal control individuals in family 1. In family 2, another heterozygous FGFR 2 missense mutation, c.842A>G (P.Tyr281Cys or Y281C), in exon 8 was identified in the affected boy and his mother, but not in the unaffected family members or the normal control individuals. Although FGFR 2 gene mutations and polymorphisms have been reported in various ethnic groups, particularly in the area of osteology, the present study reported for the first time, to the best of

  8. Detailed molecular and clinical investigation of a child with a partial deletion of chromosome 11 (Jacobsen syndrome

    Directory of Open Access Journals (Sweden)

    Peitsidis Panagiotis

    2009-12-01

    Full Text Available Abstract Background Jacobsen syndrome (JBS is a rare chromosomal disorder leading to multiple physical and mental impairment. This syndrome is caused by a partial deletion of chromosome 11, especially subband 11q24.1 has been proven to be involved. Clinical cases may easily escape diagnosis, however pancytopenia or thrombocytopenia may be indicative for JBS. Results We report a 7.5 years old boy presenting with speech development delay, hearing impairment and abnormal platelet function. High resolution SNP oligonucleotide microarray analysis revealed a terminal deletion of 11.4 Mb in size, in the area 11q24.1-11qter. This specific deletion encompasses around 170 genes. Other molecular techniques such as fluorescence in situ hybridization and multiplex ligation-dependent probe amplification were used to confirm the array-result. Discussion Our results suggest that the identification and detailed analysis of similar patients with abnormal platelet function and otherwise mild clinical features will contribute to identification of more patients with 11q deletion and JBS.

  9. C-reactive protein, high-molecular-weight adiponectin and development of metabolic syndrome in the Japanese general population: a longitudinal cohort study.

    Directory of Open Access Journals (Sweden)

    Yoshifumi Saisho

    Full Text Available AIMS: To clarify predictive values of C-reactive protein (CRP and high-molecular-weight (HMW adiponectin for development of metabolic syndrome. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study of Japanese workers who had participated in an annual health checkup in 2007 and 2011. A total of 750 subjects (558 men and 192 women, age 46±8 years who had not met the criteria of metabolic syndrome and whose CRP and HMW-adiponectin levels had been measured in 2007 were enrolled in this study. Associations between CRP, HMW-adiponectin and development of metabolic syndrome after 4 years were assessed by logistic regression analysis and their predictive values were compared by receiver operating characteristic analysis. RESULTS: Among 750 subjects, 61 (8.1% developed metabolic syndrome defined by modified National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III criteria and 53 (7.1% developed metabolic syndrome defined by Japan Society for the Study of Obesity (JASSO in 2011. Although CRP and HMW-adiponectin were both significantly correlated with development of metabolic syndrome, multivariate logistic regression analysis revealed that HMW-adiponectin but not CRP was associated with metabolic syndrome independently of BMI or waist circumference. Adding these biomarkers to BMI or waist circumference did not improve the predictive value for metabolic syndrome. CONCLUSION: Our findings indicate that the traditional markers of adiposity such as BMI or waist circumference remain superior markers for predicting metabolic syndrome compared to CRP, HMW-adiponectin, or the combination of both among the Japanese population.

  10. Changes in the folding landscape of the WW domain provide a molecular mechanism for an inherited genetic syndrome

    Science.gov (United States)

    Pucheta-Martinez, Encarna; D’Amelio, Nicola; Lelli, Moreno; Martinez-Torrecuadrada, Jorge L.; Sudol, Marius; Saladino, Giorgio; Gervasio, Francesco Luigi

    2016-07-01

    WW domains are small domains present in many human proteins with a wide array of functions and acting through the recognition of proline-rich sequences. The WW domain belonging to polyglutamine tract-binding protein 1 (PQBP1) is of particular interest due to its direct involvement in several X chromosome-linked intellectual disabilities, including Golabi-Ito-Hall (GIH) syndrome, where a single point mutation (Y65C) correlates with the development of the disease. The mutant cannot bind to its natural ligand WBP11, which regulates mRNA processing. In this work we use high-field high-resolution NMR and enhanced sampling molecular dynamics simulations to gain insight into the molecular causes the disease. We find that the wild type protein is partially unfolded exchanging among multiple beta-strand-like conformations in solution. The Y65C mutation further destabilizes the residual fold and primes the protein for the formation of a disulphide bridge, which could be at the origin of the loss of function.

  11. Maternally Inherited Diabetes and Deafness (MIDD Syndrome: A Clinical and Molecular Genetic Study of a Taiwanese Family.

    Directory of Open Access Journals (Sweden)

    Yung-Nien Chen

    2004-01-01

    Full Text Available We report on a case of a 48-year-old woman presenting with maternally inherited diabetesmellitus and deafness (MIDD syndrome. Molecular genetic analysis and clinical evaluationwere conducted in the patient and her 4 children to investigate the interrelationbetween an MIDD-associated mitochondrial DNA (mtDNA mutation and clinical manifestations.Various symptoms and markers of MIDD, including seizures, migraines, shortstature, mental retardation, and stroke-like episodes, were reviewed. Diabetes mellitus (DMwas studied by oral glucose tolerance and glucagon stimulation tests. Hearing impairmentwas determined by standard hearing tests and a brainstem auditory evoked potential test.The A3243G and T3271C transitional mutations of mtDNA were investigated from muscleand/or leukocytes and hair follicles. Mitochondrial-related symptoms were not found in thechildren, although they all harbored a heteroplasmic A3243G transition of mtDNA, asdetected in screened samples. For the patient, the proportion of mutant mtDNA was highestin muscle cells followed by hair follicles and then leukocytes. Moreover, the proportion ofmutant mtDNA was also higher in hair follicles than in leukocytes for asymptomatic familymembers. This Taiwanese MIDD family was found to have the A3243G point mutation asrevealed from molecular genetic studies of leukocytes, hair follicles, and muscle tissue.However, no correlation was found between the proportion of mutant mtDNA and clinicalfeatures of any family member.

  12. Narcolepsy and familial advanced sleep-phase syndrome: molecular genetics of sleep disorders.

    NARCIS (Netherlands)

    Tafti, M.; Dauvilliers, Y.; Overeem, S.

    2007-01-01

    Sleep disorders are very prevalent and represent an emerging worldwide epidemic. However, research into the molecular genetics of sleep disorders remains surprisingly one of the least active fields. Nevertheless, rapid progress is being made in several prototypical disorders, leading recently to the

  13. Alport alloantibodies but not Goodpasture autoantibodies induce murine glomerulonephritis: protection by quinary crosslinks locking cryptic α3(IV) collagen autoepitopes in vivo.

    Science.gov (United States)

    Luo, Wentian; Wang, Xu-Ping; Kashtan, Clifford E; Borza, Dorin-Bogdan

    2010-09-15

    The noncollagenous (NC1) domains of alpha3alpha4alpha5(IV) collagen in the glomerular basement membrane (GBM) are targets of Goodpasture autoantibodies or Alport posttransplant nephritis alloantibodies mediating rapidly progressive glomerulonephritis. Because the autoepitopes but not the alloepitopes become cryptic upon assembly of alpha3alpha4alpha5NC1 hexamers, we investigated how the accessibility of B cell epitopes in vivo influences the development of glomerulonephritis in mice passively immunized with human anti-GBM Abs. Alport alloantibodies, which bound to native murine alpha3alpha4alpha5NC1 hexamers in vitro, deposited linearly along the mouse GBM in vivo, eliciting crescentic glomerulonephritis in Fcgr2b(-/-) mice susceptible to Ab-mediated inflammation. Goodpasture autoantibodies, which bound to murine alpha3NC1 monomer and dimer subunits but not to native alpha3alpha4alpha5NC1 hexamers in vitro, neither bound to the mouse GBM in vivo nor induced experimental glomerulonephritis. This was due to quinary NC1 crosslinks, recently identified as sulfilimine bonds, which comprehensively locked the cryptic Goodpasture autoepitopes in the mouse GBM. In contrast, non-crosslinked alpha3NC1 subunits were identified as a native target of Goodpasture autoantibodies in the GBM of squirrel monkeys, a species susceptible to Goodpasture autoantibody-mediated nephritis. Thus, crypticity of B cell autoepitopes in tissues uncouples potentially pathogenic autoantibodies from autoimmune disease. Crosslinking of alpha3alpha4alpha5NC1 hexamers represents a novel mechanism averting autoantibody binding and subsequent tissue injury by posttranslational modifications of an autoantigen. PMID:20709951

  14. Alport alloantibodies but not Goodpasture autoantibodies induce murine glomerulonephritis: Protection by quinary crosslinks locking cryptic α3(IV) collagen autoepitopes in vivo 1

    Science.gov (United States)

    Luo, Wentian; Wang, Xu-Ping; Kashtan, Clifford E.; Borza, Dorin-Bogdan

    2010-01-01

    The noncollagenous (NC1) domains of α3α4α5(IV) collagen in the glomerular basement membrane (GBM) are targets of Goodpasture autoantibodies or Alport post-transplant nephritis alloantibodies mediating rapidly progressive glomerulonephritis. Because the autoepitopes but not the alloepitopes become cryptic upon assembly of α3α4α5NC1 hexamers, we investigated how the accessibility of B cell epitopes in vivo influences the development of glomerulonephritis in mice passively immunized with human anti-GBM antibodies. Alport alloantibodies, which bound to native murine α3α4α5NC1 hexamers in vitro, deposited linearly along the mouse GBM in vivo, eliciting crescentic glomerulonephritis in Fcgr2b−/− mice susceptible to antibody-mediated inflammation. Goodpasture autoantibodies, which bound to murine α3NC1 monomer and dimer subunits but not to native α3α4α5NC1 hexamers in vitro, neither bound to the mouse GBM in vivo nor induced experimental glomerulonephritis. This was due to quinary NC1 cross-links, recently identified as sulfilimine bonds, which comprehensively locked the cryptic Goodpasture autoepitopes in the mouse GBM. In contrast, non-crosslinked α3NC1 subunits were identified as a native target of Goodpasture autoantibodies in the GBM of squirrel monkeys—a species susceptible to Goodpasture autoantibody-mediated nephritis. Thus, crypticity of B cell autoepitopes in tissues uncouples potentially pathogenic autoantibodies from autoimmune disease. Crosslinking of α3α4α5NC1 hexamers represents a novel mechanism averting autoantibody binding and subsequent tissue injury by post-translational modifications of an autoantigen. PMID:20709951

  15. Mowat-Wilson syndrome: neurological and molecular study in seven patients

    Directory of Open Access Journals (Sweden)

    José Albino da Paz

    2015-01-01

    Full Text Available Objective To present a seven-cases serie of Mowat-Wilson syndrome (MWS. Method All patients with positive mutation for the ZEB2 were evaluated by a geneticist and a neurologist, with clinical and laboratorial characterization. Results A peculiar facies and mental retardation were present in all patients. The Denver II scale showed intense delay in all aspects, especially fine motor and adaptive. Acquired microcephaly was observed in five patients. Only one patient did not present epilepsy. Epilepsy was focal and predominating in sleep, with status epilepticus in three patients. The initial seizure was associated with fever in most patients (4/6. The EEG showed epileptic focal activity (5/7. The imaging studies revealed total agenesis (4/7 and partial agenesis of the corpus callosum (1/7. Conclusion Physicians who care for patients with mental retardation and epilepsy should be aware of SMW.

  16. Malignant Tregs express low molecular splice forms of FOXP3 in Sézary syndrome

    DEFF Research Database (Denmark)

    Krejsgaard, T; Gjerdrum, L M; Ralfkiaer, E;

    2008-01-01

    growth of non-malignant T cells. The Treg phenotype and the production of suppressive cytokines are driven by aberrant activation of Jak3 independent of the FOXP3 splice forms. In contrast to wt FOXP3, the low molecular splice forms of FOXP3 have no inhibitory effect on nuclear factor-kappaB (NF...... SS. We demonstrate that malignant T cells in 8 of 15 patients stain positive with an anti-FOXP3 antibody. Western blotting analysis shows expression of two low molecular splice forms of FOXP3, but not of wild-type (wt) FOXP3. The malignant T cells produce interleukin-10 and TGF-beta and suppress the......-kappaB) activity in reporter assays which is in keeping with a constitutive NF-kappaB activity in the malignant T cells. In conclusion, we show that the malignant T cells express low molecular splice forms of FOXP3 and function as Tregs. Furthermore, we provide evidence that FOXP3 splice forms are functionally...

  17. Molecular and Cellular Mechanisms of Myelodysplastic Syndrome: Implications on Targeted Therapy.

    Science.gov (United States)

    Gill, Harinder; Leung, Anskar Y H; Kwong, Yok-Lam

    2016-01-01

    Myelodysplastic syndrome (MDS) is a group of heterogeneous clonal hematopoietic stem cell disorders characterized by cytopenia, ineffective hematopoiesis, and progression to secondary acute myeloid leukemia in high-risk cases. Conventional prognostication relies on clinicopathological parameters supplemented by cytogenetic information. However, recent studies have shown that genetic aberrations also have critical impacts on treatment outcome. Moreover, these genetic alterations may themselves be a target for treatment. The mutation landscape in MDS is shaped by gene aberrations involved in DNA methylation (TET2, DNMT3A, IDH1/2), histone modification (ASXL1, EZH2), the RNA splicing machinery (SF3B1, SRSF2, ZRSR2, U2AF1/2), transcription (RUNX1, TP53, BCOR, PHF6, NCOR, CEBPA, GATA2), tyrosine kinase receptor signaling (JAK2, MPL, FLT3, GNAS, KIT), RAS pathways (KRAS, NRAS, CBL, NF1, PTPN11), DNA repair (ATM, BRCC3, DLRE1C, FANCL), and cohesion complexes (STAG2, CTCF, SMC1A, RAD21). A detailed understanding of the pathogenetic mechanisms leading to transformation is critical for designing single-agent or combinatorial approaches in target therapy of MDS. PMID:27023522

  18. Molecular findings of Colombian patients with type VI mucopolysaccharidosis (Maroteaux–Lamy syndrome)

    Science.gov (United States)

    Giraldo, Gustavo Adolfo; Ayala-Ramírez, Paola; Prieto, Juan Carlos; García-Robles, Reggie; Acosta, Johanna Carolina

    2015-01-01

    Introduction Maroteaux–Lamy syndrome, or mucopolysaccharidosis (MPS) type VI, is an autosomal recessive lysosomal storage disease caused by a deficient activity of the enzyme arylsulfatase B (ARSB), required to degrade dermatan sulfate. The onset and progression of the disease vary, producing a spectrum of clinical presentation. So far, 133 mutations have been reported. The aim of this study is to determine the mutations in the ARSB gene that are responsible for this disease in Colombian patients. Results Fourteen patients with clinical manifestations and biochemical diagnosis of MPS VI were studied, including two siblings. The 8 exons of the gene were directly sequenced from patients' DNA, and 14 mutations were found. 57% of these mutations had not been previously reported (p.H111P, p.C121R, p.G446S, p.*534W, p.S334I, p.H147P, c.900T > G, and c.1531_1553del) and 43% had been previously reported (p.G144R, p.W322*, p.G302R, p.C447F, p.L128del, and c.1143-1G > C). Of the previously reported mutations, 80% have been associated with severe phenotypes and 20% with intermediate-severe phenotypes. Bioinformatic predictions indicate that the new mutations reported in this paper are also highly deleterious. Conclusions Most of the Colombian patients in this study had private mutations. PMID:26909334

  19. Molecular genetic analysis in 14 Czech Kabuki syndrome patients is confirming the utility of phenotypic scoring.

    Science.gov (United States)

    Paděrová, J; Holubová, A; Simandlová, M; Puchmajerová, A; Vlčková, M; Malíková, M; Pourová, R; Vejvalková, S; Havlovicová, M; Šenkeříková, M; Ptáková, N; Drábová, J; Geryk, J; Maver, A; Křepelová, A; Macek, M

    2016-09-01

    Kabuki syndrome (KS) is a dominantly inherited disorder mainly due to de novo pathogenic variation in KMT2D or KDM6A genes. Initially, a representative cohort of 14 Czech cases with clinical features suggestive of KS was analyzed by experienced clinical geneticists in collaboration with other specialties, and observed disease features were evaluated according to the 'MLL2-Kabuki score' defined by Makrythanasis et al. Subsequently, the aforementioned genes were Sanger sequenced and copy number variation analysis was performed by MLPA, followed by genome-wide array CGH testing. Pathogenic variants in KMT2D resulting in protein truncation in 43% (6/14; of which 3 are novel) of all cases were detected, while analysis of KDM6A was negative. MLPA analysis was negative in all instances. One female patient bears a 6.6 Mb duplication of the Xp21.2-Xp21.3 region that is probably disease causing. Subjective KS phenotyping identified predictive clinical features associated with the presence of a pathogenic variant in KMT2D. We provide additional evidence that this scoring approach fosters prioritization of patients prior to KMT2D sequencing. We conclude that KMT2D sequencing followed by array CGH is a diagnostic strategy with the highest diagnostic yield. PMID:26841933

  20. Molecular genetic analysis of individuals with Williams syndrome and supravalvar aortic stenosis

    Energy Technology Data Exchange (ETDEWEB)

    Smoot, L.B.; Lacro, R.V.; Kunkel, L.M. [Children`s Hospital, Boston, MA (United States); Pober, B. [Yale Univ., New Haven, CT (United States)

    1994-09-01

    Mutations at the elastin locus (chromosome 7q11.23) have been demonstrated in individuals with Williams syndrome (WS) and familial supravalvar aortic stenosis (SVAS). Relationships between elastin mutations and vascular and/or neurodevelopmental pathology have yet to be defined. In determining phenotype-genotype correlations in WS/SVAS, we examined 35 individuals with sporadic WS, families with SVAS affecting multiple members, and sporadic cases of isolated obstructive vascular disease. Full length elastin cDNA was used to probe a human genomic library from which multiple elastin genomic clones have been isolated and ordered relative to the elastin gene, covering a minimum of 35 kb. (Additional genomic clones are being obtained by {open_quote}walking{close_quote} 5{prime} and 3{prime} to elastin.) Elastin genomic clones were used as probes in fluorescent in situ hybridization of metaphase chromosomes from WS/SVAS patients. Preliminary analysis confirms elastin deletions in WS patients, but have not yet been demonstrated in patients with isolated vascular disease using this technique. Results of deletional analysis in individuals representing a wide spectrum of phenotypes will be presented.

  1. Prenatal molecular testing for Beckwith-Wiedemann and Silver-Russell syndromes

    DEFF Research Database (Denmark)

    Eggermann, Thomas; Brioude, Frédéric; Russo, Silvia;

    2016-01-01

    the cases. In addition, 10% of the SRS patients carry a maternal uniparental disomy of chromosome 7 11p15.5. There is an increasing demand for prenatal testing of these disorders owing to family history, indicative prenatal ultrasound findings or aberrations involving chromosomes 7 and 11. The complex...... molecular findings underlying these disorders are a challenge not only for laboratories offering these tests but also for geneticists counseling affected families. The scope of counseling must consider the range of detectable disturbances and their origin, the lack of precise quantitative knowledge...

  2. Localisation of the gene responsible for fechtner syndrome in a region <600 Kb on 22q11-q13.

    Science.gov (United States)

    Cusano, R; Gangarossa, S; Forabosco, P; Caridi, G; Ghiggeri, G M; Russo, G; Iolascon, A; Ravazzolo, R; Seri, M

    2000-11-01

    Fechtner syndrome is an autosomal dominant disorder which has been thought to be a variant of Alport syndrome. It is characterised by nephritis, sensorineural hearing loss and eye abnormalities, as well as by macrothrombocytopenia and polymorphonuclear inclusion bodies. Recently, the Fechtner syndrome has been mapped in a 5.5 Mb region on the long arm of chromosome 22 by linkage analysis in an extended Israeli family. We describe here the genetic refinement of the Fechtner critical interval to a region less than 600 Kb by linkage analysis performed in a large Italian pedigree. The presence of several recombination events allowed the disease gene to be localised between markers D22S278 and D22S426, in a region containing only two non-recombinant markers, D22S1173 and D22S283. This interval, spanning <600 Kb on genomic DNA, has been entirely sequenced and contains six known and three putative genes. PMID:11093280

  3. Virtual Screening and Molecular Docking Study of Bloom’s Syndrome Protein (BLM for Finding Potential Lead Drug Candidate

    Directory of Open Access Journals (Sweden)

    Manoj Kumar Verma

    2014-06-01

    Full Text Available Increased levels of locus-specific mutations within the BLM result in development of Bloom Syndrome and patients are found to be immune deficient. HRDC domain amino acid Lys1270 is presumably to play role in mediating interactions with DNA. Single point mutation of Lys1270 (K1270V reduces the potency of Double Holliday junction (DHJ DNA unwinding so BLM lead to its functional loss. Quadruplex formation have role in immunoglobulin heavy chain switching and inhibiting RecQ helicases activity in-vitro in BLM. Variety of G-Quadruplex ligands are employed by molecular docking for arriving at lead compound identification. The scoring function of docking results describes protein-ligand interaction and it conjointly instructed that docking of ligand at mutational binding site shows some repressing function to make potential lead drug molecule. So as to know the elaborated purposeful functional mechanism of protein and to relate impact of mutation with function and activity; dock screening, hit identification and lead optimization facilitate in design of lead drug compound.

  4. Proxy molecular diagnosis from whole-exome sequencing reveals Papillon-Lefevre syndrome caused by a missense mutation in CTSC.

    Directory of Open Access Journals (Sweden)

    A Mesut Erzurumluoglu

    Full Text Available Papillon-Lefevre syndrome (PLS is an autosomal recessive disorder characterised by severe early onset periodontitis and palmoplantar hyperkeratosis. A previously reported missense mutation in the CTSC gene (NM_001814.4:c.899G>A:p.(G300D was identified in a homozygous state in two siblings diagnosed with PLS in a consanguineous family of Arabic ancestry. The variant was initially identified in a heterozygous state in a PLS unaffected sibling whose whole exome had been sequenced as part of a previous Primary ciliary dyskinesia study. Using this information, a proxy molecular diagnosis was made on the PLS affected siblings after consent was given to study this second disorder found to be segregating within the family. The prevalence of the mutation was then assayed in the local population using a representative sample of 256 unrelated individuals. The variant was absent in all subjects indicating that the variant is rare in Saudi Arabia. This family study illustrates how whole-exome sequencing can generate findings and inferences beyond its primary goal.

  5. ISOLATION OF EGG DROP SYNDROME VIRUS AND ITS MOLECULAR CHARACTERIZATION USING SODIUM DODECYL SULPHATE POLYACRYLAMIDE GEL ELECTROPHORESIS

    Directory of Open Access Journals (Sweden)

    M. H. Rasool, S. U. Rahman and M. K. Mansoor

    2005-10-01

    Full Text Available Six isolates of egg drop syndrome (EDS virus were recovered from five different outbreaks of EDS in commercial laying hens in and around Faisalabad. The aberrant eggs were fed to the susceptible laying hens for experimental induction of infection. The samples from infected birds (egg washing, cloacal swabs, oviducts and spleens were collected, processed and inoculated into 11-day old duck embryos. The presence of virus in harvested allanto-amniotic fluid was monitored by spot and microhaemagglutination tests and confirmed by haemagglutination inhibition and agar gel precipitation tests. The EDS virus grew well in duck embryos and agglutinated only avian but not mammalian red blood cells. These isolates were purified through velocity density gradient centrifugation. Protein concentration was determined through Lowry method and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE was conducted by loading 300 µg protein concentration on 12.5% gel using discontinuous buffer system. All the six isolates showed 13 polypeptides, which were identical to those described in the referral EDS-76 virus (strain-127. The molecular weights of the polypeptides ranged from 6.5 KDa to 126 KDa.

  6. Molecular Origin of Gerstmann-Str ussler-Scheinker Syndrome: Insight from Computer Simulation of an Amyloidogenic Prion Peptide

    Energy Technology Data Exchange (ETDEWEB)

    Diadone, Isabella [University of L' Aquila, L' Aquila, Italy; DiNola, Alfredo [University of Rome; Smith, Jeremy C [ORNL

    2011-01-01

    Prion proteins become pathogenic through misfolding. Here, we characterize the folding of a peptide consisting of residues 109 122 of the Syrian hamster prion protein (the H1 peptide) and of a more amyloidogenic A117V point mutant that leads in humans to an inheritable form of the Gerstmann-Straeussler-Scheinker syndrome. Atomistic molecular dynamics simulations are performed for 2.5 s. Both peptides lose their -helical starting conformations and assume a -hairpin that is structurally similar in both systems. In each simulation several unfolding/refolding events occur, leading to convergence of the thermodynamics of the conformational states to within 1 kJ/mol. The similar stability of the -hairpin relative to the unfolded state is observed in the two peptides. However, substantial differences are found between the two unfolded states. A local minimum is found within the free energy unfolded basin of the A117V mutant populated by misfolded collapsed conformations of comparable stability to the -hairpin state, consistent with increased amyloidogenicity. This population, in which V117 stabilizes a hydrophobic core, is absent in the wild-type peptide. These results are supported by simulations of oligomers showing a slightly higher stability of the associated structures and a lower barrier to association for the mutated peptide. Hence, a single point mutation carrying only two additional methyl groups is here shown to be responsible for rather dramatic differences of structuring within the unfolded (misfolded) state.

  7. Staphylococcal toxic shock syndrome 2000-2006: epidemiology, clinical features, and molecular characteristics.

    Directory of Open Access Journals (Sweden)

    Aaron S DeVries

    Full Text Available INTRODUCTION: Circulating strains of Staphylococcus aureus (SA have changed in the last 30 years including the emergence of community-associated methicillin-resistant SA (MRSA. A report suggested staphylococcal toxic shock syndrome (TSS was increasing over 2000-2003. The last population-based assessment of TSS was 1986. METHODS: Population-based active surveillance for TSS meeting the CDC definition using ICD-9 codes was conducted in the Minneapolis-St. Paul area (population 2,642,056 from 2000-2006. Medical records of potential cases were reviewed for case criteria, antimicrobial susceptibility, risk factors, and outcome. Superantigen PCR testing and PFGE were performed on available isolates from probable and confirmed cases. RESULTS: Of 7,491 hospitalizations that received one of the ICD-9 study codes, 61 TSS cases (33 menstrual, 28 non-menstrual were identified. The average annual incidence per 100,000 of all, menstrual, and non-menstrual TSS was 0.52 (95% CI, 0.32-0.77, 0.69 (0.39-1.16, and 0.32 (0.12-0.67, respectively. Women 13-24 years had the highest incidence at 1.41 (0.63-2.61. No increase in incidence was observed from 2000-2006. MRSA was isolated in 1 menstrual and 3 non-menstrual cases (7% of TSS cases; 1 isolate was USA400. The superantigen gene tst-1 was identified in 20 (80% of isolates and was more common in menstrual compared to non-menstrual isolates (89% vs. 50%, p = 0.07. Superantigen genes sea, seb and sec were found more frequently among non-menstrual compared to menstrual isolates [100% vs 25% (p = 0.4, 60% vs 0% (p<0.01, and 25% vs 13% (p = 0.5, respectively]. DISCUSSION: TSS incidence remained stable across our surveillance period of 2000-2006 and compared to past population-based estimates in the 1980s. MRSA accounted for a small percentage of TSS cases. tst-1 continues to be the superantigen associated with the majority of menstrual cases. The CDC case definition identifies the most severe cases and has

  8. Molecular Genetic Testing in Reward Deficiency Syndrome (RDS: Facts and Fiction

    Directory of Open Access Journals (Sweden)

    Kenneth Blum

    2015-03-01

    Full Text Available Background: The Brain Reward Cascade (BRC is an interaction of neurotransmitters and their respective genes to control the amount of dopamine released within the brain. Any variations within this pathway, whether genetic or environmental (epigenetic, may result in addictive behaviors or RDS, which was coined to define addictive behaviors and their genetic components. Methods: To carry out this review we searched a number of important databases including: Filtered: Cochrane Systematic reviews; DARE; Pubmed Central Clinical Quaries; National Guideline Clearinghouse and unfiltered resources: PsychINFO; ACP PIER; PsychSage; Pubmed/Medline. The major search terms included: dopamine agonist therapy for Addiction; dopamine agonist therapy for Reward dependence; dopamine antagonistic therapy for addiction; dopamine antagonistic therapy for reward dependence and neurogenetics of RDS. Results: While there are many studies claiming a genetic association with RDS behavior, not all are scientifically accurate. Conclusion: Albeit our bias, this Clinical Pearl discusses the facts and fictions behind molecular genetic testing in RDS and the significance behind the development of the Genetic Addiction Risk Score (GARSPREDX™, the first test to accurately predict one’s genetic risk for RDS.

  9. Molecular analysis of chromosome 21 in a patient with a phenotype of down syndrome and apparently normal karyotype

    Energy Technology Data Exchange (ETDEWEB)

    Ahlbom, B.E.; Wadelius, C.; Zech, L.; Anneren, G. [Uppsala Univ. (Sweden)] [and others

    1996-06-28

    Down syndrome (DS) is caused in most cases by the presence of an extra chromosome 21. It has been shown that the DS phenotype is produced by duplication of only a small part of the long arm of chromosome 21, the 21q22 region, including and distal to locus D21S55. We present molecular investigations on a woman with clinically typical DS but apparently normal chromosomes. Her parents were consanguineous and she had a sister with a DS phenotype, who died at the age of 15 days. Repeated cytogenetic investigations (G-banding and high resolution banding) on the patient and her parents showed apparently normal chromosomes. Autoradiographs of quantitative Southern blots of DNAs from the patient, her parents, trisomy 21 patients, and normal controls were analyzed after hybridization with unique DNA sequences regionally mapped on chromosome 21. Sequences D21S59, D21S1, D21S11, D21S8, D21S17, D21S55, ERG, D21S15, D21S112, and COL6A1 were all found in two copies. Fluorescent in situ hybridization with a chromosome 21-specific genomic library showed no abnormalities and only two copies of chromosome 21 were detected. Nineteen markers from the critical region studied with polymerase chain reaction amplification of di- and tetranucleotide repeats did not indicate any partial trisomy 21. From his study we conclude that the patient does not have any partial submicroscopic trisomy for any segment of chromosome 21. It seems reasonable to assume that she suffers from an autosomal recessive disorder which is phenotypically indistinguishable from DS. 23 refs., 6 figs., 3 tabs.

  10. Molecular definition of the chromosome 7 deletion in Williams syndrome and parent-of-origin effects on growth

    Energy Technology Data Exchange (ETDEWEB)

    Perez Jurado, L.A.; Peoples, R.; Francke, U. [Stanford Univ. School of Medicine, CA (United States)] [and others

    1996-10-01

    Williams syndrome (WS) is a developmental disorder with variable phenotypic expression associated, in most cases, with a hemizygous deletion of part of chromosomal band 7q11.23 that includes the elastin gene (ELN). We have investigated the frequency and size of the deletions, determined the parental origin, and correlated the molecular results with the clinical findings in 65 WS patients. Hemizygosity at the ELN locus was established by typing of two intragenic polymorphisms, quantitative Southern analysis, and/or FISH. Polymorphic markers covering the deletion and flanking regions were ordered by a combination of genetic and physical mapping. Genotyping of WS patients and available parents for 13 polymorphisms revealed that of 65 clinically defined WS patients, 61 (94%) had a deletion of the ELN locus and were also hemizygous (or non-informative) at loci D7S489B, D7S2476, D7S613, D7S2472, and D7S1870. None of the four patients without ELN deletion was hemizygous at any of the polymorphic loci studied. All patients were heterozygous (or noninformative) for centromeric (D7S1816, D7S1483, and D7S653) and telomeric (D7S489A, D7S675, and D7S669) flanking loci. The genetic distance between the most-centromeric deleted locus, D7S489B, and the most-telomeric one, D7S1870, is 2 cM. The breakpoints cluster at {approximately}1 cM to either side of ELN. In 39 families informative for parental origin, all deletions were de novo, and 18 were paternally and 21 maternally derived. Comparison of clinical data, collected in a standardized quantifiable format, revealed significantly more severe growth retardation and microcephaly in the maternal deletion group. An imprinted locus, silent on the paternal chromosome and contributing to statural growth, may be affected by the deletion. 53 refs., 5 figs., 2 tabs.

  11. Audiometry

    Science.gov (United States)

    ... The following conditions may affect test results: Acoustic neuroma Acoustic trauma Age-related hearing loss Alport syndrome ... Mosby Elsevier; 2010:chap 190. Read More Acoustic neuroma Acoustic trauma Age-related hearing loss Alport syndrome ...

  12. Detailed molecular and clinical investigation of a child with a partial deletion of chromosome 11 (Jacobsen syndrome)

    OpenAIRE

    Peitsidis Panagiotis; Thomaidis Loretta; Papoulidis Ioannis; Louizou Eirini; Kefalas Konstantinos; Neroutsou Rosita; Orru Sandro; Manolakos Emmanouil; Sotiriou Sotirios; Kitsos George; Tsoplou Panagiota; Petersen Michael B; Metaxotou Aikaterini

    2009-01-01

    Abstract Background Jacobsen syndrome (JBS) is a rare chromosomal disorder leading to multiple physical and mental impairment. This syndrome is caused by a partial deletion of chromosome 11, especially subband 11q24.1 has been proven to be involved. Clinical cases may easily escape diagnosis, however pancytopenia or thrombocytopenia may be indicative for JBS. Results We report a 7.5 years old boy presenting with speech development delay, hearing impairment and abnormal platelet function. High...

  13. A molecular clock dates the common ancestor of European-type porcine reproductive and respiratory syndrome virus at more than 10 years before the emergence of disease

    DEFF Research Database (Denmark)

    Forsberg, Roald; Oleksiewicz, Martin B.; Krabbe Petersen, Anne Mette;

    2001-01-01

    The disease caused by porcine reproductive and respiratory syndrome virus (PRRSV) emerged independently and almost simultaneously in Europe (1990) and North America (1987). The original reservoir of the virus and the date it entered the pig populations is not known. In this study, we demonstrate...... an accurate molecular clock for the European PRRSV ORF 3 gene, place the root in the genealogy, estimate the rate of nucleotide substitution, and date the most recent common viral ancestor of the data set to 1979; more than 10 years before the onset of the European epidemic. Based on these findings, we...

  14. Molecularly proven mosaicism in phenotypically normal parent of a girl with Freeman-Sheldon Syndrome caused by a pathogenic MYH3 mutation.

    Science.gov (United States)

    Hague, Jennifer; Delon, Isabelle; Brugger, Kim; Martin, Howard; Abbs, Stephen; Park, Soo-Mi

    2016-06-01

    We report a case of a female child who has classical Freeman-Sheldon syndrome (FSS) associated with a previously reported recurrent pathogenic heterozygous missense mutation, c.2015G > A, p. (Arg672His), in MYH3 where the phenotypically normal mother is a molecularly confirmed mosaic. To the best of our knowledge, this is the first report in the medical literature of molecularly confirmed parental mosaicism for a MYH3 mutation causing FSS. Since proven somatic mosaicism after having an affected child is consistent with gonadal mosaicism, a significantly increased recurrence risk is advised. Parental testing is thus essential for accurate risk assessment for future pregnancies and the use of new technologies with next generation sequencing (NGS) may improve the detection rate of mosaicism. © 2016 Wiley Periodicals, Inc. PMID:26996280

  15. The genetic basis of inherited anomalies of the teeth. Part 1: clinical and molecular aspects of non-syndromic dental disorders.

    Science.gov (United States)

    Bailleul-Forestier, Isabelle; Molla, Muriel; Verloes, Alain; Berdal, Ariane

    2008-01-01

    The genetic control of dental development represents a complex series of events, which can very schematically be divided in two pathways: specification of type, size and position of each dental organ, and specific processes for the formation of enamel and dentin. Several genes linked with early tooth positioning and development, belong to signalling pathways and have morphogenesis regulatory functions in morphogenesis of other organs where they are associated with the signalling pathways. Their mutations often show pleïotropic effects beyond dental morphogenesis resulting in syndromic developmental disorders. Some genes affecting early tooth development (MSX1, AXIN2) are associated with tooth agenesis and systemic features (cleft palate, colorectal cancer). By contrast, genes involved in enamel (AMELX, ENAM, MMP20, and KLK4) and dentin (DSPP) structures are highly specific for tooth. Mutations in these genes have been identified as causes of amelogenesis imperfecta, dentinogenesis imperfecta, dentin dysplasias and anomalies of teeth number (hypo-, oligo and anodontia), which only partially overlap with the classical phenotypic classifications of dental disorders. This review of genetic basis of inherited anomalies describes, in this first paper, the molecular bases and clinical features of inherited non-syndromic teeth disorders. And in a second part, the review focus on genetic syndromes with dental involvement. PMID:18499550

  16. Molecular typing of toxic shock syndrome toxin-1- and Enterotoxin A-producing methicillin-sensitive Staphylococcus aureus isolates from an outbreak in a neonatal intensive care unit.

    Science.gov (United States)

    Layer, Franziska; Sanchini, Andrea; Strommenger, Birgit; Cuny, Christiane; Breier, Ann-Christin; Proquitté, Hans; Bührer, Christoph; Schenkel, Karl; Bätzing-Feigenbaum, Jörg; Greutelaers, Benedikt; Nübel, Ulrich; Gastmeier, Petra; Eckmanns, Tim; Werner, Guido

    2015-10-01

    Outbreaks of Staphylococcus aureus are common in neonatal intensive care units (NICUs). Usually they are documented for methicillin-resistant strains, while reports involving methicillin-susceptible S. aureus (MSSA) strains are rare. In this study we report the epidemiological and molecular investigation of an MSSA outbreak in a NICU among preterm neonates. Infection control measures and interventions were commissioned by the Local Public Health Authority and supported by the Robert Koch Institute. To support epidemiological investigations molecular typing was done by spa-typing and Multilocus sequence typing; the relatedness of collected isolates was further elucidated by DNA SmaI-macrorestriction, microarray analysis and bacterial whole genome sequencing. A total of 213 neonates, 123 healthcare workers and 205 neonate parents were analyzed in the period November 2011 to November 2012. The outbreak strain was characterized as a MSSA spa-type t021, able to produce toxic shock syndrome toxin-1 and Enterotoxin A. We identified seventeen neonates (of which two died from toxic shock syndrome), four healthcare workers and three parents putatively involved in the outbreak. Whole-genome sequencing permitted to exclude unrelated cases from the outbreak and to discuss the role of healthcare workers as a reservoir of S. aureus on the NICU. Genome comparisons also indicated the presence of the respective clone on the ward months before the first colonized/infected neonates were detected. PMID:26321006

  17. Pfeiffer syndrome

    Directory of Open Access Journals (Sweden)

    Fryns Jean-Pierre

    2006-06-01

    Full Text Available Abstract Pfeiffer syndrome is a rare autosomal dominantly inherited disorder that associates craniosynostosis, broad and deviated thumbs and big toes, and partial syndactyly on hands and feet. Hydrocephaly may be found occasionally, along with severe ocular proptosis, ankylosed elbows, abnormal viscera, and slow development. Based on the severity of the phenotype, Pfeiffer syndrome is divided into three clinical subtypes. Type 1 "classic" Pfeiffer syndrome involves individuals with mild manifestations including brachycephaly, midface hypoplasia and finger and toe abnormalities; it is associated with normal intelligence and generally good outcome. Type 2 consists of cloverleaf skull, extreme proptosis, finger and toe abnormalities, elbow ankylosis or synostosis, developmental delay and neurological complications. Type 3 is similar to type 2 but without a cloverleaf skull. Clinical overlap between the three types may occur. Pfeiffer syndrome affects about 1 in 100,000 individuals. The disorder can be caused by mutations in the fibroblast growth factor receptor genes FGFR-1 or FGFR-2. Pfeiffer syndrome can be diagnosed prenatally by sonography showing craniosynostosis, hypertelorism with proptosis, and broad thumb, or molecularly if it concerns a recurrence and the causative mutation was found. Molecular genetic testing is important to confirm the diagnosis. Management includes multiple-staged surgery of craniosynostosis. Midfacial surgery is performed to reduce the exophthalmos and the midfacial hypoplasia.

  18. Molecular epidemiology and functional assessment of novel allelic variants of SLC26A4 in non-syndromic hearing loss patients with enlarged vestibular aqueduct in China.

    Directory of Open Access Journals (Sweden)

    Yongyi Yuan

    Full Text Available BACKGROUND: Mutations in SLC26A4, which encodes pendrin, are a common cause of deafness. SLC26A4 mutations are responsible for Pendred syndrome and non-syndromic enlarged vestibular aqueduct (EVA. The mutation spectrum of SLC26A4 varies widely among ethnic groups. To investigate the incidence of EVA in Chinese population and to provide appropriate genetic testing and counseling to patients with SLC26A4 variants, we conducted a large-scale molecular epidemiological survey of SLC26A4. METHODS: A total of 2352 unrelated non-syndromic hearing loss patients from 27 different regions of China were included. Hot spot regions of SLC26A4, exons 8, 10 and 19 were sequenced. For patients with one allelic variant in the hot spot regions, the other exons were sequenced one by one until two mutant alleles had been identified. Patients with SLC26A4 variants were then examined by temporal bone computed tomography scan for radiological diagnosis of EVA. Ten SLC26A4 variants were cloned for functional study. Confocal microscopy and radioisotope techniques were used to examine the membrane expression of pendrin and transporter function. RESULTS: Of the 86 types of variants found, 47 have never been reported. The ratio of EVA in the Chinese deaf population was at least 11%, and that in patients of Han ethnicity reached at least 13%. The mutational spectrum and mutation detection rate of SLC26A4 are distinct among both ethnicities and regions of Mainland China. Most of the variants caused retention of pendrin in the intracellular region. All the mutant pendrins showed significantly reduced transport capability. CONCLUSION: An overall description of the molecular epidemiological findings of SLC26A4 in China is provided. The functional assessment procedure can be applied to identification of pathogenicity of variants. These findings are valuable for genetic diagnosis, genetic counseling, prenatal testing and pre-implantation diagnosis in EVA families.

  19. Importance of molecular cell biology investigations in human medicine in the story of the Hutchinson-Gilford progeria syndrome

    Czech Academy of Sciences Publication Activity Database

    Raška, Ivan

    2010-01-01

    Roč. 3, č. 3 (2010), s. 89-93. ISSN 1337-6853 Grant ostatní: GA MŠk(CZ) LC535 Institutional research plan: CEZ:AV0Z50110509 Keywords : laminopathies * Hutchinson-Gilford progeria syndrome * progerin Subject RIV: EA - Cell Biology

  20. Korean Society for Laboratory Medicine Practice Guidelines for the Molecular Diagnosis of Middle East Respiratory Syndrome During an Outbreak in Korea in 2015.

    Science.gov (United States)

    Ki, Chang Seok; Lee, Hyukmin; Sung, Heungsup; Kim, Sinyoung; Seong, Moon Woo; Yong, Dongeun; Kim, Jae Seok; Lee, Mi Kyung; Kim, Mi Na; Choi, Jong Rak; Kim, Jeong Ho

    2016-05-01

    For two months between May and July 2015, a nationwide outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) occurred in Korea. On June 3, 2015, the Korean Society for Laboratory Medicine (KSLM) launched a MERS-CoV Laboratory Response Task Force (LR-TF) to facilitate clinical laboratories to set up the diagnosis of MERS-CoV infection. Based on the WHO interim recommendations, the Centers for Disease Control and Prevention of United States guidelines for MERS-CoV laboratory testing, and other available resources, the KSLM MERS-CoV LR-TF provided the first version of the laboratory practice guidelines for the molecular diagnosis of MERS-CoV to the clinical laboratories on June 12, 2015. The guidelines described here are an updated version that includes case definition, indications for testing, specimen type and protocols for specimen collection, specimen packing and transport, specimen handling and nucleic acid extraction, molecular detection of MERS-CoV, interpretation of results and reporting, and laboratory safety. The KSLM guidelines mainly focus on the molecular diagnosis of MERS-CoV, reflecting the unique situation in Korea and the state of knowledge at the time of publication. PMID:26915607

  1. Rearrangements of the Williams–Beuren syndrome locus: molecular basis and implications for speech and language development

    OpenAIRE

    Osborne, Lucy R.; Mervis, Carolyn B.

    2007-01-01

    The Williams–Beuren syndrome (WBS) locus on human chromosome 7q11.23 is flanked by complex chromosome-specific low-copy repeats that mediate recurrent genomic rearrangements of the region. Common genomic rearrangements arise through unequal meiotic recombination and result in complex but distinct behavioural and cognitive phenotypes. Deletion of 7q11.23 results in WBS, which is characterised by mild to moderate intellectual disability or learning difficulties, with relative cognitive strength...

  2. A medaka model to study the the molecular basis of Microphthalmia with Linear Skin defects (MLS) syndrome

    OpenAIRE

    Indrieri, Alessia

    2010-01-01

    The Microphthalmia with linear skin defects (MLS) syndrome is an X- linked dominant male-lethal neuro-developmental disorder associated to mutations in the holocytochrome c-type synthetase (HCCS) transcript. Female patients display unilateral or bilateral microphthalmia and linear skin defects, additional features include central nervous system (CNS) malformation and mental retardation. HCCS codifies a mitochondrial protein that catalyzes the attachment of heme to both apocytochrome c and c1,...

  3. Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome

    OpenAIRE

    Minegishi, Yoshiyuki; Saito, Masako; Nagasawa, Masayuki; Takada, Hidetoshi; Hara, Toshiro; Tsuchiya, Shigeru; Agematsu, Kazunaga; Yamada, Masafumi; Kawamura, Nobuaki; Ariga, Tadashi; Tsuge, Ikuya; Karasuyama, Hajime

    2009-01-01

    Hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by atopic manifestations and susceptibility to infections with extracellular pathogens, typically Staphylococcus aureus, which preferentially affect the skin and lung. Previous studies reported the defective differentiation of T helper 17 (Th17) cells in HIES patients caused by hypomorphic STAT3 mutations. However, the apparent contradiction between the systemic Th17 deficiency and the skin/lung-restricted susceptibility to...

  4. Molecular signature of clinical severity in recovering patients with severe acute respiratory syndrome coronavirus (SARS-CoV)

    OpenAIRE

    Wu Ting-Shu; Chiang Ping-Cherng; Eng Hock-Liew; Liu Jien-Wei; Wang Yi-Hsi; Lin Meng-Chih; Yang Kuender D; Chen Lung-Kun; Wei Min-Li; Chen En-Shih; Chao Angel; Chen Chun-Houh; Lee Yun-Shien; Tsao Kuo-Chein; Huang Chung-Guei

    2005-01-01

    Abstract Background Severe acute respiratory syndrome (SARS), a recent epidemic human disease, is caused by a novel coronavirus (SARS-CoV). First reported in Asia, SARS quickly spread worldwide through international travelling. As of July 2003, the World Health Organization reported a total of 8,437 people afflicted with SARS with a 9.6% mortality rate. Although immunopathological damages may account for the severity of respiratory distress, little is known about how the genome-wide gene expr...

  5. Novel molecular variants of the Na-K-2Cl cotransporter gene are responsible for antenatal Bartter syndrome.

    OpenAIRE

    Vargas-Poussou, R; Feldmann, D. (Dirk); Vollmer, M.; Konrad, M; Kelly, L.; van den Heuvel, L.P.; Tebourbi, L; Brandis, M.; Karolyi, L.; Hebert, S C; Lemmink, H.H.; Deschênes, G.; Hildebrandt, F.; Seyberth, H. W.; Guay-Woodford, L.M.

    1998-01-01

    Antenatal Bartter syndrome is a variant of inherited renal-tubular disorders associated with hypokalemic alkalosis. This disorder typically presents as a life-threatening condition beginning in utero, with marked fetal polyuria that leads to polyhydramnios and premature delivery. Another hallmark of this variant is a marked hypercalciuria and, as a secondary consequence, the development of nephrocalcinosis and osteopenia. We have analyzed 15 probands belonging to 13 families and have performe...

  6. Molecular and cytogenetic characterization of a recurrent unbalanced translocation (4;21) (p16.3;q22.1): Relevance to the Wolf-Hirschhorn and Down syndrome critical regions

    Energy Technology Data Exchange (ETDEWEB)

    Sebastio, G.; Perone, L.; Guzzetta, V. [Universita Federico II, Naples (Italy)] [and others

    1996-05-17

    We report on an aneuploidy syndrome due to the unbalanced segregation of a familial translocation (4;21)(p16.3;q22.1) causing a partial 4p monosomy and a partial 21q trisomy. The three affected children presented with severe failure to thrive, short stature, microcephaly, profound hypotonia, and mental retardation. The face, very similar in the three children, is characterized by frontal bossing, upslanting of the palpebral fissures, short nose, and deep set ears, giving the overall appearance of the Down syndrome. The molecular study has defined the aneuploid segment on both 4p and 21q. Most of the Down syndrome critical region was found to be trisomic, while only part of the candidate Wolf-Hirschhorn syndrome critical region was deleted, suggesting that this region is not critical for the major malformations characteristic for WHS. 15 refs., 5 figs., 1 tab.

  7. Molecular characterization of two proximal deletion breakpoint regions in both Prader-Willi and Angelman syndrome patients

    Energy Technology Data Exchange (ETDEWEB)

    Christian, S.L.; Huang, B.; Ledbetter, D.H. [National Institutes of Health, Bethesda, MD (United States)] [and others

    1995-07-01

    Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct mental retardation syndromes caused by paternal and maternal deficiencies, respectively, in chromosome 15q11{minus}q13. Approximately 70% of these patients have a large deletion of {approximately}4 Mb extending from D15S9 (ML34) through D15S12 (IR10A). To further characterize the deletion breakpoints proximal to D15S9, three new polymorphic microsatellite markers were developed that showed observed heterozygosities of 60%-87%. D15S541 and D15S542 were isolated for YAC A124A3 containing the D15S18 (IR39) locus. D15S543 was isolated from a cosmid cloned from the proximal right end of YAC 254B5 containing the D15S9 (ML34) locus. Gene-centromere mapping of these markers, using a panel of ovarian teratomas of known meiotic origin, extended the genetic map of chromosome 15 by 2-3 cM toward the centromere. Analysis of the more proximal S541/S542 markers on 53 Prader-Willi and 33 Angelman deletion patients indicated two classes of patients: 44% (35/80) of the informative patients were deleted for these markers (class I), while 56% (45/80) were not deleted (class II), with no difference between PWS and AS. In contrast, D15S543 was deleted in all informative patients (13/48) or showed the presence of a single allele (in 35/48 patients), suggesting that this marker is deleted in the majority of PWS and AS cases. These results confirm the presence of two common proximal deletion breakpoint regions in both Prader-Willi and Angelman syndromes and are consistent with the same deletion mechanism being responsible for paternal and maternal deletions. One breakpoint region lies between D15S541/S542 and D15S543, with an additional breakpoint region being proximal to D15S541/S542. 46 refs., 2 figs., 3 tabs.

  8. Molecular docking analyses of Avicennia marinaderived phytochemicals against white spot syndrome virus (WSSV) envelope protein-VP28

    OpenAIRE

    Sahu, Sunil Kumar; KATHIRESAN, Kandasamy; Singh, Reena; Senthilraja, Poomalai

    2012-01-01

    White spot syndrome (WSS) is one of the most common and most disastrous diseases of shrimp worldwide. It causes up to 100% mortality within 3 to 4 days in commercial shrimp farms, resulting in large economic losses to the shrimp farming industry. VP28 envelope protein of WSSV is reported to play a key role in the systemic infection in shrimps. Considering the most sombre issue of viral disease in cultivated shrimp, the present study was undertaken to substantiate the inhibition potential of A...

  9. Beals Syndrome

    Science.gov (United States)

    ... Boards & Staff Annual Report & Financials Contact Us Donate Marfan & Related Disorders What is Marfan Syndrome? What are ... the syndrome. How does Beals syndrome compare with Marfan syndrome? People with Beals syndrome have many of ...

  10. Diagnosis of Familial Wolf-Hirschhorn Syndrome due to a Paternal Cryptic Chromosomal Rearrangement by Conventional and Molecular Cytogenetic Techniques

    Science.gov (United States)

    Venegas-Vega, Carlos A.; Zepeda, Luis M.; Garduño-Zarazúa, Luz M.; Berumen, Jaime; Kofman, Susana; Cervantes, Alicia

    2013-01-01

    The use of conventional cytogenetic techniques in combination with fluorescent in situ hybridization (FISH) and single-nucleotide polymorphism (SNP) microarrays is necessary for the identification of cryptic rearrangements in the diagnosis of chromosomal syndromes. We report two siblings, a boy of 9 years and 9 months of age and his 7-years- and 5-month-old sister, with the classic Wolf-Hirschhorn syndrome (WHS) phenotype. Using high-resolution GTG- and NOR-banding karyotypes, as well as FISH analysis, we characterized a pure 4p deletion in both sibs and a balanced rearrangement in their father, consisting in an insertion of 4p material within a nucleolar organizing region of chromosome 15. Copy number variant (CNV) analysis using SNP arrays showed that both siblings have a similar size of 4p deletion (~6.5 Mb). Our results strongly support the need for conventional cytogenetic and FISH analysis, as well as high-density microarray mapping for the optimal characterization of the genetic imbalance in patients with WHS; parents must always be studied for recognizing cryptic balanced chromosomal rearrangements for an adequate genetic counseling. PMID:23484094

  11. Vaccination and Infection as Causative Factors in Japanese Patients With Rasmussen Syndrome: Molecular Mimicry and HLA Class I

    Directory of Open Access Journals (Sweden)

    Yukitoshi Takahashi

    2006-01-01

    Full Text Available Rasmussen syndrome is an intractable epilepsy with a putative causal relation with cellular and humoral autoimmunity. Almost half of the patients have some preceding causative factors, with infections found in 38.2%, vaccinations in 5.9% and head trauma in 8.9% of Japanese patients. In a patient with seizure onset after influenza A infections, cross-reaction of the patient's lymphocytes with GluRε2 and influenza vaccine components was demonstrated by lymphocyte stimulation test. Database analyses revealed that influenza A virus hemagglutinin and GluRε2 molecules contain peptides with the patient's HLA class I binding motif (HLA ࢤ A*0201. The relative risks of HLA class I genotypes for Rasmussen syndrome are 6.1 (A*2402, 6.4 (A*0201, 6.3 (A*2601 and 11.4 (B*4601. The relative risks of HLA class I-A and B haplotypes are infinity (A*2601+B*5401, 21.1 (A*2402+B*1501, 13.3 (A*2402+B*4801 and 5.1 (A*2402+B*5201. Some alleles and haplotypes of HLA class I may be the risk factors in Japanese patients. Cross-reactivity of cytotoxic T lymphocytes may contribute to the processes leading from infection to the involvement of CNS.

  12. Molecular cloning of t(2;7)(p24.3;p14.2), a novel chromosomal translocation in myelodysplastic syndrome-derived acute myeloid leukemia.

    Science.gov (United States)

    Fujita, Kazuhiro; Sanada, Masashi; Harada, Hiroshi; Mori, Hiraku; Niikura, Haruo; Omine, Mitsuhiro; Inazawa, Johji; Imoto, Issei

    2009-06-01

    In this study, we report the molecular structure of the breakpoint region in a new chromosomal translocation, t(2;7)(p24.3;p14.2), in a case of acute myeloid leukemia transformed from myelodysplastic syndrome (MDS). An extensive fluorescence in situ hybridization (FISH) analysis showed that NAG (2p24.3) and ELMO1 (7p14.2) were involved at the breakpoints of t(2;7)(p24.3;p14.2). Furthermore, we detected a novel chimeric transcript consisting of NAG and ELMO1. Interestingly, this transcript encoded a truncated molecular form of 3'ELMO1 as the result of a frameshift caused by the chromosomal translocation. Although this study does not provide direct evidence that a defect in NAG-ELMO1 plays a role in the pathogenesis or the leukemic change in MDS, it does suggest that defects in NAG-ELMO1 potentially contributed to the leukemic progression in this case. PMID:19407829

  13. Molecular Characterization of a Heterothallic Mating System in Pseudogymnoascus destructans, the Fungus Causing White-Nose Syndrome of Bats

    Czech Academy of Sciences Publication Activity Database

    Palmer, J.M.; Kubátová, Alena; Nováková, Alena; Minnis, A.M.; Kolařík, Miroslav; Lindner, D.L.

    2014-01-01

    Roč. 4, č. 9 (2014), s. 1755-1763. ISSN 2160-1836 R&D Projects: GA ČR(CZ) GAP506/12/1064 Institutional support: RVO:61388971 Keywords : geomyces * sexual reproduction * mating type Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.198, year: 2014

  14. Clinical features and molecular genetic analysis of a boy with Prader-Willi syndrome caused by an imprinting defect

    DEFF Research Database (Denmark)

    Schulze, A; Hansen, Claus; Baekgaard, P; Blichfeldt, S; Petersen, M B; Tommerup, Niels; Brøndum-Nielsen, K

    1997-01-01

    recurrence has been reported. In rare cases, PWS is associated with lack of gene expression from the paternal allele due to an imprinting defect. We report the clinical features and the molecular genetic analysis of the first Danish child with PWS due to a defect of the putative imprinting centre (IC). When...

  15. Molecular characterization of porcine circovirus 2 isolated from diseased pigs co-infected with porcine reproductive and respiratory syndrome virus

    Directory of Open Access Journals (Sweden)

    Liu Chengqian

    2010-10-01

    Full Text Available Abstract In this study, we isolated a porcine circovirus 2 (PCV2 strain from piglets co-infected with porcine reproductive and respiratory syndrome virus (PRRSV. The complete genome of this strain was sequenced, phylogenetic and polymorphic analyses were carried out. BLAST searches revealed the highest sequence identity (99.5% nt and 99.3% aa to Guangxi strain EF675230. The phylogenetic tree showed that clustering of the isolates didn't strongly correlate to geographical distribution. Polymorphic analyses demonstrated that the amino acids at most of the polymorphic sites in Open Reading Frame 1(ORF1 and 2 (ORF2belong to the same amino acid group according to chemical or structural properties, and revealed that highly polymorphic regions overlapped with the known immunoreactive epitopes of ORF2.

  16. Comprehensive clinical studies in 34 patients with molecularly defined UPD(14)pat and related conditions (Kagami-Ogata syndrome).

    Science.gov (United States)

    Kagami, Masayo; Kurosawa, Kenji; Miyazaki, Osamu; Ishino, Fumitoshi; Matsuoka, Kentaro; Ogata, Tsutomu

    2015-11-01

    Paternal uniparental disomy 14 (UPD(14)pat) and epimutations and microdeletions affecting the maternally derived 14q32.2 imprinted region lead to a unique constellation of clinical features such as facial abnormalities, small bell-shaped thorax with a coat-hanger appearance of the ribs, abdominal wall defects, placentomegaly, and polyhydramnios. In this study, we performed comprehensive clinical studies in patients with UPD(14)pat (n=23), epimutations (n=5), and microdeletions (n=6), and revealed several notable findings. First, a unique facial appearance with full cheeks and a protruding philtrum and distinctive chest roentgenograms with increased coat-hanger angles to the ribs constituted the pathognomonic features from infancy through childhood. Second, birth size was well preserved, with a median birth length of ±0 SD (range, -1.7 to +3.0 SD) and a median birth weight of +2.3 SD (range, +0.1 to +8.8 SD). Third, developmental delay and/or intellectual disability was invariably present, with a median developmental/intellectual quotient of 55 (range, 29-70). Fourth, hepatoblastoma was identified in three infantile patients (8.8%), and histological examination in two patients showed a poorly differentiated embryonal hepatoblastoma with focal macrotrabecular lesions and well-differentiated hepatoblastoma, respectively. These findings suggest the necessity of an adequate support for developmental delay and periodical screening for hepatoblastoma in the affected patients, and some phenotypic overlap between UPD(14)pat and related conditions and Beckwith-Wiedemann syndrome. On the basis of our previous and present studies that have made a significant contribution to the clarification of underlying (epi)genetic factors and the definition of clinical findings, we propose the name 'Kagami-Ogata syndrome' for UPD(14)pat and related conditions. PMID:25689926

  17. Explanation on the Molecular Mechanism of "Lack of Vital Essence Resulting in Deficiency Syndrome" of Asthenia Cold Syndrome and Asthenia Hot Syndrome Rats%基因芯片技术阐释虚寒证与虚热证大鼠“精气夺则虚”的分子机制

    Institute of Scientific and Technical Information of China (English)

    韩冰冰; 王世军

    2013-01-01

    目的:采用基因芯片技术阐释虚寒证与虚热证大鼠“精气夺则虚”的共同分子机制.方法:使用中药复方建立虚寒证、虚热证大鼠模型,基因芯片检测大鼠肝脏基因表达,筛选差异表达基因并进行聚类分析,荧光定量PCR验证芯片结果.结果:聚类结果显示虚寒模型组与虚热模型组基因表达轮廓具有相似性,与空白对照组有差异.虚寒模型组、虚热模型组与空白对照组相比较,存在共有差异表达基因28条,其中16条免疫应答相关基因.结论:虚寒证与虚热证大鼠均出现了免疫应答相关基因表达的显著改变,这可能是虚寒证与虚热证大鼠“精气夺则虚”的分子机制.%Objective:To explain the molecular mechanism of "lack of vital essence resulting in deficiency syndrome" in both asthenia cold syndrome rats and asthenia hot syndrome rats by gene chip technology.Methods:The Asthenia cold and hot syndrome rats models were induced by compound preparation of Traditional Chinese Medicine.The liver gene expression in each group was detected by gene chip.We selected the differential expression genes,analyzed the genes by cluster and conducted the significant analysis on the genetic function of differential genes.A part of genes were selected to test the accuracy of results by RT -PCR.Results:The cluster analysis showed the profile of genes expression of asthenia cold model group was similar to asthenia hot model group.Both asthenia cold model group and asthenia hot model group were different from control group.Among asthenia cold model group,asthenia hot model group and control group,there were 28 strips of differential expression gene,among which 16 stips were about immune response.Conclusion:Obvious changes have been both arose in asthenia cold model group and asthenia hot model group about genes immune response,which is possibly the molecular mechanism of "lack of vital essence resulting in deficiency syndrome".

  18. Clinical and molecular characterization of Rubinstein-Taybi syndrome patients carrying distinct novel mutations of the EP300 gene.

    Science.gov (United States)

    Negri, G; Milani, D; Colapietro, P; Forzano, F; Della Monica, M; Rusconi, D; Consonni, L; Caffi, L G; Finelli, P; Scarano, G; Magnani, C; Selicorni, A; Spena, S; Larizza, L; Gervasini, C

    2015-02-01

    Rubinstein-Taybi syndrome (RSTS) is a rare congenital neurodevelopmental disorder characterized by postnatal growth deficiency, skeletal abnormalities, dysmorphic features and cognitive deficit. Mutations in two genes, CREBBP and EP300, encoding two homologous transcriptional co-activators, have been identified in ˜55% and ˜3-5% of affected individuals, respectively. To date, only eight EP300-mutated RSTS patients have been described and 12 additional mutations are reported in the database LOVD. In this study, EP300 analysis was performed on 33 CREBBP-negative RSTS patients leading to the identification of six unreported germline EP300 alterations comprising one deletion and five point mutations. All six patients showed a convincing, albeit mild, RSTS phenotype with minor skeletal anomalies, slight cognitive impairment and few major malformations. Beyond the expansion of the RSTS-EP300-mutated cohort, this study indicates that EP300-related RSTS cases occur more frequently than previously thought (˜8% vs 3-5%); furthermore, the characterization of novel EP300 mutations in RSTS patients will enhance the clinical practice and genotype-phenotype correlations. PMID:24476420

  19. Molecular-genetic risk assessement of determining angiotensin-converting enzyme hyperactivity in hemorrhagic fever with renal syndrome

    Directory of Open Access Journals (Sweden)

    Ildar R. Minniakhmetov

    2012-09-01

    Full Text Available The present study was designed to investigate changes in angiotensin-converting enzyme (ACE blood activity and angiotensin II type 1 receptor gene polymorphism as a possible disease predictor in hemorrhagic fever with renal syndrome (HFRS. Four hundred and nine patients (346 males and 63 females with HFRS serologic confirmation were enrolled in the study. Their age ranged from 15 to 65 years. ACE blood activity was assessed kinetically using the Bühlmann (Switzerland kit. Peripheral blood genomic DNA was isolated by a phenol-chloroform extraction. The genotyping of DNA loci was done using a polymerase chain reaction of DNA synthesis. Statistically, ACE blood activity was significantly higher throughout the entire HFRS course with diverse severity apart from the feverish phase of moderate-to-severe uncomplicated disease forms. *A1166 and *C1166 alleles, *A1166/*A1166 and *C1166/*C1166 genotypes of angiotensin II type 1 receptor gene were not associated with HFRS severity. The results of this study indicate that high ACE activity has not adaptive characteristics due to abnormalities in angiotensin II reception. It is an adequate metabolic response of the body to endotheliotropic virus activity.

  20. Recurrent Johanson-Blizzard syndrome in a triplet pregnancy complicated by urethral obstruction sequence: a clinical, molecular, and immunohistochemical approach.

    Science.gov (United States)

    Schoner, Katharina; Fritz, Barbara; Huelskamp, Georg; Louwen, Frank; Zenker, Martin; Moll, Roland; Rehder, Helga

    2012-01-01

    We report on a triplet pregnancy of consanguineous parents with one fetus being affected by recurrent Johanson-Blizzard syndrome (JBS). At autopsy in the 35th gestational week, the affected triplet presented with an especially severe and lethal manifestation of the disorder as compared to his elder affected brother and to cases in the literature, thus exemplifying great interfamilial and intrafamilial phenotypic variability. Arhinencephaly and cystic renal dysplasia associated with urethral obstruction sequence were features not described previously in the literature. In addition to the lack of exocrine acini as the characteristic feature of JBS, the pancreas revealed a resorptive inflammatory reaction with infiltration by eosinophilic granulocytes that focally dispersed onto islets of Langerhans, thus favoring a progressive destructive rather than primary dysplastic process and possibly explaining the occurrence of diabetes mellitus in later life. JBS maps to chromosome 15q15-q21.1 and is associated with mutations in the UBR1 gene. Testing the fetus and the affected sibling revealed a homozygous truncating mutation in UBR1. The resulting absence of the UBR1 protein was confirmed by Western blot. Immunohistochemical staining using a commercial anti-UBR1 antibody demonstrated staining, presumably artifactual. This finding suggests that, until an appropriately validated antibody has been identified, this modality should not be utilized for diagnosis or confirmation of this disorder. PMID:21711208

  1. Molecular Epidemiological Investigation of Infectious Hypodermal and Hematopoietic Necrosis Virus and Taura Syndrome Virus in Penaeus Vannamei Cultured in China

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The Infectious hypodermal and hematopoietic necrosis virus (IHHNV) and Taura syndrome virus (TSV) are two important shrimp viruses in cultured shrimp in America. These two viruses were transmitted to China at the beginning of the 21st century. In this study, 214 shrimp samples of Penaeus vannamei were collected from seven different areas of China and tested by PCR for IHHNV and TSV infection. The results showed that there were a high prevalence of IHHNV (65.42%) and low prevalence of TSV (3.27%) in the tested samples. Several samples were found to be co-infected with these two viruses. A 3 kb fragment of 7 positive IHHNV samples and a structure protein region (ORF2) of three TSV positive samples were amplified and sequenced. The sequence comparison indicated that both IHHNV and TSV sequenced in China have a low genetic variations compared with the prototype IHHNV and TSV from Hawaii. Phylogenetic analysis showed that TSV isolates were clustered into two groups, Asia and America group, which was genetically correlated to geographic distribution.

  2. MOLECULAR DOCKING ANALYSES OF CYNODON DACTYLON DERIVED PHYTOCHEMICALS AGAINST WHITE SPOT SYNDROME VIRUS (WSSV STRUCTURAL PROTEIN VP26

    Directory of Open Access Journals (Sweden)

    Damayanthi Devi.I

    2015-05-01

    Full Text Available White spot disease is a major infectious disease of penaeid shrimps caused by the white spot syndrome virus (WSSV. The viral structural proteins are responsib le for binding virus to the cellular membranes of the host that is being systematically infected. An In silic o attempt was made to identify the potential drug to inhibit the WSSV spread of diseases. For that an effort , was made to deduce the antiviral potentiality of Cynodon dactylon derived phytochemicals with docking tec hnique. To stimulate the structure based drug design the, 3D structure of the VP26 (PDB-ID: 2EDM, a tegument protein thought to be i nvolved in the entry of WSSV nucleocapsid into the host nucleus, is retrieved from PDB datab ase and docking studies are carried out with the sketched phytochemical structures using GOLD software. Among the phytochemicals scr eened, luteolin and apigenin shows the best binding affinity with binding energies of 42.51 and 38.92 K.cal/m ol exhibiting the potential to block VP26 (2EDM protein of WSSV. This study will be helpful in developing novel antiviral drugs from plant sources against aquatic important pathogens.

  3. Analysis of molecular variation in porcine reproductive and respiratory syndrome virus in China between 2007 and 2012

    Institute of Scientific and Technical Information of China (English)

    Yuhang Cao; Hongsheng Ouyang; Mingjun Zhang; Fuwang Chen; Xin Yang; Daxing Pang; Linzhu Ren

    2014-01-01

    In the present study, 89 porcine reproductive and respiratory syndrome virus (PRRSV) isolates in China during 2007 to 2012 were randomly selected from the GenBank genetic sequence database. Evolutionary characteristics of these isolates were analyzed based on the sequences of non-struc-tural protein 2 (Nsp2) and glycoprotein 5 (GP5). The genetic variations of the isolates were also compared with six representative strains. The results showed that a high degree of genetic diversity exists among the PRRSV population in China. Highly pathogenic PRRSV isolates, with a discon-tinuous deletion of a 30 amino acid residue in the Nsp2 region, remained the most dominant virus throughout 2007-2012 in China. Owing to the extensive use of representative vaccine strains, natu-ral recombination events occurred between strains. Three isolates-HH08, DY, and YN-2011-were more closely related to vaccine strains than the other isolates. Both YN-2011 and DY were the evolu-tionary products of recombination events between strains SP and CH-1R. The results of the present study provide useful information for the epidemiology of PRRSV as well as for vaccine development.

  4. Detection of Bovine Leukemia Virus in Brains of Cattle with a Neurological Syndrome: Pathological and Molecular Studies

    Science.gov (United States)

    D'Angelino, Rubens Henrique Ramos; Pituco, Edviges Maristela; Villalobos, Eliana Monteforte Cassaro; Harakava, Ricardo; Gregori, Fábio

    2013-01-01

    Bovine leukemia virus (BLV) was investigated in the central nervous system (CNS) of cattle with neurological syndrome. A total of 269 CNS samples were submitted to nested-PCR (BLV env gene gp51), and the viral genotypes were identified. The nested-PCR was positive in 4.8% (13/269) CNS samples, with 2.7% (2/74) presenting at histological examination lesions of nonpurulent meningoencephalitis (NPME), whereas 5.6% (11/195) not presenting NPME (P > 0.05). No samples presented lymphosarcoma. The PCR products (437 bp) were sequenced and submitted to phylogenetic analysis by neighbor-joining and maximum composite likelihood methods, and genotypes 1, 5, and 6 were detected, corroborating other South American studies. The genotype 6 barely described in Brazil and Argentina was more frequently detected in this study. The identity matrices showed maximum similarity (100%) among some samples of this study and one from Argentina (FJ808582), recovered from GenBank. There was no association among the genotypes and NPME lesions. PMID:23710448

  5. Targeted therapy for hereditary cancer syndromes: hereditary breast and ovarian cancer syndrome, Lynch syndrome, familial adenomatous polyposis, and Li-Fraumeni syndrome.

    Science.gov (United States)

    Agarwal, Rishi; Liebe, Sarah; Turski, Michelle L; Vidwans, Smruti J; Janku, Filip; Garrido-Laguna, Ignacio; Munoz, Javier; Schwab, Richard; Rodon, Jordi; Kurzrock, Razelle; Subbiah, Vivek

    2014-12-01

    Cancer genetics has rapidly evolved in the last two decades. Understanding and exploring the several genetic pathways in the cancer cell is the foundation of targeted therapy. Several genomic aberrations have been identified and their role in carcinogenesis is being explored. In contrast to most cancers where these mutations are acquired, patients with hereditary cancer syndromes have inherited genomic aberrations. The understanding of the molecular pathobiology in hereditary cancer syndromes has advanced dramatically. In addition, many molecularly targeted therapies have been developed that could have potential roles in the treatment of patients with hereditary cancer syndromes. In this review, we outline the presentation, molecular biology, and possible targeted therapies for two of the most widely recognized hereditary cancer syndromes -- hereditary breast and ovarian cancer syndrome and hereditary non-polyposis colorectal cancer syndrome (Lynch syndrome). We will also discuss other syndromes such as familial adenomatous polyposis and Li-Fraumeni syndrome (TP53). PMID:25549704

  6. GENETIC ASPECTS OF CONGENITAL LONG QT SYNDROME

    Directory of Open Access Journals (Sweden)

    A. A. Chernova

    2015-12-01

    Full Text Available The main symptoms and clinical types of long QT syndrome are described. Molecular genetic diagnostics and updated approaches to the management of patients with long QT syndrome arepresented.

  7. Antiphospholipid Syndrome

    Science.gov (United States)

    ... Awards Enhancing Diversity Find People About NINDS NINDS Antiphospholipid Syndrome Information Page Synonym(s): Hughes Syndrome Table of Contents ( ... research is being done? Clinical Trials What is Antiphospholipid Syndrome? Antiphospholipid syndrome (APS) is an autoimmune disorder caused ...

  8. Molecular Detection and Identification of Α-L-Iduronidase Gene Mutations in 5 Iranian Families Suspected for Muller Syndrome (Mucopolysaccharidosis I

    Directory of Open Access Journals (Sweden)

    B Nasr- Esfahani

    2007-07-01

    Full Text Available Introduction: Mucopolysaccharidosis I (MPS-I is an autosomal recessive lysosomal storage diseases, caused by α-L-iduronidase (IDUA enzyme deficiency. The clinical manifestations of MPS-I patients are variable ranging from severe to mild, and therefore prediction of disease severity is difficult. From when IDUA gene has been cloned more than 109 distinct mutations have been identified in it and this number is increasing. This mutation analysis has provided some molecular explanations for the range of MPS-I phenotypes. The aim of this study was identification and molecular characterization of IDUA gene mutations in our subset of MPS I patients. Methods: The present study performed on 5 Iranian families, each with a suspected child for MPS-I. Initially by using enzyme activity assay, the Hurler syndrome was verified and then presence of L123R mutation was evaluated by PCR-SSCP. Finally by PCR amplification of all 14 exons of the gene, SSCP and sequencing the mutations underlying the disease were identified and characterized. Results: The detected mutations turned to be L123R (in 2 patients, W402X, P533R and G51D mutations in other 3 patients. Discussion: L123R mutation, which was reported for the first time from our centre, was also present in 2 of the patients of this study but other 3 mutations were not novel. From our results, as well others, it can be concluded that the range of mutations in IDUA gene differ in different geographical areas. This should be considered when designing mutation detection strategies for MPS-I.

  9. Molecular and clinical characterization of Waardenburg syndrome type I in an Iranian cohort with two novel PAX3 mutations.

    Science.gov (United States)

    Jalilian, Nazanin; Tabatabaiefar, Mohammad Amin; Farhadi, Mohammad; Bahrami, Tayeb; Emamdjomeh, Hesam; Noori-Daloii, Mohammad Reza

    2015-12-15

    Waardenburg syndrome (WS) is a disease of abnormal neural-crest derived melanocyte development characterized by hearing loss and pigmentary disturbances in hair, eyes and skin. WS is subdivided into four major types, WS1-WS4, where WS1 is recognized by the presence of dystopia canthorum, with PAX3 being the only known gene involved. This study aimed at investigating PAX3 mutations and clinical characteristics of WS1 in a group of Iranian patients. A total of 12 WS1 patients from four unrelated Iranian families were enrolled. Waardenburg consortium guidelines were used for WS1 diagnosis. A detailed family history was traced and a thorough clinical examination was performed for all participants. Furthermore, WS1 patients underwent screening for PAX3 mutations using PCR-sequencing. Dystopia canthorum, broad high nasal root and synophrys were observed in all patients. Early graying, hair discoloration, hypoplastic blue eyes (characteristic brilliant blue iris) and hearing loss were the most common features observed, while heterochromia iridis was the least frequently observed sign among the studied Iranian WS1 patients. Genetic analysis of PAX3 revealed four mutations including c.667C>T, c.784C>T, c.951delT and c.451+3A>C. Two of the four mutations reported here (c.951delT and c.451+3A>C) are being reported for the first time in this study. Our data provide insight into genotypic and phenotypic spectrum of WS1 in an Iranian series of patients. Our results expand the spectrum of PAX3 mutations and may have implications for the genetic counseling of WS in Iran. PMID:26275939

  10. Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: a molecular approach

    Science.gov (United States)

    Soldi, Sara; Vasileiadis, Sotirios; Uggeri, Francesca; Campanale, Mariachiara; Morelli, Lorenzo; Fogli, Maria Vittoria; Calanni, Fiorella; Grimaldi, Maria; Gasbarrini, Antonio

    2015-01-01

    Rifaximin, with its low systemic absorption, may represent a treatment of choice for irritable bowel syndrome (IBS), mainly due to its ability to act on IBS pathogenesis, through the influence on gut microbiota. The aim of the present study was to assess, by biomolecular tools, the rifaximin active modulation exerted on gut microbiota of non-constipated IBS patients. Fifteen non-constipated IBS subjects were treated with 550 mg rifaximin three times a day for 14 days. Stool samples were collected before starting the treatment, at the end of it, and after a 6-week washout period. Real-time polymerase chain reaction, denaturing gradient gel electrophoresis, and next-generation sequencing were applied to all the samples to verify and quantify possible microbial fluctuations. Rifaximin treatment did not affect the overall composition of the microbiota of the treated subjects, inducing fluctuations in few bacterial groups, balanced by the replacement of homologs or complementary bacterial groups. Rifaximin appeared to influence mainly potentially detrimental bacteria, such as Clostridium, but increasing the presence of some species, such as Faecalibacterium prausnitzii. A decrease in the Firmicutes/Bacteroidetes ratio after 14 days of treatment and bacterial profiles with higher biodiversity were observed during the follow-up compared to baseline. Rifaximin treatment, although effective on IBS symptom relief and normalization of lactulose breath test, did not induce dramatic shifts in the microbiota composition of the subjects, stimulating microbial reorganization in some populations toward a more diverse composition. It was not possible to speculate on differences of fecal microbiota modification between responders vs nonresponders and to correlate the quali-/quantitative modification of upper gastrointestinal microbiota and clinical response. PMID:26673000

  11. Molecular Pathology of 6 Novel GJB2 Allelic Variants Detected in Familial and Sporadic Iranian Non Syndromic Hearing Loss Cases

    Directory of Open Access Journals (Sweden)

    M Hashemzadeh Chaleshtori

    2008-09-01

    Full Text Available "nBackground: Mutations of GJB2 gene encoding connexion 26 are the most common cause of hearing loss in many popula­tions. A very wide spectrum of GJB2 gene mutations associated with hearing loss have been detected but pathogenic role has been tested only for a part of them. In this study, we have provided genetic evidence on the pathogenicity of our previ­ously reported novel GJB2 allelic variants. "nMethods: The pathogenic role of GJB2 allelic variants were assessed using co segregation of each allelic variant with hear­ing loss in family members, absence of the allelic variants in control populations, coexistence with a second GJB2 mutation, na­ture of the amino acid substitution and evolutionary conservation of the appropriate amino acid. "nResults: The GJB2 allelic variants including 363delC, 327delGGinsA, H16R and G200R have been co segregated with auto­somal recessive non syndromic hearing loss in five families and are not found in control subjects. The G130V and K102Q were found in heterozygous state in two deaf individuals. G130V results in an exchange a residue highly conserved among all the connexins but was found with a rate of 1% in control subjects and K102Q results in an exchange a residue not con­served among all the connexins and not identified in control subjects. "nConclusion: We conclude that, 363delC, 327delGGinsA, H16R and G200R may be pathogenic. However, the pathogenic­ity and inheritance of K102Q and G130V can not be assessed clearly and remains to be identified.

  12. Molecular Analysis of Collagen XVIII Reveals Novel Mutations, Presence of a Third Isoform, and Possible Genetic Heterogeneity in Knobloch Syndrome

    Science.gov (United States)

    Suzuki, O. T.; Sertié, A. L.; Der Kaloustian, V. M.; Kok, F.; Carpenter, M.; Murray, J.; Czeizel, A. E.; Kliemann, S. E.; Rosemberg, S.; Monteiro, M.; Olsen, B. R.; Passos-Bueno, M. R.

    2002-01-01

    Knobloch syndrome (KS) is a rare disease characterized by severe ocular alterations, including vitreoretinal degeneration associated with retinal detachment and occipital scalp defect. The responsible gene, COL18A1, has been mapped to 21q22.3, and, on the basis of the analysis of one family, we have demonstrated that a mutation affecting only one of the three COL18A1 isoforms causes this phenotype. We report here the results of the screening of both the entire coding region and the exon-intron boundaries of the COL18A1 gene (which includes 43 exons), in eight unrelated patients with KS. Besides 20 polymorphic changes, we identified 6 different pathogenic changes in both alleles of five unrelated patients with KS (three compound heterozygotes and two homozygotes). All are truncating mutations leading to deficiency of one or all collagen XVIII isoforms and endostatin. We have verified that, in exon 41, the deletion c3514-3515delCT, found in three unrelated alleles, is embedded in different haplotypes, suggesting that this mutation has occurred more than once. In addition, our results provide evidence of nonallelic genetic heterogeneity in KS. We also show that the longest human isoform (NC11-728) is expressed in several tissues (including the human eye) and that lack of either the short variant or all of the collagen XVIII isoforms causes similar phenotypes but that those patients who lack all forms present more-severe ocular alterations. Despite the small sample size, we found low endostatin plasma levels in those patients with mutations leading to deficiency of all isoforms; in addition, it seems that absence of all collagen XVIII isoforms causes predisposition to epilepsy. PMID:12415512

  13. Molecular dissection of a contiguous gene syndrome: Frequent submicroscopic deletions, evolutionarily conserved sequences, and a hypomethylated island in the Miller-Dieker chromosome region

    International Nuclear Information System (INIS)

    The Miller-Dieker syndrome (MDS), composed of characteristic facial abnormalities and a severe neuronal migration disorder affecting the cerebral cortex, is caused by visible or submicroscopic deletions of chromosome band 17p13. Twelve anonymous DNA markers were tested against a panel of somatic cell hybrids containing 17p deletions from seven MDS patients. All patients, including three with normal karyotypes, are deleted for a variable set of 5-12 markers. Two highly polymorphic VNTR (variable number of tandem repeats) probes, YNZ22 and YNH37, are codeleted in all patients tested and make molecular diagnosis for this disorder feasible. By pulsed-field gel electrophoresis, YNZ22 and YNH37 were shown to be within 30 kilobases (kb) of each other. Cosmid clones containing both VNTR sequences were identified, and restriction mapping showed them to be 100 kb were completely deleted in all patients, providing a minimum estimate of the size of the MDS critical region. A hypomethylated island and evolutionarily conserved sequences were identified within this 100-kb region, indications of the presence of one or more expressed sequences potentially involved in the pathophysiology of this disorder. The conserved sequences were mapped to mouse chromosome 11 by using mouse-rat somatic cell hybrids, extending the remarkable homology between human chromosome 17 and mouse chromosome 11 by 30 centimorgans, into the 17p telomere region

  14. From clinical suspect to molecular confirmation of noonan syndrome; contribution of “best practice” genetic counseling and new technical possibilities

    Directory of Open Access Journals (Sweden)

    Bukvic Nenad

    2015-01-01

    Full Text Available Noonan syndrome (NS is an autosomal dominant disorder, characterized by variable expressivity of clinical features such as: postnatal growth reduction, congenital heart disease, characteristic facial dysmorphisms and development delay. In ~75% of all NS cases, germline mutations involving RAS-MAPK signaling pathway genes (PTPN11, SOS1, RAF1, KRAS, NRAS, BRAF, SHOC2, MEK1, CBL are causative. We reported a case of 13-year-old girl [born at 36w by CS (BW 3250 g (~95°, BL 48 cm (~75°] referred for genetic counseling due to growth retardation, facial dysmorphisms, development delay and learning disability. After birth she presented frequent vomiting, with failure to thrive and at 5 months of age underwent surgery for intestinal malrotation. Because of short stature, Growth Hormone (GH therapy have been introduced at age of 3yrs up to 11yrs. Negative molecular testing for PTPN11 and SOS1 genes, normal female karyotype and aCGH analysis were observed. Objective examination: H 138 cm, (A; p.Val14Ile has been identified. Even though KRAS mutations are usually associated with NS severe phenotype with cardiac involvement (hypertrophic cardiomyopathy, this finding is not present in our patient.

  15. Molecular genetic analysis of a patient with Hunter syndrome (mucopolysaccharidosis type II) and {alpha}-L-iduronidase pseudodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Aronovich, E.L.; Whitley, C.B. [Univ. of Minnesota Medical School, Minneapolis, MN (United States)

    1994-09-01

    Mucopolysaccharidoses (MPS) type I and type II are lysosomal storage disorders resulting from {alpha}-L-iduronidase (IDUA) and iduronate-2-sulfatase (IDS) deficiency, respectively. The a priori probability that both disorders would occur in a single individual is less than 1-in-5-billion. Nevertheless, such a proband was referred for whom clinical findings (i.e., a male with coarse facies, dysostosis multiplex and mental retardation) and biochemical tests indicated these concomitant diagnoses. In repeated studies, leukocyte 4MU-{alpha}-L-iduronidase activities in this kindred were: <1.0 nmol/mg protein/hr in proband; 5.7 in sister; 4.9 in mother; 15.0 in father (normal range: 11.0-18.4). Multiple techniques, including automated sequencing of the entire IDS and IDUA coding regions, were employed to unravel the molecular genetic basis of these intriguing observations. The IDS mutation R468W - previously observed in 4 unrelated MPS II patients - was identified in the proband, his mother and sister, thus explaining their biochemical phenotypes. Additionally, the proband, his sister and father were found to be heterozygous for a common IDUA mutation, W402X. Notably, a new IDUA mutation was also identified in the proband, his sister and mother accounting for deficiency of IDUA activity in these individuals. The asymptomatic sister, who had normal glycosaminoglycan excretion, is a compound heterozygote for W402X and this new allele; we believe this new mutation is the first IDUA pseudodeficiency gene to be elucidated at the molecular level.

  16. Clinical and molecular delineation of Tetrasomy 9p syndrome: report of 12 new cases and literature review.

    Science.gov (United States)

    El Khattabi, Laïla; Jaillard, Sylvie; Andrieux, Joris; Pasquier, Laurent; Perrin, Laurence; Capri, Yline; Benmansour, Abdelmadjid; Toutain, Annick; Marcorelles, Pascale; Vincent-Delorme, Catherine; Journel, Hubert; Henry, Catherine; De Barace, Claire; Devisme, Louise; Dubourg, Christèle; Demurger, Florence; Lucas, Josette; Belaud-Rotureau, Marc-Antoine; Amiel, Jeanne; Malan, Valérie; De Blois, Marie-Christine; De Pontual, Loïc; Lebbar, Aziza; Le Dû, Nathalie; Germain, Dominique P; Pinard, Jean-Marc; Pipiras, Eva; Tabet, Anne-Claude; Aboura, Azzedine; Verloes, Alain

    2015-06-01

    Tetrasomy 9p is a generic term describing the presence of a supernumerary chromosome incorporating two copies of the 9p arm. Two varieties exist: isodicentric chromosome 9p (i(9p)), where the two 9p arms are linked by a single centromeric region, and pseudodicentric 9p (idic(9p)), where one active and one inactive centromere are linked together by a proximal segment of 9q that may incorporate euchromatic material. In living patients, i(9p) and idic(9p) are usually present in a mosaic state. Fifty-four cases, including fetuses, have been reported, of which only two have been molecularly characterized using array-CGH. Tetrasomy 9p leads to a variable phenotype ranging from multiple congenital anomalies with severe intellectual disability and growth delay to subnormal cognitive and physical developments. Hypertelorism, abnormal ears, microretrognathia and bulbous nose are the most common dysmorphic traits. Microcephaly, growth retardation, joint dislocation, scoliosis, cardiac and renal anomalies were reported in several cases. Those physical anomalies are often, but not universally, accompanied by intellectual disability. The most recurrent breakpoints, defined by conventional cytogenetics, are 9p10, 9q12 and 9q13. We report on 12 new patients with tetrasomy 9p (3 i(9p), 8 idic(9p) and one structurally uncharacterized), including the first case of parental germline mosaicism. All rearrangements have been characterized by DNA microarray. Based on our results and a review of the literature, we further delineate the prenatal and postnatal clinical spectrum of this imbalance. Our results show poor genotype-phenotype correlations and underline the need of precise molecular characterization of the supernumerary marker. PMID:25847481

  17. Modulation of the gut microbiota composition by rifaximin in non-constipated irritable bowel syndrome patients: a molecular approach

    Directory of Open Access Journals (Sweden)

    Soldi S

    2015-12-01

    Full Text Available Sara Soldi,1 Sotirios Vasileiadis,2 Francesca Uggeri,1 Mariachiara Campanale,3 Lorenzo Morelli,4 Maria Vittoria Fogli,5 Fiorella Calanni,5 Maria Grimaldi,5 Antonio Gasbarrini31AAT – Advanced Analytical Technologies Srl, Piacenza, Italy; 2Centre for Environmental Risk Assessment and Remediation, University of South Australia, Mawson Lakes, Australia; 3Internal Medicine and Gastroenterology Division, Catholic University of Rome, Rome, Italy; 4Microbiology Institute, Catholic University of Piacenza, Piacenza, Italy; 5Alfa Wassermann SpA, Bologna, ItalyAbstract: Rifaximin, with its low systemic absorption, may represent a treatment of choice for irritable bowel syndrome (IBS, mainly due to its ability to act on IBS pathogenesis, through the influence on gut microbiota. The aim of the present study was to assess, by biomolecular tools, the rifaximin active modulation exerted on gut microbiota of non-constipated IBS patients. Fifteen non-constipated IBS subjects were treated with 550 mg rifaximin three times a day for 14 days. Stool samples were collected before starting the treatment, at the end of it, and after a 6-week washout period. Real-time polymerase chain reaction, denaturing gradient gel electrophoresis, and next-generation sequencing were applied to all the samples to verify and quantify possible microbial fluctuations. Rifaximin treatment did not affect the overall composition of the microbiota of the treated subjects, inducing fluctuations in few bacterial groups, balanced by the replacement of homologs or complementary bacterial groups. Rifaximin appeared to influence mainly potentially detrimental bacteria, such as Clostridium, but increasing the presence of some species, such as Faecalibacterium prausnitzii. A decrease in the Firmicutes/Bacteroidetes ratio after 14 days of treatment and bacterial profiles with higher biodiversity were observed during the follow-up compared to baseline. Rifaximin treatment, although effective on IBS

  18. Noonan syndrome.

    Science.gov (United States)

    Bhambhani, Vikas; Muenke, Maximilian

    2014-01-01

    Noonan syndrome is a common genetic disorder that causes multiple congenital abnormalities and a large number of potential health conditions. Most affected individuals have characteristic facial features that evolve with age; a broad, webbed neck; increased bleeding tendency; and a high incidence of congenital heart disease, failure to thrive, short stature, feeding difficulties, sternal deformity, renal malformation, pubertal delay, cryptorchidism, developmental or behavioral problems, vision problems, hearing loss, and lymphedema. Familial recurrence is consistent with an autosomal dominant mode of inheritance, but most cases are due to de novo mutations. Diagnosis can be made on the basis of clinical features, but may be missed in mildly affected patients. Molecular genetic testing can confirm diagnosis in 70% of cases and has important implications for genetic counseling and management. Most patients with Noonan syndrome are intellectually normal as adults, but some may require multidisciplinary evaluation and regular follow-up care. Age-based Noonan syndrome-specific growth charts and treatment guidelines are available. PMID:24444506

  19. Molecular diagnosis of mucopolysaccharidosis Type II (Hunter syndrome) by automated sequencing and computer-assisted interpretation: Toward mutation mapping of the Iduronate-2-sulfatase gene

    Energy Technology Data Exchange (ETDEWEB)

    Jonsson, J.J.; Aronovich, E.L.; Braun, S.E.; Whitley, C.B. [Univ. of Minnesota Medical School, Minneapolis, MN (United States)

    1995-03-01

    Virtually all mutations causing Hunter syndrome (mucopolysaccharidosis type II) are expected to be new mutations. Therefore, as a means of molecular diagnosis, we developed a rapid method to sequence the entire iduronate-2-sulfatase (IDS) coding region. PCR amplicons representing the IDS cDNA were sequenced with an automatic instrument, and output was analyzed by computer-assisted interpretation of tracings, using Staden programs on a Sun computer. Mutations were found in 10 of 11 patients studied. Unique missense mutations were identified in five patients: H229Y (685{r_arrow}T, severe phenotype); P358R (1073C{r_arrow}G, severe); R468W (1402C{r_arrow}T, mild); P469H (1406C{r_arrow}A, mild); and Y523C (1568A{r_arrow}G, mild). Nonsense mutations were identified in two patients: R172X (514C{r_arrow}T, severe) and Q389X (1165C{r_arrow}T, severe). Two other patients with severe disease had insertions of 1 and 14 bp, in exons 3 and 6, respectively. In another patient with severe disease, the predominant (<95%) IDS message resulted from aberrant splicing, which skipped exon 3. In this last case, consensus sequences for splice sites in exon 3 were intact, but a 395C{r_arrow}G mutation was identified 24 bp upstream from the 3` splice of exon 3. This mutation created a cryptic 5` splice site with a better consensus sequence for 5` splice sites than the natural 5` splice site of intron 3. A minor population of the IDS message was processed by using this cryptic splice site; however, no correctly spliced message was detected in leukocytes from this patient. The mutational topology of the IDS gene is presented. 46 refs., 6 figs., 2 tabs.

  20. High-molecular-weight adiponectin is selectively reduced in women with polycystic ovary syndrome independent of body mass index and severity of insulin resistance.

    LENUS (Irish Health Repository)

    O'Connor, A

    2010-03-01

    Context: High-molecular-weight (HMW) adiponectin contributes to insulin resistance (IR), which is closely associated with the pathophysiology of polycystic ovary syndrome (PCOS). Abnormalities in adipocyte function have been identified in PCOS and potentially contribute to lower adiponectin concentrations. Objective: Our objective was to determine which variables in plasma and adipose tissue influence HMW adiponectin in a well characterized cohort of women with PCOS. Design: This was a cross-sectional study. Settings and Participants: A teaching hospital. Women with PCOS (n = 98) and body mass index (BMI)-matched controls (n = 103) (including 68 age-, BMI-, and IR-matched pairs). Interventions: A standard 75-g oral glucose tolerance test was performed for each participant. Subcutaneous adipose tissue samples were taken by needle biopsy for a subset of PCOS women (n = 9) and controls (n = 8). Main Outcome Measures: Serum levels of HMW adiponectin and their relation to indices of insulin sensitivity, body composition, and circulating androgens as well as adipose tissue expression levels of ADIPOQ, TNFalpha, PPARgamma, and AR were assessed. Results: HMW adiponectin was significantly lower in women with PCOS compared with both BMI- and BMI- and IR-matched controls (P = 0.009 and P = 0.027, respectively). Although BMI and IR were the main predictors of HMW adiponectin, an interaction between waist to hip ratio and plasma testosterone contributed to its variance (P = 0.026). Adipose tissue gene expression analysis demonstrated that AR and TNFalpha (P = 0.008 and P = 0.035, respectively) but not ADIPOQ mRNA levels were increased in PCOS compared with controls. Conclusions: HMW adiponectin is selectively reduced in women with PCOS, independent of BMI and IR. Gene expression analysis suggests that posttranscriptional\\/translational modification contributes to reduced HMW adiponectin in PCOS.

  1. The electrocardiographic paradox of tako-tsubo cardiomyopathy-comparison with acute ischemic syndromes and consideration of molecular biology and electrophysiology to understand the electrical-mechanical mismatching.

    Science.gov (United States)

    Sclarovsky, Samuel; Nikus, Kjell

    2010-01-01

    From the electrocardiographic (ECG) point of view, the tako-tsubo cardiomyopathy (TTC) behaves like an acute subepicardial circumferential ischemic syndrome. The electrical manifestations are significantly different from those of acute transmural segmental ischemia, in which the ECG primarily expresses the electrophysiologic and metabolic changes occurring in the subepicardial layer. In comparison with transmural anterior ischemia and despite acute contraction impairment (circumferential middle and apical dyskinesis and basal hyperkinesis), in TTC there is typically only moderate ST elevation in the precordial leads. This paradox can be understood by taking into consideration the molecular biology and basic electrophysiology. In the senescent female with hypoestrogenemia, the subepicardium is almost totally unprotected against "adrenergic storm." In the fertile female, estrogen plays the pivotal role of protecting the myocardium at many levels of the metabolic cascade, such as in the regulation of the presynaptic release of adrenergic substances and by increasing the release of adenosine. There is consequential increase of the adenosine triphosphate (ATP)-sensitive K+ channels, thus regulating the inward flow of Ca2+ toward the sarcoplasmic reticulum. The ATP-sensitive K+ channels hyperpolarize the subepicardial cells during extremely aggressive situations such as ischemia and adrenergic storm. The hyperpolarization of the subepicardium is manifested in the ECG by tall, peaked T waves, indicating an increase of the repolarization gradient between the subendocardial and subepicardial layers. In the absence of estrogen, there are severe decreases in the concentration of adenosine and in the density of the ATP-sensitive K+ channels. The subepicardial myocytes cannot be hyperpolarized, and the adrenergic storm is manifested by moderate ST-T elevation. Furthermore, the very rapid appearance and disappearance of a Q wave are "against the rules." This is a classical

  2. Molecular characterisation of the 22q13 deletion syndrome supports the role of haploinsufficiency of SHANK3/PROSAP2 in the major neurological symptoms

    OpenAIRE

    Wilson, H.; Wong, A; Shaw, S.; Tse, W; Stapleton, G; Phelan, M; Hu, S.; Marshall, J; McDermid, H

    2003-01-01

    Methods: The 22q13 deletion syndrome (MIM 606232) is characterised by moderate to profound mental retardation, delay/absence of expressive speech, hypotonia, normal to accelerated growth, and mild dysmorphic features. We have determined the deletion size and parent of origin in 56 patients with this syndrome.

  3. Joubert Syndrome

    Science.gov (United States)

    ... Awards Enhancing Diversity Find People About NINDS NINDS Joubert Syndrome Information Page Table of Contents (click to ... Organizations Related NINDS Publications and Information What is Joubert Syndrome? Joubert syndrome is a rare brain malformation ...

  4. Marfan Syndrome

    Science.gov (United States)

    Marfan syndrome is a disorder that affects connective tissue. Connective tissues are proteins that support skin, bones, ... fibrillin. A problem with the fibrillin gene causes Marfan syndrome. Marfan syndrome can be mild to severe, ...

  5. Genetics Home Reference: genitopatellar syndrome

    Science.gov (United States)

    ... syndrome have distinct clinical features reflecting distinct molecular mechanisms. Hum Mutat. 2012 Nov;33(11):1520-5. ... with a qualified healthcare professional . About Genetics Home Reference Site Map Contact Us Selection Criteria for Links ...

  6. ANTICOAGULANTS IN ACUTE CORONARY SYNDROME

    OpenAIRE

    I. A. Latfullin; A. A. Podolskaya

    2016-01-01

    Clinical efficacy of unfractionated and low molecular heparins in acute coronary syndrome is discussed. New synthetic heparin derivative fondaparinux (Arixtra) is focused. Author’s brief experience of fondaparinux clinical implementation is presented.

  7. Two Likely Pathogenic Variants of COL2A1 in Unrelated Korean Patients With Ocular-Only Variants of Stickler Syndrome: The First Molecular Diagnosis in Korea

    OpenAIRE

    Yoon, Je Moon; Jang, Mi-Ae; Ki, Chang-Seok; Kim, Sang Jin

    2015-01-01

    Stickler syndrome is a genetically heterogeneous disorder that affects the ocular, auditory, and musculoskeletal systems. Ocular-only variant of Stickler syndrome type 1 (OSTL1) is characterized by high risk of retinal detachment without systemic involvement and is caused by alternatively spliced exon 2 mutation of COL2A1. We report the cases of two Korean families with OSTL1 carrying likely pathogenic variants of COL2A1. All patients presented with membranous vitreous anomaly, peripheral ret...

  8. Molecular breakpoint cloning and gene expression studies of a novel translocation t(4;15(q27;q11.2 associated with Prader-Willi syndrome

    Directory of Open Access Journals (Sweden)

    Slater Howard R

    2005-05-01

    Full Text Available Abstract Background Prader-Willi syndrome (MIM #176270; PWS is caused by lack of the paternally-derived copies, or their expression, of multiple genes in a 4 Mb region on chromosome 15q11.2. Known mechanisms include large deletions, maternal uniparental disomy or mutations involving the imprinting center. De novo balanced reciprocal translocations in 5 reported individuals had breakpoints clustering in SNRPN intron 2 or exon 20/intron 20. To further dissect the PWS phenotype and define the minimal critical region for PWS features, we have studied a 22 year old male with a milder PWS phenotype and a de novo translocation t(4;15(q27;q11.2. Methods We used metaphase FISH to narrow the breakpoint region and molecular analyses to map the breakpoints on both chromosomes at the nucleotide level. The expression of genes on chromosome 15 on both sides of the breakpoint was determined by RT-PCR analyses. Results Pertinent clinical features include neonatal hypotonia with feeding difficulties, hypogonadism, short stature, late-onset obesity, learning difficulties, abnormal social behavior and marked tolerance to pain, as well as sticky saliva and narcolepsy. Relative macrocephaly and facial features are not typical for PWS. The translocation breakpoints were identified within SNRPN intron 17 and intron 10 of a spliced non-coding transcript in band 4q27. LINE and SINE sequences at the exchange points may have contributed to the translocation event. By RT-PCR of lymphoblasts and fibroblasts, we find that upstream SNURF/SNRPN exons and snoRNAs HBII-437 and HBII-13 are expressed, but the downstream snoRNAs PWCR1/HBII-85 and HBII-438A/B snoRNAs are not. Conclusion As part of the PWCR1/HBII-85 snoRNA cluster is highly conserved between human and mice, while no copy of HBII-438 has been found in mouse, we conclude that PWCR1/HBII-85 snoRNAs is likely to play a major role in the PWS- phenotype.

  9. Rett syndrome: clinical and molecular characterization of two Brazilian patients Síndrome de Rett: caracterização clínica e molecular de dois casos brasileiros

    Directory of Open Access Journals (Sweden)

    Andrea Stachon

    2007-03-01

    Full Text Available BACKGROUND: Rett syndrome (RS is recognized as a pan-ethnic condition. Since the identification of mutations in the MECP2 gene, more patients have been diagnosed, and a broad spectrum of phenotypes has been reported. There is a lack of phenotype-genotype studies. OBJECTIVE: To describe two cases of Brazilian patients with identified MECP2 mutations. METHOD: We present two female Brazilian patients with RS. RESULTS: Both patients presented with regression at 2-3 years of age, when stereotypic hand movements, social withdrawal and postnatal deceleration of head growth rate were observed. Both patients presented verbal communication impairment. Case 1 had loss of purposeful hand movements, and severe seizure episodes. Case 2 had milder impairment of purposeful hand movements, and no seizures. They had different mutations, D97Y and R294X, found in exons 3 and 4 of MECP2 gene, respectively. CONCLUSION: Testing for MECP2 mutations is important to confirm diagnosis and to establish genotype/phenotype correlations, and improve genetic counseling.CONTEXTO: Síndrome de Rett (RS é doença pan-étnica de fenótipo bastante variado desde que foram identificadas mutações no gene MECP2 e um número maior de pacientes tem sido diagnosticadas. Existe uma demanda por estudos que investiguem a relação genótipo-fenotipo. OBJETIVO: Descrever dois casos brasileiros de RS com mutações identificadas. MÉTODO: Duas pacientes brasileiras com diagnóstico clínico-molecular de RS foram descritas buscando-se correlacionar genótipo-fenótipo. RESULTADOS: Ambas pacientes apresentaram regressão aos 2-3 anos de idade, movimentos esteriotipados de mãos, retraimento social e desaceleração do crescimento encefálico. Ambas apresentaram déficit de comunicação verbal. Caso 1 também apresentou perda dos movimentos manuais intencionados e crises convulsivas graves. Caso 2 apresentou-se com comprometimento parcial dos movimentos manuais e sem história de crise

  10. Kindler syndrome

    Directory of Open Access Journals (Sweden)

    Kaviarasan P

    2005-01-01

    Full Text Available Kindler syndrome is a rare autosomal recessive disorder associated with skin fragility. It is characterized by blistering in infancy, photosensitivity and progressive poikiloderma. The syndrome involves the skin and mucous membrane with radiological changes. The genetic defect has been identified on the short arm of chromosome 20. This report describes an 18-year-old patient with classical features like blistering and photosensitivity in childhood and the subsequent development of poikiloderma. The differential diagnosis of Kindler syndrome includes diseases like Bloom syndrome, Cockayne syndrome, dyskeratosis congenita, epidermolysis bullosa, Rothmund-Thomson syndrome and xeroderma pigmentosum. Our patient had classical cutaneous features of Kindler syndrome with phimosis as a complication.

  11. Targeted therapy for genetic cancer syndromes: Von Hippel-Lindau disease, Cowden syndrome, and Proteus syndrome.

    Science.gov (United States)

    Agarwal, Rishi; Liebe, Sarah; Turski, Michelle L; Vidwans, Smruti J; Janku, Filip; Garrido-Laguna, Ignacio; Munoz, Javier; Schwab, Richard; Rodon, Jordi; Kurzrock, Razelle; Subbiah, Vivek

    2015-02-01

    Von Hippel-Lindau disease, Cowden syndrome, and Proteus syndrome are cancer syndromes which affect multiple organs and lead to significant decline in quality of life in affected patients. These syndromes are rare and typically affect the adolescent and young adult population, resulting in greater cumulative years of life lost. Improved understanding of the underpinnings of the genetic pathways underlying these syndromes and the rapid evolution of targeted therapies in general have made it possible to develop therapeutic options for these patients and other genetic cancer syndromes. Targeted therapies especially antiangiogenics and inhibitors of the PIK3CA/AKT/mTOR signaling pathway have shown activity in selected group of patients affected by these syndromes or in patients harboring specific sporadic mutations which are otherwise characteristic of these syndromes. Unfortunately due to the rare nature, patients with these syndromes are not the focus of clinical trials and unique results seen in these patients can easily go unnoticed. Most of the data suggesting benefits of targeted therapies are either case reports or small case series. Thus, a literature review was indicated. In this review we explore the use of molecularly targeted therapy options in Von Hippel-Lindau disease, Cowden syndrome, and Proteus syndrome. PMID:25725225

  12. Clinical, cytogenetic and molecular analysis of androgen insensitivity syndromes from south Indian cohort and detection and in-silico characterization of androgen receptor gene mutations.

    Science.gov (United States)

    V G, Abilash; S, Radha; K M, Marimuthu; K, Thangaraj; S, Arun; S, Nishu; A, Mohana Priya; J, Meena; D, Anuradha

    2016-01-30

    Rare cases of 9 complete androgen insensitivity syndromes, 9 cases of partial androgen insensitivity syndromes and equal number of male control samples were selected for this study. Few strong variations in clinical features were noticed; Giemsa banded metaphase revealed a 46,XY karyotype and the frequency of chromosome aberrations were significantly higher when compared with control samples. DNA sequence analysis of the androgen receptor gene of androgen insensitivity syndromes revealed three missense mutations - c.C1713>G resulting in the replacement of a highly conserved histidine residue with glutamine p.(His571Glu) in DNA-binding domain, c.A1715>G resulting in the replacement of a highly conserved tyrosine residue with cysteine p.(Tyr572Cys) in DNA-binding domain and c.G2599>A resulting in the replacement of a highly conserved valine residue with methionine p.(Val867Met) in ligand-binding domain of androgen receptor gene respectively. The heterozygous type of mutations c.C1713>G and c.G2599>A observed in mothers of the patients for familial cases concluding that the mutation was inherited from the mother. The novel mutation c.C1713>G is reported first time in androgen insensitivity syndrome. In-silico analysis of mutations observed in androgen receptor gene of androgen insensitivity syndrome predicted that the substitution at Y572C and V867M could probably disrupt the protein structure and function. PMID:26688387

  13. Clinical and molecular analysis of two Chinese siblings with Cockayne syndrome%Cockayne综合征两例临床特征与基因突变分析

    Institute of Scientific and Technical Information of China (English)

    周知子; 刘丽; 吴莫龄; 刘鸿圣; 蔡燕娜; 盛慧英; 李秀珍; 程静; 李端

    2016-01-01

    目的 分析Cockayne综合征患儿临床特征及基因突变.方法 分析归纳2013年7月至2014年11月广州妇女儿童医疗中心收治的一对同胞兄弟共患经典型Cockayne综合征的临床特点;提取患儿及其血缘父母外周血全基因组DNA,用PCR方法扩增ERCC6基因全部外显子及与其相连的内含子区,扩增产物行双向测序,查找突变位点.结果 患儿为同胞两兄弟,分别为4岁8月龄和7岁5月龄.均因"生长和智力落后数年"就诊,母孕产史均无异常.1岁前,患儿身高、体重均在正常范围内.1岁半后均出现身高、体重增长缓慢,运动发育落后,眼、皮肤光敏感,听力及视神经损害,小头、眼窝深邃.例1(先证者)就诊时身高90.8 cm,体重9.1kg,头围41 cm,胸围44 cm;例2(先证者胞兄)就诊时身高92 cm,体重11.2 kg,头围41 cm,胸围46 cm.例1在4岁半,例2在7岁时头颅MRI检查提示全脑萎缩,脑室扩大,髓鞘形成不良.头颅磁共振波谱分析(氢谱)-MR成像提示左右两侧背侧丘脑、岛叶及左侧半卵圆中心神经元损伤.头颅CT提示双侧基底节对称性钙化.ERCC6基因突变分析提示兄弟俩ERCC6基因均存在c.1357C>T(p.Arg453Ter)与c.1607T>G(p.Leu536Trp)复合杂合致病突变,突变分别遗传自患儿母亲和父亲.结论 Cockayne综合征患儿具有出生时正常,生后逐渐出现生长发育迟缓,语言、智力落后,脑损伤、小头畸形,眼窝深邃,皮肤光敏感等临床特征,存在ERCC6基因突变,易误诊为脑瘫、先天性小头畸形等.%Objective Cockayne syndrome is a rare disease and difficult to be recognized.This study aimed to expand the knowledge of the clinical and molecular characteristics of the children with Cockayne syndrome (CS).Method Clinical data of two siblings with classic CS of Guangzhou Women and Children's Medical Center from July 2013 to November 2014 were obtained and analyzed.The whole DNA of peripheral blood was collected from two CS siblings and

  14. Molecular characterization of a heterothallic mating system in .i.Pseudogymnoascus destructans./i., the fungus causing white-nose syndrome of bats

    Czech Academy of Sciences Publication Activity Database

    Palmer, J.M.; Kubátová, A.; Nováková, Alena; Minnis, A.M.; Kolařík, M.; Lindner, D.L.

    2014-01-01

    Roč. 4, č. 9 (2014), s. 1755-1763. ISSN 2160-1836 Institutional support: RVO:60077344 Keywords : Genetics of Sex * geomyces * mating type * sexual reproduction * white-nose syndrome Subject RIV: EE - Microbiology, Virology Impact factor: 3.198, year: 2014

  15. Molecular Screening of "MECP2" Gene in a Cohort of Lebanese Patients Suspected with Rett Syndrome: Report on a Mild Case with a Novel Indel Mutation

    Science.gov (United States)

    Corbani, S.; Chouery, E.; Fayyad, J.; Fawaz, A.; El Tourjuman, O.; Badens, C.; Lacoste, C.; Delague, V.; Megarbane, A.

    2012-01-01

    Background: Rett syndrome (RTT), an X-linked, dominant, neurodevelopment disorder represents 10% of female subjects with profound intellectual disability. Mutations in the "MECP2" gene are responsible for up to 95% of the classical RTT cases, and nearly 500 different mutations distributed throughout the gene have been reported. Methods: We report…

  16. The pathogenesis of foot-and-mouth disease II; viral pathways in swine, small ruminants, and wildlife, myotropism, chronic syndromes, and molecular virus-host interactions

    Science.gov (United States)

    Investigation of the pathogenesis of foot-and-mouth disease (FMD) has focused on study of the disease in cattle with less emphasis on pigs, small ruminants, and wildlife. “Atypical” FMD-associated syndromes such as myocarditis, reproductive losses, and chronic heat-intolerance have also received lit...

  17. 46,XX Male Syndrome

    Directory of Open Access Journals (Sweden)

    Bekir Uçan

    2013-06-01

    Full Text Available 46, XX male syndrome – testicular disorder of sexual differentiation (DSD is a rare condition characterized by a spectrum of clinical presentations, ranging from ambiguous to normal male genitalia. These cases are diagnosed more easily in childhood. In adults, the diagnosis can be difficult due to the current normal gender development. Here, we report hormonal, molecular and cytogenetic results in an adult male patient with primary hypogonadism who was diagnosed with 46, XX male syndrome in our clinic. Turk Jem 2013; 17: 46-8

  18. Cushing's Syndrome

    Science.gov (United States)

    ... Cushing's syndrome, also called hypercortisolism , is a rare endocrine disorder caused by chronic exposure of the body's tissues ... removing the tumor while minimizing the chance of endocrine deficiency or long-term ... for Cushing's Syndrome Clinical Trials ...

  19. Turner Syndrome

    Science.gov (United States)

    Turner syndrome is a genetic disorder that affects a girl's development. The cause is a missing or incomplete ... t work properly. Other physical features typical of Turner syndrome are Short, "webbed" neck with folds of skin ...

  20. Metabolic Syndrome

    Science.gov (United States)

    Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These ... doctors agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

  1. Asperger syndrome

    Science.gov (United States)

    Asperger syndrome is often considered a high functioning form of autism. It can lead to difficulty interacting socially, repeat behaviors, and clumsiness. Asperger syndrome is a part of the larger developmental disorder ...

  2. Pseudoaminopterin syndrome.

    Science.gov (United States)

    Kraoua, Lilia; Capri, Yline; Perrin, Laurence; Benmansour, Abdelmajjid; Verloes, Alain

    2012-09-01

    Pseudoaminopterin syndrome or aminopterin syndrome-like sine aminopterin (ASSA syndrome--OMIM 600325] is a rare autosomal recessive syndrome defined by characteristic dysmorphic features, skeletal defects, limb anomalies, cryptorchidism, and growth retardation. The syndrome owes its name to the fact that patients resemble the children exposed to aminopterin or to methotrexate, two dihydrofolate reductase inhibitors used for chemotherapy, or as an abortificient in early pregnancy. Ten patients have been described with pseudoaminopterin syndrome. Their phenotype is variable, and differs from the phenotype resulting from folic acid deprivation, leading to the notion that the pathogenesis may be more complex than simple vitamin deficiency. We report on an Algerian patient with pseudoaminopterin syndrome, review the previously reported cases and confirm that pseudoaminopterin syndrome does not result from a detectable contiguous gene imbalance as high resolution CGH array was normal in this child. PMID:22811276

  3. Usher Syndrome

    Science.gov (United States)

    Usher syndrome is an inherited disease that causes serious hearing loss and retinitis pigmentosa, an eye disorder ... hearing and vision. There are three types of Usher syndrome: People with type I are deaf from ...

  4. Turner Syndrome

    Science.gov (United States)

    Turner syndrome is a genetic disorder that affects a girl's development. The cause is a missing or ... t work properly. Other physical features typical of Turner syndrome are Short, "webbed" neck with folds of ...

  5. Proteus Syndrome

    Science.gov (United States)

    ... Gift Stock Gift Sunshine Society Contact Privacy Policy Proteus Syndrome Definition Common Signs Diagnostic Criteria (I have ... NIH to go with this criteria) Glossary Videos Proteus Syndrome is a condition which involves atypical growth ...

  6. Learning about Marfan Syndrome

    Science.gov (United States)

    ... genetic terms used on this page Learning About Marfan Syndrome What is Marfan syndrome? What are the ... Syndrome Additional Resources for Marfan Syndrome What is Marfan syndrome? Marfan syndrome is one of the most ...

  7. Alagille syndrome.

    OpenAIRE

    Krantz, I D; Piccoli, D A; Spinner, N B

    1997-01-01

    Alagille syndrome (OMIM 118450) is an autosomal dominant disorder associated with abnormalities of the liver, heart, eye, skeleton, and a characteristic facial appearance. Also referred to as the Alagille-Watson syndrome, syndromic bile duct paucity, and arteriohepatic dysplasia, it is a significant cause of neonatal jaundice and cholestasis in older children. In the fully expressed syndrome, affected subjects have intrahepatic bile duct paucity and cholestasis, in conjunction with cardiac ma...

  8. The Greig cephalopolysyndactyly syndrome

    Directory of Open Access Journals (Sweden)

    Biesecker Leslie G

    2008-04-01

    Full Text Available Abstract The Greig cephalopolysyndactyly syndrome (GCPS is a pleiotropic, multiple congenital anomaly syndrome. It is rare, but precise estimates of incidence are difficult to determine, as ascertainment is erratic (estimated range 1–9/1,000,000. The primary findings include hypertelorism, macrocephaly with frontal bossing, and polysyndactyly. The polydactyly is most commonly preaxial of the feet and postaxial in the hands, with variable cutaneous syndactyly, but the limb findings vary significantly. Other low frequency findings include central nervous system (CNS anomalies, hernias, and cognitive impairment. GCPS is caused by loss of function mutations in the GLI3 transcription factor gene and is inherited in an autosomal dominant pattern. The disorder is allelic to the Pallister-Hall syndrome and one form of the acrocallosal syndrome. Clinical diagnosis is challenging because the findings of GCPS are relatively non-specific, and no specific and sensitive clinical have been delineated. For this reason, we have proposed a combined clinical-molecular definition for the syndrome. A presumptive diagnosis of GCPS can be made if the patient has the classic triad of preaxial polydactyly with cutaneous syndactyly of at least one limb, hypertelorism, and macrocephaly. Patients with a phenotype consistent with GCPS (but which may not manifest all three attributes listed above and a GLI3 mutation may be diagnosed definitively with GCPS. In addition, persons with a GCPS-consistent phenotype who are related to a definitively diagnosed family member in a pattern consistent with autosomal dominant inheritance may be diagnosed definitively as well. Antenatal molecular diagnosis is technically straightforward to perform. Differential diagnoses include preaxial polydactyly type 4, the GCPS contiguous gene syndrome, acrocallosal syndrome, Gorlin syndrome, Carpenter syndrome, and Teebi syndrome. Treatment of the disorder is symptomatic, with plastic or

  9. Cushing Syndrome

    Science.gov (United States)

    ... links Share this: Page Content What is Cushing’s syndrome? Cushing’s syndrome is a condition that occurs when the body’s ... medication or as a result of a tumor, Cushing’s syndrome can develop. Many factors influence whether this happens, ...

  10. Dumping Syndrome

    Science.gov (United States)

    ... Disease Organizations​​ (PDF, 341 KB)​​​​​ Alternate Language URL Dumping Syndrome Page Content On this page: What is ... Nutrition Points to Remember Clinical Trials What is dumping syndrome? Dumping syndrome occurs when food, especially sugar, ...

  11. Molecular Study of Three Lebanese and Syrian Patients with Waardenburg Syndrome and Report of Novel Mutations in the EDNRB and MITF Genes

    OpenAIRE

    Haddad, N M; Ente, D.; Chouery, E.; Jalkh, N.; Mehawej, C.; Khoueir, Z; PINGAULT, V.; Mégarbané, A.

    2011-01-01

    Waardenburg syndrome (WS) is a genetic disorder characterized primarily by depigmentation of the skin and hair, heterochromia of the irides, sensorineural deafness, and sometimes by dystopia canthorum, and Hirschsprung disease. WS presents a large clinical and genetic heterogeneity. Four different types have been individualized and linked to 5 different genes. We report 2 cases of WS type II and 1 case of WS type IV from Lebanon and Syria. The genetic studies revealed 2 novel mutations in the...

  12. Analysis of Disease Progression-Associated Gene Expression Profile in Fibrillin-1 Mutant Mice: New Insight into Molecular Pathogenesis of Marfan Syndrome

    OpenAIRE

    Kim, Koung Li; Choi, Chanmi; Suh, Wonhee

    2014-01-01

    Marfan syndrome (MFS) is a dominantly inherited connective tissue disorder caused by mutations in the gene encoding fibrillin-1 (FBN1) and is characterized by aortic dilatation and dissection, which is the primary cause of death in untreated MFS patients. However, disease progression-associated changes in gene expression in the aortic lesions of MFS patients remained unknown. Using a mouse model of MFS, FBN1 hypomorphic mouse (mgR/mgR), we characterized the aortic gene expression profiles dur...

  13. Molecular linkage of hantavirus pulmonary syndrome to the white-footed mouse, Peromyscus leucopus: genetic characterization of the M genome of New York virus.

    OpenAIRE

    Hjelle, B; Lee, S. W.; Song, W.; Torrez-Martinez, N; Song, J. W.; Yanagihara, R; Gavrilovskaya, I; Mackow, E R

    1995-01-01

    The complete M segment sequences of hantaviruses amplified from tissues of a patient with hantavirus pulmonary syndrome in the northeastern United States and from white-footed mice, Peromyscus leucopus, from New York were 99% identical and differed from those of Four Corners virus by 23%. The serum of this patient failed to recognize a conserved, immunodominant epitope of the Four Corners virus G1 glycoprotein. Collectively, these findings indicate that P. leucopus harbors a genetically and a...

  14. Molecular signature of adipose tissue in patients with both Non-Alcoholic Fatty Liver Disease (NAFLD) and Polycystic Ovarian Syndrome (PCOS)

    OpenAIRE

    Baranova, Ancha; Tran, Thuy Phuong; Afendy, Arian; Wang, Lei; Shamsaddini, Amirhossein; Mehta, Rohini; Chandhoke, Vikas; Birerdinc, Aybike; Younossi, Zobair M.

    2013-01-01

    Background Polycystic ovarian syndrome (PCOS) is one of the most common reproductive disorders with strong association with both insulin resistance and non-alcoholic fatty liver disease (NAFLD). To untangle the complex relationship between PCOS and NAFLD, we analyzed serum biomarkers of apoptosis, some adipokines and mRNA profiles in the visceral adipose tissue of obese patients with NAFLD who were also diagnosed with PCOS and compared to a group with NAFLD only. Methods We included patients ...

  15. Clinical and molecular characterization of 40 patients with classic Ehlers–Danlos syndrome: identification of 18 COL5A1 and 2 COL5A2 novel mutations

    OpenAIRE

    Ritelli, Marco; Dordoni, Chiara; Venturini, Marina; Chiarelli, Nicola; Quinzani, Stefano; Traversa, Michele; Zoppi, Nicoletta; Vascellaro, Annalisa; Wischmeijer, Anita; Manfredini, Emanuela; Garavelli, Livia; Calzavara-Pinton, Piergiacomo; Colombi, Marina

    2013-01-01

    Background Classic Ehlers–Danlos syndrome (cEDS) is a rare autosomal dominant connective tissue disorder that is primarily characterized by skin hyperextensibility, abnormal wound healing/atrophic scars, and joint hypermobility. A recent study demonstrated that more than 90% of patients who satisfy all of these major criteria harbor a type V collagen (COLLV) defect. Methods This cohort included 40 patients with cEDS who were clinically diagnosed according to the Villefranche nosology. The flo...

  16. Mutation in type II procollagen (COL2A1) that substitutes aspartate for glycine alpha 1-67 and that causes cataracts and retinal detachment: evidence for molecular heterogeneity in the Wagner syndrome and the Stickler syndrome (arthro-ophthalmopathy)

    OpenAIRE

    Körkkö, J; Ritvaniemi, P; Haataja, L; Kääriäinen, H; Kivirikko, K I; Prockop, D J; Ala-Kokko, L

    1993-01-01

    A search for mutations in the gene for type II procollagen (COL2A1) was carried out in affected members of a family with early-onset cataracts, lattice degeneration of the retina, and retinal detachment. They had no symptoms suggestive of involvement of nonocular tissues, as is typically found in the Stickler syndrome. The COL2A1 gene was amplified with PCR, and the products were analyzed by denaturing gradient gel electrophoresis. The results suggested a mutation in one allele for exon 10. S...

  17. Avian influenza virus, Streptococcus suis serotype 2, severe acute respiratory syndrome-coronavirus and beyond: molecular epidemiology, ecology and the situation in China.

    Science.gov (United States)

    Ma, Ying; Feng, Youjun; Liu, Di; Gao, George F

    2009-09-27

    The outbreak and spread of severe acute respiratory syndrome-associated coronavirus and the subsequent identification of its animal origin study have heightened the world's awareness of animal-borne or zoonotic pathogens. In addition to SARS, the highly pathogenic avian influenza virus (AIV), H5N1, and the lower pathogenicity H9N2 AIV have expanded their host ranges to infect human beings and other mammalian species as well as birds. Even the 'well-known' reservoir animals for influenza virus, migratory birds, became victims of the highly pathogenic H5N1 virus. Not only the viruses, but bacteria can also expand their host range: a new disease, streptococcal toxic shock syndrome, caused by human Streptococcus suis serotype 2 infection, has been observed in China with 52 human fatalities in two separate outbreaks (1998 and 2005, respectively). Additionally, enterohaemorrhagic Escherichia coli O157:H7 infection has increased worldwide with severe disease. Several outbreaks and sporadic isolations of this pathogen in China have made it an important target for disease control. A new highly pathogenic variant of porcine reproductive and respiratory syndrome virus (PRRSV) has been isolated in both China and Vietnam recently; although PRRSV is not a zoonotic human pathogen, its severe outbreaks have implications for food safety. All of these pathogens occur in Southeast Asia, including China, with severe consequences; therefore, we discuss the issues in this article by addressing the situation of the zoonotic threat in China. PMID:19687041

  18. Striatal neurodevelopment is dysregulated in purine metabolism deficiency and impacts DARPP-32, BDNF/TrkB expression and signaling: new insights on the molecular and cellular basis of Lesch-Nyhan Syndrome.

    Directory of Open Access Journals (Sweden)

    Ghiabe-Henri Guibinga

    Full Text Available Lesch-Nyhan Syndrome (LNS is a neurodevelopmental disorder caused by mutations in the gene encoding the purine metabolic enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT. This syndrome is characterized by an array of severe neurological impairments that in part originate from striatal dysfunctions. However, the molecular and cellular mechanisms underlying these dysfunctions remain largely unidentified. In this report, we demonstrate that HPRT-deficiency causes dysregulated expression of key genes essential for striatal patterning, most notably the striatally-enriched transcription factor B-cell leukemia 11b (Bcl11b. The data also reveal that the down-regulated expression of Bcl11b in HPRT-deficient immortalized mouse striatal (STHdh neural stem cells is accompanied by aberrant expression of some of its transcriptional partners and other striatally-enriched genes, including the gene encoding dopamine- and cAMP-regulated phosphoprotein 32, (DARPP-32. Furthermore, we demonstrate that components of the BDNF/TrkB signaling, a known activator of DARPP-32 striatal expression and effector of Bcl11b transcriptional activation are markedly increased in HPRT-deficient cells and in the striatum of HPRT knockout mouse. Consequently, the HPRT-deficient cells display superior protection against reactive oxygen species (ROS-mediated cell death upon exposure to hydrogen peroxide. These findings suggest that the purine metabolic defect caused by HPRT-deficiency, while it may provide neuroprotection to striatal neurons, affects key genes and signaling pathways that may underlie the neuropathogenesis of LNS.

  19. A molecular clock dates the common ancestor of European-type porcine reproductive and respiratory syndrome virus at more than 10 years before the emergence of disease

    DEFF Research Database (Denmark)

    Forsberg, Roald; Oleksiewicz, Martin B.; Krabbe Petersen, Anne Mette; Hein, Jotun; Bøtner, Anette; Storgaard, Torben

    2001-01-01

    The disease caused by porcine reproductive and respiratory syndrome virus (PRRSV) emerged independently and almost simultaneously in Europe (1990) and North America (1987). The original reservoir of the virus and the date it entered the pig populations is not known. In this study, we demonstrate an...... conclude that PRRSV virus most likely entered the pig population some time before the epidemic emergence of the virus, and hence, that emergence of European-type PRRSV is not the result of a recent species transmission event. Together, our results show that ORF3 sequencing is a valuable epidemiologic tool...

  20. Molecular Characterization of Transcriptome-wide Interactions between Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Porcine Alveolar Macrophages in vivo

    Directory of Open Access Journals (Sweden)

    Ping Zhou, Shanli Zhai, Xiang Zhou, Ping Lin, Tengfei Jiang, Xueying Hu, Yunbo Jiang, Bin Wu, Qingde Zhang, Xuewen Xu, Jin-ping Li, Bang Liu

    2011-01-01

    Full Text Available Porcine reproductive and respiratory syndrome virus (PRRSV infects mainly the porcine alveolar macrophages (PAMs and causes porcine reproductive and respiratory syndrome (PRRS. Previous studies have analyzed the global gene expression profiles of lung tissue in vivo and PAMs in vitro following infection with PRRSV, however, transcriptome-wide understanding of the interaction between highly pathogenic PRRSV (HP-PRRSV and PAMs in vivo has not yet been established. In this study, we employed Affymetrix microarrays to investigate the gene expression patterns of PAMs isolated from Tongcheng piglets (a Chinese indigenous breed after infection with HP-PRRSV. During the infection, Tongcheng piglets exhibited typical clinical signs, e.g. fever, asthma, coughing, anorexia, lethargy and convulsion, but displayed mild regional lung damage at 5 and 7 dpi. Microarray analysis revealed that HP-PRRSV infection has affected PAMs in expression of the important genes involved in cytoskeleton and exocytosis organization, protein degradation and folding, intracellular calcium and zinc homeostasis. Several potential antiviral strategies might be employed in PAMs, including upregulating IFN-induced genes and increasing intracellular zinc ion concentration. And inhibition of the complement system likely attenuated the lung damage during HP-PRRSV infection. Transcriptomic analysis of PAMs in vivo could lead to a better understanding of the HP-PRRSV-host interaction, and to the identification of novel antiviral therapies and genetic components of swine tolerance/susceptibility to HP-PRRS.

  1. Urinary Metabolomics Identifies a Molecular Correlate of Interstitial Cystitis/Bladder Pain Syndrome in a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP Research Network Cohort

    Directory of Open Access Journals (Sweden)

    Kaveri S. Parker

    2016-05-01

    Full Text Available Interstitial cystitis/bladder pain syndrome (IC/BPS is a poorly understood syndrome affecting up to 6.5% of adult women in the U.S. The lack of broadly accepted objective laboratory markers for this condition hampers efforts to diagnose and treat this condition. To identify biochemical markers for IC/BPS, we applied mass spectrometry-based global metabolite profiling to urine specimens from a cohort of female IC/BPS subjects from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP Research Network. These analyses identified multiple metabolites capable of discriminating IC/BPS and control subjects. Of these candidate markers, etiocholan-3α-ol-17-one sulfate (Etio-S, a sulfoconjugated 5-β reduced isomer of testosterone, distinguished female IC/BPS and control subjects with a sensitivity and specificity >90%. Among IC/BPS subjects, urinary Etio-S levels are correlated with elevated symptom scores (symptoms, pelvic pain, and number of painful body sites and could resolve high- from low-symptom IC/BPS subgroups. Etio-S-associated biochemical changes persisted through 3–6 months of longitudinal follow up. These results raise the possibility that an underlying biochemical abnormality contributes to symptoms in patients with severe IC/BPS.

  2. Isolation, Characterization, and Molecular Modeling of a Rheumatoid Factor from a Hepatitis C Virus Infected Patient with Sjögren’s Syndrome

    Directory of Open Access Journals (Sweden)

    Yu-Ching Lee

    2013-01-01

    Full Text Available We have previously isolated several IgG rheumatoid factors (RFs from patients with both rheumatoid arthritis and idiopathic thrombocytopenia purpura using phage display system. To study IgG RFs in patients with other autoimmune diseases, phage display antibody libraries from a hepatitis C virus infected patient with Sjögren’s syndrome were constructed. After panning, a specific clone RFL11 was isolated for characterization in advance. The binding activity and specificity of RFL11 to IgG Fc fragment were comparable to those of RFs previously isolated. The analysis with existed RF-Fc complex structures indicated the homology model of RFL11 is similar to IgM RF61 complex with high binding affinity of about 6×10-8 M. This effect resulted from longer complementarity-determining region (CDR combining key somatic mutations. In the RFL11-Fc interfaces, the CDR-H3 loop forms a finger-like structure extending into the bottom of Fc pocket and resulting in strong ion and cation-pi interactions. Moreover, a process of antigen-driven maturation was proven by somatically mutated VH residues on H2 and H3 CDR loops in the interfaces. Taken together, these results suggested that high affinity IgG RFs can be generated in patients with Sjögren’s syndrome and may play an important role in the pathogenesis of this autoimmune disease.

  3. Urofacial syndrome

    Directory of Open Access Journals (Sweden)

    Kamal F Akl

    2012-01-01

    Full Text Available The urofacial syndrome is characterized by functional obstructive uropathy asso-ciated with an inverted smile. The importance of the subject is that it sheds light, not only on the muscles of facial expression, but also on the inheritance of voiding disorders and lower urinary tract malformations. We report a 10-year-old-male patient who had the urofacial syndrome. Early diagnosis of the urofacial syndrome is important to avoid upper urinary tract damage and renal failure.

  4. Waardenburg syndrome.

    OpenAIRE

    Read, A P; Newton, V E

    1997-01-01

    Auditory-pigmentary syndromes are caused by physical absence of melanocytes from the skin, hair, eyes, or the stria vascularis of the cochlea. Dominantly inherited examples with patchy depigmentation are usually labelled Waardenburg syndrome (WS). Type I WS, characterised by dystopia canthorum, is caused by loss of function mutations in the PAX3 gene. Type III WS (Klein-Waardenburg syndrome, with abnormalities of the arms) is an extreme presentation of type I; some but not all patients are ho...

  5. Sweet Syndrome

    OpenAIRE

    Kasapçopur, Özgür; Sever, Lale; Çalışkan, Salim; Kodakoğlu, Ramazan; Mat, Cem; Kaner, Gültekin; Arısoy, Nil

    1996-01-01

    Sweet syndrome is a vasculitis characterized with fever leucocytosis neutrophilia and dermal neutrophilic infiltration In children Sweet syndrome usually occurs with secondary to infection and in adults to malignancy We report a Sweet syndrome in a five years old girl with respiratory infections otitis dactylitis long lasting fever and cutaneous rash A neutrophilic dermal infiltration is noted in cutaneous biopsy These signs have disappeared with corticosteroid treatment In conclusion Sweet s...

  6. Revesz syndrome

    Directory of Open Access Journals (Sweden)

    Dayane Cristine Issaho

    2015-04-01

    Full Text Available Revesz syndrome is a rare variant of dyskeratosis congenita and is characterized by bilateral exudative retinopathy, alterations in the anterior ocular segment, intrauterine growth retardation, fine sparse hair, reticulate skin pigmentation, bone marrow failure, cerebral calcification, cerebellar hypoplasia and psychomotor retardation. Few patients with this syndrome have been reported, and significant clinical variations exist among patients. This report describes the first Brazilian case of Revesz syndrome and its ocular and clinical features.

  7. Metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Gogia Atul

    2006-02-01

    Full Text Available The Metabolic syndrome is a widely prevalent and multi-factorial disorder. The syndrome has been given several names, including- the metabolic syndrome, the insulin resistance syndrome, the plurimetabolic syndrome, and the deadly quartet. With the formulation of NCEP/ATP III guidelines, some uniformity and standardization has occurred in the definition of metabolic syndrome and has been very useful for epidemiological purposes. The mechanisms underlying the metabolic syndrome are not fully known; however resistance to insulin stimulated glucose uptake seems to modify biochemical responses in a way that predisposes to metabolic risk factors. The clinical relevance of the metabolic syndrome is related to its role in the development of cardiovascular disease. Management of the metabolic syndrome involves patient-education and intervention at various levels. Weight reduction is one of the main stays of treatment. In this article we comprehensively discuss this syndrome- the epidemiology, pathogenesis, clinical relevance and management. The need to do a comprehensive review of this particular syndrome has arisen in view of the ever increasing incidence of this entitiy. Soon, metabolic syndrome will overtake cigarette smoking as the number one risk factor for heart disease among the US population. Hardly any issue of any primary care medical journal can be opened without encountering an article on type 2 diabetes, dyslipidemia or hypertension. It is rare to see type 2 diabetes, dyslipidemia, obesity or hypertension in isolation. Insulin resistance and resulting hyperinsulinemia have been implicated in the development of glucose intolerance (and progression to type 2 diabetes, hypertriglyceridemia, hypertension, polycystic ovary yndrome, hypercoagulability and vascular inflammation, as well as the eventual development of atherosclerotic cardiovascular disease manifested as myocardial infarction, stroke and myriad end organ diseases. Conversely

  8. Brugada syndrome

    Directory of Open Access Journals (Sweden)

    Bockeria O.L.

    2015-03-01

    Full Text Available Brugada syndrome is characterized by sudden death associated with one of several ECG patterns including incomplete right bundle-branch block and ST-segment elevation in the anterior precordial leads. According to the ECG patterns there are three types of Brugada syndrome. Brugada syndrome is genetically determined and has an autosomal dominant pattern of transmission in about 50% of familial cases. Nowadays implantation of cardioverter-defibrillator is the only proven method of sudden cardiac death prevention.

  9. Velocardiofacial syndrome.

    OpenAIRE

    Pike, A. C.; Super, M.

    1997-01-01

    Velocardiofacial syndrome is a syndrome of multiple anomalies that include cleft palate, cardiac defects, learning difficulties, speech disorder and characteristic facial features. It has an estimated incidence of 1 in 5000. The majority of cases have a microdeletion of chromosome 22q11.2. The phenotype of this condition shows considerable variation, not all the principal features are present in each case. Identification of the syndrome can be difficult as many of the anomalies are minor and ...

  10. Skin symptoms in four ectodermal dysplasia syndromes including two case reports of Rapp-Hodgkin-Syndrome.

    Science.gov (United States)

    Knaudt, Björn; Volz, Thomas; Krug, Markus; Burgdorf, Walter; Röcken, Martin; Berneburg, Mark

    2012-01-01

    The skin, hair and nail changes in four distinct ectodermal dysplasia syndromes are compared and reviewed. These syndromes comprise Christ-Siemens-Touraine syndrome; ectrodactyly, ectodermal dysplasia and cleft lip/palate syndrome; ankyloblepharon-ectodermal defects-cleft lip/palate syndrome and Rapp-Hodgkin syndrome. A comprehensive overview of the dermatological signs and symptoms in these syndromes was generated from the database of the Ectodermal Dysplasia Network Germany, the clinical findings in the patients seen in our department and an extensive review of the literature. The findings included abnormalities of skin, sweating, hair and nails. These clinical findings are discussed in relation to the underlying molecular defects known to play a role in these four ectodermal dysplasia syndromes. PMID:22759387

  11. Sheehan syndrome

    Science.gov (United States)

    Postpartum hypopituitarism; Postpartum pituitary insufficiency; Hypopituitarism Syndrome ... Malee MP. Pituitary and adrenal disorders in pregnancy. In: Gabbe ... Problem Pregnancies . 6th ed. Philadelphia, PA: Elsevier Mosby; ...

  12. What Is Down Syndrome?

    Science.gov (United States)

    ... NDSS Home » Down Syndrome » What Is Down Syndrome? What Is Down Syndrome? In every cell in the ... chromosome 21 causes the characteristics of Down syndrome. What Causes Down Syndrome? Regardless of the type of ...

  13. Marfan Syndrome (For Teens)

    Science.gov (United States)

    ... How Can I Help a Friend Who Cuts? Marfan Syndrome KidsHealth > For Teens > Marfan Syndrome Print A ... a genetic disorder called Marfan syndrome. What Is Marfan Syndrome? Marfan syndrome is named after Antoine Marfan, ...

  14. Down Syndrome: Eye Problems

    Science.gov (United States)

    ... En Español Read in Chinese What causes Down syndrome? Down syndrome is caused by a duplication of all ... in persons with Down syndrome. How common is Down syndrome? The frequency of Down syndrome is approximately 1 ...

  15. Proteus Syndrome Foundation

    Science.gov (United States)

    ... Gift Stock Gift Sunshine Society Contact Privacy Policy Proteus Syndrome Foundation The Proteus Syndrome Foundation , a 501c3 ... 1 Trial with ARQ 092 in Proteus Syndrome Proteus Syndrome Patient Registry The Proteus Syndrome Foundation Contact ...

  16. What's Right with My Mouse Model? New Insights into the Molecular and Cellular Basis of Cognition from Mouse Models of Rubinstein-Taybi Syndrome

    Science.gov (United States)

    Josselyn, Sheena A.

    2005-01-01

    The first gene-targeting studies that examined learning and memory in mice were performed in 1992 (Grant et al. 1992; Silva et al. 1992). The ultimate goal of this new field was to understand the molecular and cellular process underlying normal cognition and how they may be altered in disease states. In the years since these pioneering studies,…

  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. Molecular cloning and recombinant expression of the VP28 carboxyl-terminal hydrophilic region from a brazilian white spot syndrome virus isolate

    Directory of Open Access Journals (Sweden)

    Patricia Braunig

    2011-04-01

    Full Text Available In the present study, a fragment of the VP28 coding sequence from a Brazilian WSSV isolate (BrVP28 was cloned, sequenced and expressed in E. coli BL21(DE3 pLysS strain in order to produce the VP28 carboxyl-terminal hydrophilic region. The expression resulted in a protein of about 21 kDa, which was purified under denaturing conditions, resulting in a final highly purified BrVP28 preparation. The recombinant protein obtained can be used in several biotechnology applications, such as the production of monoclonal antibodies which could be used in the development of diagnostic tools as well as in the studies on the characterization of white spot syndrome virus (WSSV isolated in Brazil.

  19. Structural modeling of HLA-B*1502/peptide/carbamazepine/T-cell receptor complex architecture: implication for the molecular mechanism of carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis.

    Science.gov (United States)

    Zhou, Peng; Zhang, Shilei; Wang, Yewang; Yang, Chao; Huang, Jian

    2016-08-01

    Drug-induced adverse reactions are a significant problem in healthcare worldwide and are estimated to cost billions of dollars annually in the United States. A portion of such reactions is observed to strongly associate with certain human leukocyte antigen (HLA) alleles; one of the strongest associations is the HLA-B*1502 protein with carbamazepine (CBZ)-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) - the odds ratio value can even be higher than one thousand. The particularly strong association in CBZ-induced SJS/TEN suggests that the HLA-B*1502 is not only a genetic marker but also a participant in the pathogenesis of the disease. In the current study, we attempt to computationally model the atomic-level structure of the complete HLA-B*1502/peptide/CBZ/T-cell receptor (TCR) complex architecture based on prior knowledge obtained from epidemiological investigations as well as in vitro and in vivo assays. The model tells a different story about the molecular mechanism of CBZ-induced SJS/TEN from that previously reported for abacavir (ABC)-induced hypersensitivity (HSR); the CBZ molecule is located at the interface between HLA-B*1502/peptide and TCR, directly contacts the P3-P6 residues of antigen peptide, and bound within a pocket region encompassed by two TCR CDR3 fingers. Molecular dynamics simulation and binding energy analysis further reveal that the CBZ shows considerably high affinity to TCR over HLA-B*1502/peptide, which can tightly interact with the former rather than the latter. From the model, two hypotheses are proposed that can well explain most previous observations and are expected to guide next wet-lab experiments. This study could help to promote our understanding of the molecular mechanism and pathological implication underlying CBZ-induced SJS/TEN. PMID:26488421

  20. Transcriptional changes in response to X chromosome dosage in the mouse: implications for X inactivation and the molecular basis of Turner Syndrome

    Directory of Open Access Journals (Sweden)

    Sargent Carole A

    2010-02-01

    Full Text Available Abstract Background X monosomic mice (39,XO have a remarkably mild phenotype when compared to women with Turner syndrome (45,XO. The generally accepted hypothesis to explain this discrepancy is that the number of genes on the mouse X chromosome which escape X inactivation, and thus are expressed at higher levels in females, is very small. However this hypothesis has never been tested and only a small number of genes have been assayed for their X-inactivation status in the mouse. We performed a global expression analysis in four somatic tissues (brain, liver, kidney and muscle of adult 40,XX and 39,XO mice using the Illumina Mouse WG-6 v1_1 Expression BeadChip and an extensive validation by quantitative real time PCR, in order to identify which genes are expressed from both X chromosomes. Results We identified several genes on the X chromosome which are overexpressed in XX females, including those previously reported as escaping X inactivation, as well as new candidates. However, the results obtained by microarray and qPCR were not fully concordant, illustrating the difficulty in ascertaining modest fold changes, such as those expected for genes escaping X inactivation. Remarkably, considerable variation was observed between tissues, suggesting that inactivation patterns may be tissue-dependent. Our analysis also exposed several autosomal genes involved in mitochondrial metabolism and in protein translation which are differentially expressed between XX and XO mice, revealing secondary transcriptional changes to the alteration in X chromosome dosage. Conclusions Our results support the prediction that the mouse inactive X chromosome is largely silent, while providing a list of the genes potentially escaping X inactivation in rodents. Although the lower expression of X-linked genes in XO mice may not be relevant in the particular tissues/systems which are affected in human X chromosome monosomy, genes deregulated in XO mice are good candidates for

  1. Turner Syndrome

    Directory of Open Access Journals (Sweden)

    Ravinder K. Gupta, Ritu Gupta, Sunil Dutt Sharma

    2006-10-01

    Full Text Available Turner Syndrome is one of the important chromosomal disorders characterised by loss (total or part ofsex chromosome. The manifestations being peripheral edema, short stature, extra skin fold, webbing ofneck, renal and cardiovascular anomalies, sexual infantilism, learning disability etc. We present here aone month female baby who had classical features of Turner Syndrome. The karyotape analysis wasconsistent with the diagnosis.

  2. Turner Syndrome

    Directory of Open Access Journals (Sweden)

    Akcan AB.

    2013-06-01

    Full Text Available Turner syndrome is an important cause of short stature in girls and primer amenorrhea in young women that is usually caused by loss of part or all of an X chromosome. This topic will review the clinical manifestations, diagnosis and management of Turner syndrome.

  3. Tourette Syndrome.

    Science.gov (United States)

    Look, Kathy

    Tourette Syndrome has a history of being misdiagnosed or undiagnosed due to its unusual and complex symptoms. This paper describes: the symptoms of Tourette Syndrome; its etiology; age of onset; therapeutic methods, such as drug therapy, psychotherapy, diet control, and hypnosis; educational implications; and employment prospects. Several…

  4. Antiphospholipid syndrome

    DEFF Research Database (Denmark)

    Cervera, Ricard; Piette, Jean-Charles; Font, Josep;

    2002-01-01

    To analyze the clinical and immunologic manifestations of antiphospholipid syndrome (APS) in a large cohort of patients and to define patterns of disease expression.......To analyze the clinical and immunologic manifestations of antiphospholipid syndrome (APS) in a large cohort of patients and to define patterns of disease expression....

  5. Proteus syndrome

    Directory of Open Access Journals (Sweden)

    George Renu

    1993-01-01

    Full Text Available A case of proteus syndrome in a 20 year old male is repoted. Hemihypertrophy, asymmetric megalodactyly, linear epidermal naevus, naevus flammeus, angiokeratoma, lymphangioma circumscriptum, thickening of the palms and soles, scoliosis and varicose veins were present. There are only few reports of these cases in adults. The syndrome has not been reported from India.

  6. Burnout Syndrome

    OpenAIRE

    Panova, Gordana; Panov, Nenad; Stojanov, H; Sumanov, Gorgi; Panova, Blagica; Stojanovski, Angel; Nikolovska, Lence; Jovevska, Svetlana; Trajanovski, D; Asanova, D

    2013-01-01

    Introduction: Increasing work responsibilities, allocation of duties, loss of energy and motivation in everyday activities, emotional exhaustion, lack of time for themselves, insuffi cient time for rest and recreation, dissatisfaction in private life. All these symptoms can be cause of Burnout Syndrome. Aim: To see the importance of this syndrome, the consequences of job dissatisfaction, the environment, family and expression in drastic chan...

  7. Poland syndrome

    Directory of Open Access Journals (Sweden)

    Chandra Madhur Sharma

    2014-01-01

    Full Text Available Poland′s syndrome is a rare congenital condition, characterized by the absence of the sternal or breastbone portion of the pectoralis major muscle, which may be associated with the absence of nearby musculoskeletal structures. We hereby report an 8-year-old boy with typical features of Poland syndrome, the first documented case from Uttar Pradesh, India.

  8. Noonan Syndrome

    Directory of Open Access Journals (Sweden)

    Sanjeev K. Digra, Deep Aman Singh, Vikram Gupta, Ghanshyam Saini

    2004-10-01

    Full Text Available We report a 11 year old boy and his father both Noonan’s. Noonan syndrome occurs in 1 out of 2000live births. Short stature, webbing of neck, pectus carinatum or pectus excavatum, hypertelorismcubitus valgus, epicanthus, downward slanted palpebral fissures, ptosis, microganthia and earabnormalities are the common features of Noonan syndrome.

  9. Bloom's Syndrome

    Science.gov (United States)

    ... Niemann-Pick Disease, Type A Spinal Muscular Atrophy Tay-Sachs Disease Usher Syndrome, Type 1F and Type III ... Niemann-Pick Disease, Type A Spinal Muscular Atrophy Tay-Sachs Disease Usher Syndrome, Type 1F and Type III ...

  10. Complete amino acid sequence of the human alpha 5 (IV) collagen chain and identification of a single-base mutation in exon 23 converting glycine 521 in the collagenous domain to cysteine in an Alport syndrome patient

    DEFF Research Database (Denmark)

    Zhou, J; Hertz, Jens Michael; Leinonen, A; Tryggvason, K

    1992-01-01

    alleles. The mutation which was located to exon 23 was sequenced from a polymerase chain reaction-amplified product, and shown to be a G----T change in the coding strand. The mutation changed the GGT codon of glycine 521 to cysteine. The same mutation was found in one allele of the female cousin. The...

  11. Genetic Counseling and Testing for Common Hereditary Breast Cancer Syndromes: A Paper from the 2007 William Beaumont Hospital Symposium on Molecular Pathology

    OpenAIRE

    Allain, Dawn C.

    2008-01-01

    Throughout the past 15 years, the identification of several genes associated with hereditary breast cancer has fueled the growth of clinical genetic counseling and testing services. In addition, increased knowledge of the genetic and molecular pathways of the known hereditary breast cancer genes, as well as an increased understanding of the impact of testing on individuals has added to the ability to identify, manage, and provide psychosocial support for mutation carriers. This review provide...

  12. 2p15–p16.1 microdeletion syndrome: molecular characterization and association of the OTX1 and XPO1 genes with autism spectrum disorders

    OpenAIRE

    Liu, Xudong; Malenfant, Patrick; Reesor, Chelsea; Lee, Alana; Hudson, Melissa L; Harvard, Chansonette; Qiao, Ying; Persico, Antonio M.; Cohen, Ira L.; Chudley, Albert E.; Forster-Gibson, Cynthia; Rajcan-Separovic, Evica; Lewis, ME Suzanne; Holden, Jeanette JA

    2011-01-01

    Reports of unrelated individuals with autism spectrum disorder (ASD) and similar clinical features having overlapping de novo interstitial deletions at 2p15–p16.1 suggest that this region harbors a gene(s) important to the development of autism. We molecularly characterized two such deletions, selecting two genes in this region, exportin 1 (XPO1) and orthodenticle homolog 1 (OTX1) for association studies in three North American cohorts (Autism Spectrum Disorder – Canadian American Research Co...

  13. Guillain-Barré syndrome- and Miller Fisher syndrome-associated Campylobacter jejuni lipopolysaccharides induce anti-GM1 and anti-GQ1b Antibodies in rabbits.

    NARCIS (Netherlands)

    M.A. de Klerk; H.P. Endtz (Hubert); B.C. Jacobs (Bart); J.D. Laman (Jon); F.G.A. van der Meché; P.A. van Doorn (Pieter); C.W. Ang (Wim)

    2001-01-01

    textabstractCampylobacter jejuni infections are thought to induce antiganglioside antibodies in patients with Guillain-Barre syndrome (GBS) and Miller Fisher syndrome (MFS) by molecular mimicry between C. jejuni lipopolysaccharides (LPS) and gangliosides. We used purifi

  14. Sheldon-Hall syndrome

    Directory of Open Access Journals (Sweden)

    Bamshad Michael J

    2009-03-01

    Full Text Available Abstract Sheldon-Hall syndrome (SHS is a rare multiple congenital contracture syndrome characterized by contractures of the distal joints of the limbs, triangular face, downslanting palpebral fissures, small mouth, and high arched palate. Epidemiological data for the prevalence of SHS are not available, but less than 100 cases have been reported in the literature. Other common clinical features of SHS include prominent nasolabial folds, high arched palate, attached earlobes, mild cervical webbing, short stature, severe camptodactyly, ulnar deviation, and vertical talus and/or talipes equinovarus. Typically, the contractures are most severe at birth and non-progressive. SHS is inherited in an autosomal dominant pattern but about half the cases are sporadic. Mutations in either MYH3, TNNI2, or TNNT3 have been found in about 50% of cases. These genes encode proteins of the contractile apparatus of fast twitch skeletal muscle fibers. The diagnosis of SHS is based on clinical criteria. Mutation analysis is useful to distinguish SHS from arthrogryposis syndromes with similar features (e.g. distal arthrogryposis 1 and Freeman-Sheldon syndrome. Prenatal diagnosis by ultrasonography is feasible at 18–24 weeks of gestation. If the family history is positive and the mutation is known in the family, prenatal molecular genetic diagnosis is possible. There is no specific therapy for SHS. However, patients benefit from early intervention with occupational and physical therapy, serial casting, and/or surgery. Life expectancy and cognitive abilities are normal.

  15. Brugada Syndrome-An Update.

    Directory of Open Access Journals (Sweden)

    Oruganti Sai Satish

    2005-02-01

    Full Text Available A diagnostic triad characterizes Brugada syndrome. It consists of a right bundle branchblock, ST-segment elevation in leads V1-V3 and sudden cardiac death (SCD.Approximately 50% of patients with Brugada syndrome noted to have familial occurrence,this suggests a genetic component of the disease. Mutations in gene SCN5A, an encoder forhuman cardiac sodium channel on chromosome 3p21, causes Brugada syndrome. Beforeconsidering the diagnosis of Brugada syndrome, exclude precordial ST-segment elevationsecondary to acute coronary syndrome, electrolyte imbalance, myocarditis, drug over dosage(cocaine, tricyclic antidepressants, and arrhythmogenic right ventricularcardiomyopathy/dysplasia. Intravenous administration of ajmaline, flecainide, and procainamidemay exaggerate the ST-segment elevation, or unmask it when it is initially absentin patients with suspected Brugada syndrome. Programmed electrical stimulation (PES mayhelp in risk stratification, and in some cases, establish the diagnosis. However, the accuracyof PES in predicting outcome is debatable, especially in patients showing an asymptomaticBrugada ECG, and reporting no family history of SCD. Treatment with an implantable cardioverter-defibrillator (ICD is the only established effective therapy for the disease. WithICD therapy, the mortality rate at a 10 year follow-up was 0%. Supporting data for longtermpharmacological therapy with quinidine, or isoproterenol for prevention of SCD, inthese patients, is uncomplete. Future advances in understanding the molecular mechanismsof Brugada syndrome may provide answers to many of the controversial issues in the managementof this disease.

  16. Identification of a Novel De Novo Variant in the PAX3 Gene in Waardenburg Syndrome by Diagnostic Exome Sequencing: The First Molecular Diagnosis in Korea.

    Science.gov (United States)

    Jang, Mi-Ae; Lee, Taeheon; Lee, Junnam; Cho, Eun-Hae; Ki, Chang-Seok

    2015-05-01

    Waardenburg syndrome (WS) is a clinically and genetically heterogeneous hereditary auditory pigmentary disorder characterized by congenital sensorineural hearing loss and iris discoloration. Many genes have been linked to WS, including PAX3, MITF, SNAI2, EDNRB, EDN3, and SOX10, and many additional genes have been associated with disorders with phenotypic overlap with WS. To screen all possible genes associated with WS and congenital deafness simultaneously, we performed diagnostic exome sequencing (DES) in a male patient with clinical features consistent with WS. Using DES, we identified a novel missense variant (c.220C>G; p.Arg74Gly) in exon 2 of the PAX3 gene in the patient. Further analysis by Sanger sequencing of the patient and his parents revealed a de novo occurrence of the variant. Our findings show that DES can be a useful tool for the identification of pathogenic gene variants in WS patients and for differentiation between WS and similar disorders. To the best of our knowledge, this is the first report of genetically confirmed WS in Korea. PMID:25932447

  17. The Research Advance of Molecular Genetics of Marfan Syndrome%Marfan综合征分子遗传学研究新进展

    Institute of Scientific and Technical Information of China (English)

    陈喜军; 伍严安

    2006-01-01

    Marfan综合征(Marfan syndrome,MFS)是一种常染色体显性遗传性结缔组织病,其病变的微纤维主要牵累3个组织器官系统:骨骼、眼和心血管.1991年,研究发现FBN1突变能导致MFS;2004年,转化生长因子-β受体2(TGFBR2)被认定为MFSⅡ基因;2005年,研究报道TGFBR2突变或TGFBR1突变能够导致一种新的动脉瘤综合征.研究表明,在细胞外基质中,原纤维蛋白-1(fibilllin-1)与转化生长因子β(TGF-β)信号有功能上的相关性.MFS的病理机制可能与TGF-β信号异常有关.

  18. Hantavirus Pulmonary Syndrome, French Guiana

    OpenAIRE

    Matheus, Séverine; Djossou, Félix; Moua, David; Bourbigot, Anne Marie; Hommel, Didier; Lacoste, Vincent; Dussart, Philippe; Lavergne, Anne

    2010-01-01

    A systematic serological survey of patients suffering from symptoms suggestive of Hantavirus pulmonary syndrome allowed us to identify a native case in French Guiana. Partial molecular characterization of the implicated hantavirus revealed its close relationship with the Bolivian Rio Mamore virus. We tentatively named it Maripa virus.

  19. Kounis syndrome.

    Science.gov (United States)

    Ntuli, P M; Makambwa, E

    2015-10-01

    Kounis syndrome is characterised by a group of symptoms that manifest as unstable vasospastic or non-vasospastic angina secondary to a hypersensitivity reaction. It was first described by Kounis and Zavras in 1991 as the concurrence of an allergic response with an anaphylactoid or anaphylactic reaction and coronary artery spasm or even myocardial infarction. Since then, this condition has evolved to include a number of mast cell activation disorders associated with acute coronary syndrome. There are many triggering factors, including reactions to multiple medications, exposure to radiological contrast media, poison ivy, bee stings, shellfish and coronary stents. In addition to coronary arterial involvement, Kounis syndrome comprises other arterial systems with similar physiologies, such as mesenteric and cerebral circulation resulting in ischaemia/infarction of the vital organs. The incidence of this condition is difficult to establish owing to the number of potential instigating factors and its relatively infrequent documentation in the literature.We report the case of an HIV-negative 39-year-old man with no coronary risk factors or family history of premature coronary artery disease, who developed Kounis syndrome after the administration of fluoroquinolone for dysuria. However, to the best of our knowledge,no data on the incidence and prevalence of Kounis syndrome in South Africa have ever been reported in the literature. The recent understanding of Kounis syndrome has led to the condition being classified into three syndrome variants. PMID:26636160

  20. HYDROLETHALUS SYNDROME

    Directory of Open Access Journals (Sweden)

    Aradhana

    2013-06-01

    Full Text Available INTRODUCTION: Hydrolethalus Syndrome (HLS is a rare lethal genetic syndrome, recognized as a consequence of a study on Meckle syndrome in Finland .1 HLS is characterized by multiple developmental defects of fetus which include fetal hydrocephalus, agenesis of corpus callosum, absent midline structures of brain, Cleft lip and cleft palate, defective lobulation of lungs, micrognathia and very characteristic abnormality of polydactyly. About 80% of patients have polydactyly, in hands it is postaxial and preaxial in feet with duplicated big toe. A highly characteristic hallux duplex is seen in almost no other situation .2 Club feet is also common.

  1. Neuroacanthocytosis Syndromes

    Directory of Open Access Journals (Sweden)

    Walker Ruth H

    2011-10-01

    Full Text Available Abstract Neuroacanthocytosis (NA syndromes are a group of genetically defined diseases characterized by the association of red blood cell acanthocytosis and progressive degeneration of the basal ganglia. NA syndromes are exceptionally rare with an estimated prevalence of less than 1 to 5 per 1'000'000 inhabitants for each disorder. The core NA syndromes include autosomal recessive chorea-acanthocytosis and X-linked McLeod syndrome which have a Huntington´s disease-like phenotype consisting of a choreatic movement disorder, psychiatric manifestations and cognitive decline, and additional multi-system features including myopathy and axonal neuropathy. In addition, cardiomyopathy may occur in McLeod syndrome. Acanthocytes are also found in a proportion of patients with autosomal dominant Huntington's disease-like 2, autosomal recessive pantothenate kinase-associated neurodegeneration and several inherited disorders of lipoprotein metabolism, namely abetalipoproteinemia (Bassen-Kornzweig syndrome and hypobetalipoproteinemia leading to vitamin E malabsorption. The latter disorders are characterized by a peripheral neuropathy and sensory ataxia due to dorsal column degeneration, but movement disorders and cognitive impairment are not present. NA syndromes are caused by disease-specific genetic mutations. The mechanism by which these mutations cause neurodegeneration is not known. The association of the acanthocytic membrane abnormality with selective degeneration of the basal ganglia, however, suggests a common pathogenetic pathway. Laboratory tests include blood smears to detect acanthocytosis and determination of serum creatine kinase. Cerebral magnetic resonance imaging may demonstrate striatal atrophy. Kell and Kx blood group antigens are reduced or absent in McLeod syndrome. Western blot for chorein demonstrates absence of this protein in red blood cells of chorea-acanthocytosis patients. Specific genetic testing is possible in all NA syndromes

  2. Molecular cloning and characterizations of porcine SAMHD1 and its roles in replication of highly pathogenic porcine reproductive and respiratory syndrome virus.

    Science.gov (United States)

    Yang, Shen; Shan, Tongling; Zhou, Yanjun; Jiang, Yifeng; Tong, Wu; Liu, Fei; Wen, Feng; Zhang, Qingzhan; Tong, Guangzhi

    2014-12-01

    The sterile alpha motif and HD domain 1 (SAMHD1) protein is a novel innate immunity restriction factor that inhibits HIV-1 infection in myeloid cells. Here, we cloned the full-length SAMHD1 complementary DNA (cDNA) from porcine peripheral blood lymphocytes. The porcine SAMHD1 cDNA was of 3951 bp with an open reading frame of 1884 bp, encoding a polypeptide of 627 amino acids. Porcine SAMHD1 mRNA was detected in all swine tissues examined, with the higher expression in the tonsil, lung, liver, and lymph node tissues. The SAMHD1 protein was localized to the nucleus. Overexpression of SAMHD1 blocked the proliferation of HuN4, a highly pathogenic strain of porcine reproductive and respiratory syndrome virus (HP-PRRSV), in MARC-145 cells, by inhibiting the synthesis of the HuN4 complement RNA. The antiviral effects of the simian SAMHD1 protein were nearly equivalent to those of porcine SAMHD1 in the HuN4-infected MARC-145 cells. Phosphorylation analysis of SAMHD1 showed that overexpressed SAMHD1 protein was in primarily an unphosphorylated state. SAMHD1 overexpression increased the transcript abundance of IFN-stimulated genes ISG15 and ISG56. The mRNA levels of SAMHD1 and ISGs were significantly increased in porcine alveolar macrophages infected with HP-PRRSV. SAMHD1 protein level was also elevated, and the protein was not phosphorylated during infection. Collectively, our data indicate that SAMHDI inhibits HP-PRRSV proliferation through inhibiting the replication of HP-PRRSV. SAMHD1 might be the protein participating in the IFN signaling and is thus an important immunoregulatory protein in innate immunity. PMID:25106914

  3. Johanson-Blizzard syndrome.

    Science.gov (United States)

    Almashraki, Nabeel; Abdulnabee, Mukarram Zainuddin; Sukalo, Maja; Alrajoudi, Abdullah; Sharafadeen, Iman; Zenker, Martin

    2011-10-01

    Johanson-Blizzard syndrome (JBS) is a rare autosomal recessive disease characterized by exocrine pancreatic insufficiency, hypoplastic or aplastic nasal alae, cutis aplasia on the scalp, and other features including developmental delay, failure to thrive, hearing loss, mental retardation, hypothyroidism, dental abnormalities, and anomalies in cardiac and genitourinary systems. More than 60 cases of this syndrome have been reported to date. We describe the case of a male infant with typical symptoms of JBS. In addition, a new clinical feature which has not previously been documented, that is anemia requiring frequent blood transfusions and mild to moderate thrombocytopenia was observed. A molecular study was performed which revealed a novel homozygous UBR1 mutation. Possible explanations for this new association are discussed. PMID:22072859

  4. Schnitzler syndrome: clinical features and histopathology

    Directory of Open Access Journals (Sweden)

    Dingli D

    2015-06-01

    Full Text Available David Dingli,1,2 Michael J Camilleri3 1Division of Hematology, Department of Internal Medicine, 2Department of Molecular Medicine, 3Department of Dermatology, Mayo Clinic, Rochester, MN, USA Abstract: Schnitzler syndrome is a rare and underrecognized syndrome characterized by chronic urticaria, a monoclonal protein, and a variety of other symptoms, including fever, bone pain, organomegaly, and evidence of an acute phase response. Biopsy of an involved area of the skin shows a neutrophilic infiltrate without evidence of vasculitis or hemorrhage. Although the etiology of the syndrome is unknown, current evidence suggests this is an autoinflammatory syndrome. Recognition of this syndrome is critical since it is highly responsive to anakinra. Keywords: neutrophilic urticarial dermatosis, autoinflammatory syndrome, monoclonal gammopathy, neutrophilic dermatosis, anakinra 

  5. Piriformis syndrome

    Science.gov (United States)

    ... Wallet sciatica; Hip socket neuropathy; Pelvic outlet syndrome; Low back pain - piriformis ... medical help immediately if: You have sudden severe pain in your lower back or legs, along with muscle weakness or numbness ...

  6. Rett syndrome

    Science.gov (United States)

    An infant with Rett syndrome usually has normal development for the first 6 to 18 months. Symptoms range from ... of social engagement Ongoing, severe constipation and gastroesophageal reflux (GERD ) Poor circulation that can lead to cold ...

  7. Gardner Syndrome

    Science.gov (United States)

    ... syndromes. For more information, talk with an assisted reproduction specialist at a fertility clinic. How common is ... detected X-ray or computed tomography (CT or CAT) scan of the small bowel if adenomas are ...

  8. Piriformis Syndrome

    Science.gov (United States)

    ... syndrome occurs when this muscle presses on your sciatic nerve (the nerve that goes from your spinal cord ... cause the piriformis muscle to press against the sciatic nerve, such as sitting, walking up stairs or running. ...

  9. Marfan Syndrome

    Science.gov (United States)

    ... caved-in look. He also wore glasses for myopia (say: my-OH-pee-uh), or nearsightedness, which ... syndrome, this "glue" is weaker than normal. This causes changes in many systems of the body, but ...

  10. Aase syndrome

    Science.gov (United States)

    ... a provider who has experience treating anemias. A bone marrow transplant may be necessary if other treatment fails. ... counseling is recommended if you have a family history of this syndrome and wish to become pregnant.

  11. Hunter syndrome

    Science.gov (United States)

    ... to your health care provider for more information. Bone marrow transplant has been tried for the early-onset form, ... to have children and who have a family history of Hunter syndrome. Prenatal testing is available. Carrier ...

  12. Hurler syndrome

    Science.gov (United States)

    ... to your health care provider for more information. Bone marrow transplant has been used in several people with this ... Call your provider if: You have a family history of Hurler syndrome and are considering having children ...

  13. [Heptopulmonary syndrome].

    Science.gov (United States)

    Cuadrado, Antonio; Díaz, Ainhoa; Iruzubieta, Paula; Salcines, José Ramón; Crespo, Javier

    2015-01-01

    Hepatopulmonary syndrome is characterized by the presence of liver disease, pulmonary vascular dilatations, and arterial hypoxemia. It is usually associated with cirrhosis of any origin, but has been described in other liver diseases, both acute and chronic, and not always associated with portal hypertension. The gold standard method to detect pulmonary vascular dilations is contrast enhancement echocardiography with saline and is essential for the diagnosis of hepatopulmonary syndrome. These dilatations reflect changes in the pulmonary microvasculature (vasodilatation, intravascular monocyte accumulation, and angiogenesis) and induce a ventilation/perfusion mismatch, or even true intrapulmonary shunts, which eventually trigger hypoxemia. This syndrome worsens patients' prognosis and impairs their quality of life and may lead to the need for liver transplantation, which is the only effective and definitive treatment. In this article, we review the etiological, pathophysiological, clinical and therapeutic features of this syndrome. PMID:25840463

  14. Turcot Syndrome

    Science.gov (United States)

    ... procedure done in conjunction with in-vitro fertilization (IVF). It allows people who carry a specific known ... screening? If you are concerned about your family history and think your family may have Turcot syndrome, ...

  15. Levator Syndrome

    Science.gov (United States)

    ... 2 Diabetes, Heart Disease a Dangerous Combo Are 'Workaholics' Prone to OCD, Anxiety? ALL NEWS > Resources First ... are variations of levator syndrome. The muscle spasm causes pain that typically is not related to defecation. ...

  16. Pendred Syndrome

    Science.gov (United States)

    ... Health & Human Services National Institutes of Health Search Search form Search A–Z Index Español Menu Home ... children, the thyroid is important for normal growth and development. Children with Pendred syndrome, however, rarely have problems ...

  17. Goodpasture syndrome

    Science.gov (United States)

    ... glomerulonephritis with pulmonary hemorrhage; Pulmonary renal syndrome; Glomerulonephritis - pulmonary hemorrhage ... when urinating Nausea and vomiting Pale skin Swelling (edema) in any area of the body, especially in the legs

  18. Tourette Syndrome

    Science.gov (United States)

    ... methylphenidate and clonidine in children with ADHD and tics. Developing New Treatments for Tourette Syndrome: Clinical and Basic Science Dialogue Publicaciones en Español Síndrome de Tourette Prepared ...

  19. Barth Syndrome

    DEFF Research Database (Denmark)

    Saric, Ana; Andreau, Karine; Armand, Anne-Sophie;

    2016-01-01

    Mutations in the gene encoding the enzyme tafazzin, TAZ, cause Barth syndrome (BTHS). Individuals with this X-linked multisystem disorder present cardiomyopathy (CM) (often dilated), skeletal muscle weakness, neutropenia, growth retardation, and 3-methylglutaconic aciduria. Biopsies of the heart...

  20. [DIDMOAD syndrome].

    Science.gov (United States)

    Alicanoğlu, R; Canbakan, B; Yildiz, N; Arikan, E; Kundur, H; Bahtiyar, K; Sayali, E

    1994-01-01

    The DIDMOAD or so called Wolfram syndrome is a hereditary disease with autosomal-recessive transmission showing 4 main features: diabetes mellitus, diabetes insipidus, nervus opticus atrophia and deafness. Beside this it shows multiple organ involvement. Our 38-year old male patient, showing all above mentioned features except deafness had urinary tract involvement and neurological symptoms. EEG, cerebral MRI, tests with evoked potentials and HLA-typing were performed to discuss the aetiopathogenetic background in our patient. Almost all symptoms of the Wolfram syndrome can be mixed up with complications of diabetes mellitus, which is usually the first symptom of the Wolfram syndrome. Because of this, wrong diagnosis is not rare. Hence in differential diagnosis in any diabetes mellitus type I patient, the possibility of the Wolfram syndrome should be discussed. PMID:8023526

  1. Heyde's syndrome

    Directory of Open Access Journals (Sweden)

    Perišić Nenad

    2006-01-01

    Full Text Available Background: Heyde's syndrome implies an association of calcified aortic stenosis with the high gradient of pressure and angiodysplasic bleeding from the digestive tract. It has been proven that in patients with this syndrome, acquired form of von Willebrand type II A develops. Replacing of aortic valves by artificial ones brings about the spontaneous retreat of coagulation disorder, and the stoppage of the digestive tract bleeding. Case report. We reported two patients with the Heyde's syndrome. In one of the patients the aortic valves were replaced by biologic valves, after which the digestive tract bleeding stopped, while the second patient was treated conservatively due to a high operation risk. Conclusion. Patients with Heyde's syndrome are a complex multidisciplinary problem, thus their adequate treatment requires a team work in order to provide the most rational type of therapy for each patient separately.

  2. Reifenstein syndrome

    Science.gov (United States)

    ... male sex hormones (androgens). Testosterone is a male sex hormone. This disorder is a type of androgen insufficiency syndrome. ... Donohoue PA. Disorders of sex development. In: Kliegman RM, Stanton ... J, Schor N, Behrman RE, eds. Nelson Textbook of Pediatrics . ...

  3. HELLP syndrome

    Science.gov (United States)

    ... out of 1,000 pregnancies. In women with preeclampsia or eclampsia , the condition develops in 10 to ... have high blood pressure and are diagnosed with preeclampsia before they develop HELLP syndrome. In some cases, ...

  4. Kindler syndrome

    OpenAIRE

    Kaviarasan P; Prasad P; Shradda; Viswanathan P

    2005-01-01

    Kindler syndrome is a rare autosomal recessive disorder associated with skin fragility. It is characterized by blistering in infancy, photosensitivity and progressive poikiloderma. The syndrome involves the skin and mucous membrane with radiological changes. The genetic defect has been identified on the short arm of chromosome 20. This report describes an 18-year-old patient with classical features like blistering and photosensitivity in childhood and the subsequent development of poikiloderm...

  5. Turner Syndrome

    OpenAIRE

    Ramachandran Sudarshan; G Sree Vijayabala; KS Prem Kumar

    2012-01-01

    Turner syndrome is a genetic disorder that affects mostly females. Affected females have characteristic features such as short stature, premature ovarian failure, and several other features. Oral manifestations of this condition are not much discussed in the literature. But reported literature includes teeth, palate, periodontal and salivary changes. So the aim of this review is to illustrate the general manifestations, and especially the oral manifestations of Turner syndrome and evaluate th...

  6. Pendred's syndrome

    International Nuclear Information System (INIS)

    This report describes Pendred's syndrome in three siblings of a consanguineous marriage, belonging to Rahimyar Khan. The children presented with deafmutism and goiters. The investigations included scintigram, perchlorate discharge test and audiometery. The perchlorate discharge was positive in index case. Bilateral sensorineural hearing defect was detected on Pure Tone Average (PTA) audiometry. Meticulous clinical and laboratory evaluation is mandatory for the detection of rare disorders like Pendred's syndrome. (author)

  7. Turner Syndrome: Other FAQs

    Science.gov (United States)

    ... NICHD Research Information Clinical Trials Resources and Publications Turner Syndrome: Other FAQs Skip sharing on social media links ... been diagnosed with Turner syndrome. Now what? Is Turner syndrome inherited? Turner syndrome is usually not inherited, but ...

  8. Learning about Down Syndrome

    Science.gov (United States)

    ... for the genetic terms used on this page Learning About Down Syndrome What is Down syndrome? What ... Down syndrome? People who have Down syndrome have learning difficulties, mental retardation, a characteristic facial appearance, and ...

  9. Burning Mouth Syndrome

    Science.gov (United States)

    ... OralHealth > Topics > Burning Mouth Syndrome > Burning Mouth Syndrome Burning Mouth Syndrome Main Content Key Points Symptoms Diagnosis Primary and Secondary BMS Treatment Helpful Tips Key Points Burning mouth syndrome is burning pain in the mouth that may ...

  10. Homozygosity for Waardenburg syndrome.

    OpenAIRE

    Zlotogora, J; Lerer, I; Bar-David, S; Ergaz, Z; Abeliovich, D

    1995-01-01

    In a large kindred including many individuals affected with Waardenburg (WS) type 1 (WS1) syndrome, a child affected with a very severe form of WS type 3 was born. This child presented with dystopia canthorum, partial albinism, and very severe upper-limb defects. His parents were first cousins, both affected with a mild form of WS1. Molecular analysis of PAX3, the gene that was determined by linkage to cause the disorder in the family, demonstrated a novel missense mutation (S84F) in exon 2 o...

  11. Antiphospholipid syndrome.

    Science.gov (United States)

    Ruiz-Irastorza, Guillermo; Crowther, Mark; Branch, Ware; Khamashta, Munther A

    2010-10-30

    The antiphospholipid syndrome causes venous, arterial, and small-vessel thrombosis; pregnancy loss; and preterm delivery for patients with severe pre-eclampsia or placental insufficiency. Other clinical manifestations are cardiac valvular disease, renal thrombotic microangiopathy, thrombocytopenia, haemolytic anaemia, and cognitive impairment. Antiphospholipid antibodies promote activation of endothelial cells, monocytes, and platelets; and overproduction of tissue factor and thromboxane A2. Complement activation might have a central pathogenetic role. Of the different antiphospholipid antibodies, lupus anticoagulant is the strongest predictor of features related to antiphospholipid syndrome. Therapy of thrombosis is based on long-term oral anticoagulation and patients with arterial events should be treated aggressively. Primary thromboprophylaxis is recommended in patients with systemic lupus erythematosus and probably in purely obstetric antiphospholipid syndrome. Obstetric care is based on combined medical-obstetric high-risk management and treatment with aspirin and heparin. Hydroxychloroquine is a potential additional treatment for this syndrome. Possible future therapies for non-pregnant patients with antiphospholipid syndrome are statins, rituximab, and new anticoagulant drugs. PMID:20822807

  12. Clinical and Molecular Diagnosis in a Big Chinese Family with Pendred Syndrome%一个Pendred综合征家系的临床及SLC26A4基因检测分析

    Institute of Scientific and Technical Information of China (English)

    陶峥; 柴永川; 李磊; 李晓华; 杨涛; 吴皓

    2012-01-01

    Objective To elucidate the clinical diagnosis and molecular pathogenesis of Pendred syndrome in a big Chinese family. Methods Clinical materials and DNA sample were obtained from the Pendred syndrome family. The exons and the flanking splicing sites of SLC26A4 were screened in the 4 major patients in this family by nested PCR and direct sequencing. Results The clinical characterizations of patients in this family included the prelingual sensorineural hearing loss, dysphonia, goiter, normal thyroid function and enlarged vestibular aqueduct. A total of 4 different types of SLC26A4 mutations were identified in the family. The proband , his father, his mother and his sister were carried with different SLC26A4 biallelic mutations which were p. Q514P and p. H723R,p. N392Y and p. H723R,c. 1548insC and p. Q514P,p. N392Y and c. 1548insC, respectively. Conclusion The proband, his father, his mother and his sister with Pendred syndrome were caused by different biallelic mutations of SLC26A4. In the 4 types of SLC26A4 mutations, p. Q514P is novel, which has not been yet reported in the previous literatures.%目的 探讨Pendred综合征的临床表现及SLC26A4基因检测特点.方法 对一个多人患病的Pendred综合征家系进行详尽的临床表型分析,并对其中4例耳聋患者进行SLC26A4基因全编码序列及侧翼序列的检测.结果 该家系共三代15人,其中6人(40.0%)为耳聋患者,6例均为语前感音神经性聋,2例(Ⅰ-3和Ⅱ-7)表现为言语障碍,5例(Ⅱ-4、Ⅱ-5、Ⅱ-7、Ⅲ-1、Ⅲ-2)伴单纯甲状腺肿大、3例(Ⅱ-5、Ⅲ-1、Ⅲ-2)伴前庭水管扩大.Ⅱ-4、Ⅱ-5、Ⅲ-1和Ⅲ-2这4例耳聋患者中共发现SLC26A4基因四种不同的突变,患病成员中先证者(Ⅲ-1)及其父亲(Ⅱ-4)、母亲(Ⅱ-5)和妹妹(Ⅲ-2)分别具有p.Q514P和p.H723R、p.N392Y和p.H723R、c.1548insC和p.Q514P、p.N392Y和c.1548ins C双等位基因突变.结论 该家系先证者及其父母、妹妹分别由SLC26A4基因不同复合杂

  13. Serotonin Syndrome

    Directory of Open Access Journals (Sweden)

    Harold Muñoz Cortés

    2004-08-01

    Full Text Available The serotonin syndrome is a clinical condition associated with serotonin agonists, prescribed to treat some psychiatric and non psychiatric diseases like affective, anxiety and pain disorders. Is due to an excessive stimulation of central and peripheral serotonin receptors that leads to mental, autonomic and neuromuscular changes. Usually the disorder resolves within the first 24 hours after the medications are discontinued, however some patients progress to a multiple organ failure and die. This paper is a theoretical review of the fundamental aspects of the serotonin syndrome, beginning with a brief review of the anatomic and physiologic features of serotonin system, to continue to examine the most relevant historic, diagnosis, clinical and treatment aspects of the syndrome.

  14. Postconcussional Syndrome

    Directory of Open Access Journals (Sweden)

    Necla Keskin

    2013-02-01

    Full Text Available Postconcussional syndrome is characterized by somatic, cognitive and psychiatric (emotional, behavioral symptoms that occurs after mild traumatic brain injury. It has been known that these symptoms recover fully within 3-6 months almost in 90% of patients. Although its etiology is still controversial, biological, psychological and social factors may account for the development and continuation of the symptoms. Diagnosis is based on the subjective complaints. To find out an objective method for definite diagnosis, trials searching for both neuroimaging and specific serum biomarkers stil continue. The treatment of the syndrome is mainly of palliative nature. Information, education, reassurance and multifaceted rehabilitation programmes can be beneficial. There are promising trials reporting the effectiveness of cognitive behavioral therapy in the treatment of postconcussional syndrome. [Archives Medical Review Journal 2013; 22(1.000: 96-109

  15. Nutcracker syndrome

    International Nuclear Information System (INIS)

    Purpose: The purpose of this case study is to highlight the symptoms of the Nutcracker Syndrome (NCS), the methods of clinical investigations and the importance of differential diagnosis. Introduction: The NCS refers to left renal vein entrapment caused by abnormal branching patterns of the superior mesenteric artery from the aorta.1,2 Clinical case presentation: A 27 years old female presented to the emergency department with complaints of abdominal discomfort, bloating, loose bowel motions and irregular micro-haematuria. The radiologist's report indicated the findings from computed tomography examination to be consistent with anterior NCS. Discussion: In most of the NCS cases the clinical symptoms are non-specific.3 The syndrome is caused by a vascular disorder, but its clinical manifestation can relate to a wide range of abdominal, urological, endovascular or gynaecological pathologies.4 Conclusion: Nutcracker Syndrome is a relatively rare disease and underdiagnosed may lead to left renal vein thrombosis

  16. Refeeding syndrome

    Directory of Open Access Journals (Sweden)

    Tripathy Swagata

    2008-01-01

    Full Text Available We report a case of a fifty-year-old male who was admitted with a three month history of increasing weakness, prostration, decreasing appetite and inability to swallow. The patient was a chronic alcoholic, unemployed, and of very poor socioeconomic background. The patient was initially investigated for upper GI malignancy, Addisons disease, bulbar palsy and other endocrinopathies. Concurrent management was started for severe electrolyte abnormalities and enteral nutritional supplementation was begun. By the fourth day of feeding patient developed severe hypophosphatemia and other life-threatening features suggesting refeeding syndrome. The patient was managed for the manifestations of refeeding syndrome. A final diagnosis of chronic alcoholic malnutrition with refeeding syndrome was made. Refeeding of previously starving patients may lead to a variety of complications including sudden death.

  17. Eagle's Syndrome

    Directory of Open Access Journals (Sweden)

    Pinheiro, Thaís Gonçalves

    2014-01-01

    Full Text Available Introduction: Eagle's syndrome is characterized by cervicopharyngeal signs and symptoms associated with elongation of the styloid apophysis. This elongation may occur through ossification of the stylohyoid ligament, or through growth of the apophysis due to osteogenesis triggered by a factor such as trauma. Elongation of the styloid apophysis may give rise to intense facial pain, headache, dysphagia, otalgia, buzzing sensations, and trismus. Precise diagnosis of the syndrome is difficult, and it is generally confounded by other manifestations of cervicopharyngeal pain. Objective: To describe a case of Eagle's syndrome. Case Report: A 53-year-old man reported lateral pain in his neck that had been present for 30 years. Computed tomography (CT of the neck showed elongation and ossification of the styloid processes of the temporal bone, which was compatible with Eagle's syndrome. Surgery was performed for bilateral resection of the stylohyoid ligament by using a transoral and endoscopic access route. The patient continued to present pain laterally in the neck, predominantly on his left side. CT was performed again, which showed elongation of the styloid processes. The patient then underwent lateral cervicotomy with resection of the stylohyoid process, which partially resolved his painful condition. Final Comments: Patients with Eagle's syndrome generally have a history of chronic pain. Appropriate knowledge of this disease is necessary for adequate treatment to be provided. The importance of diagnosing this uncommon and often unsuspected disease should be emphasized, given that correct clinical-surgical treatment is frequently delayed. The diagnosis of Eagle's syndrome is clinical and radiographic, and the definitive treatment in cases of difficult-to-control pain is surgical.

  18. Ocular pseudoexfoliation syndrome

    Directory of Open Access Journals (Sweden)

    Đorđević-Jocić Jasmina

    2010-01-01

    Full Text Available Introduction. This study was aimed at providing an update on most recent developments regarding ocular and systemic manifestations and complications, clinical diagnosis and management, and molecular patophysiology of pseudoexfoliation syndrome. Method. Review of recent literature and own clinical and laboratory studies. Results. Pseudoexfoliation syndrome is an age-related disease in which abnormal fibrillar extracellular material is produced and accumulated in many ocular tissues. Recent progress and advances have led to improvements in clinical management by understanding the effects of the pseudoexfoliation process on the ocular tissues, by refining diagnostic criteria and applying new treatment regimes, and by developing preventive strategies to reduce surgical complications. Increasing evidence of systemic associations of cardiovascular, cerebrovascular, abdominal aorta aneurysm can provide better understanding and management of this condition, and new therapeutic goal. The current pathogenesis concept describes psuedoexfoliation syndrome as an elastic microfibrillopathy involving transforming growth factor-b, matrix metalloproteinase oxidative stress. Conclusion. Despite extensive research, the exact chemical composition of exfoliation material remains unknown. The presence of pseudoexfoliation should alert the physician to the increased risks of intraocular surgery, most commonly zonular dehiscence, capsular rupture, and vitreous loss during cataract extraction. Its associated clinical signs are important in the detection and management of glaucoma.

  19. Waardenburg syndrome

    Directory of Open Access Journals (Sweden)

    Tagra Sunita

    2006-01-01

    Full Text Available Waardenburg syndrome is a rare inherited and genetically heterogenous disorder of neural crest cell development. Four distinct subtypes showing marked interfamilial and intrafamilial variability have been described. We report a girl showing constellation of congenital hearing impairment with 110 dB and 105 dB loss in right and left ear respectively, hypoplastic blue iridis, white forelock, dystopia canthorum and broad nasal root. Other affected relatives of the family, with variable features of the syndrome, have been depicted in the pedigree.

  20. [Eisenmenger syndrome].

    Science.gov (United States)

    Jensen, Annette Schophuus; Iversen, Kasper; Vejlstrup, Niels G; Hansen, Peter Bo; Søndergaard, Lars

    2009-04-01

    Congenital heart disease with left-to-right shunt can induce proliferation, vasoconstriction and thrombosis in the pulmonary vascular bed. Eventually, the patient may develop Eisenmenger syndrome defined as pulmonary arterial hypertension caused by high pulmonary vascular resistance with right-to-left shunt and cyanosis. Patients with Eisenmenger syndrome suffer a high risk of complications in connection with acute medical conditions, extra-cardiac surgery and pregnancy. This article describes the precautions that should be taken to reduce morbidity and mortality in these patients. PMID:19416617

  1. Rapunzel syndrome

    International Nuclear Information System (INIS)

    An 18-year-old single female patient, presented with non specific gastrointestinal symptoms of anorexia, abdominal pain, and change in bowel habit. Clinically she was anemic, cachectic, and depressed. Abdominal examination revealed mobile epigastric mass. The scalp alopecia and endoscopy coupled by computed tomography scan, confirmed the diagnoses of trichobezoar, but it was not diagnosed as Rapunzel syndrome except after laparotomy, gastrotomy, and enterotomy. There are less than 16 cases of Rapunzel syndrome described worldwide, and this is the first case to be described in the middle east. (author)

  2. Joubert syndrome

    International Nuclear Information System (INIS)

    Joubert syndrome is a rare malformation of the posterior fossa, mainly affecting the cerebellar vermis, which generally appears as a dysplastic lesion. Other structures of the cervico medullary junction may be involved, with accompanying brainstem hypoplasia according to neuroimaging studies. The diagnosis is usually reached during, childhood, based on a constellation of changes in the child's neurological development that are supported by the results of imaging studied. Respiratory problems are the most common signs in newborns,leading to the suspicion of the presence of this syndrome. (Author) 11 refs

  3. Turner Syndrome

    Directory of Open Access Journals (Sweden)

    Ramachandran Sudarshan

    2012-08-01

    Full Text Available Turner syndrome is a genetic disorder that affects mostly females. Affected females have characteristic features such as short stature, premature ovarian failure, and several other features. Oral manifestations of this condition are not much discussed in the literature. But reported literature includes teeth, palate, periodontal and salivary changes. So the aim of this review is to illustrate the general manifestations, and especially the oral manifestations of Turner syndrome and evaluate their possible management. [Archives Medical Review Journal 2012; 21(4.000: 246-252

  4. Eisenmengers syndrom

    DEFF Research Database (Denmark)

    Jensen, Annette Schophuus; Iversen, Kasper; Vejlstrup, Niels G;

    2009-01-01

    Congenital heart disease with left-to-right shunt can induce proliferation, vasoconstriction and thrombosis in the pulmonary vascular bed. Eventually, the patient may develop Eisenmenger syndrome defined as pulmonary arterial hypertension caused by high pulmonary vascular resistance with right......-to-left shunt and cyanosis. Patients with Eisenmenger syndrome suffer a high risk of complications in connection with acute medical conditions, extra-cardiac surgery and pregnancy. This article describes the precautions that should be taken to reduce morbidity and mortality in these patients. Udgivelsesdato...

  5. Olmsted syndrome

    Directory of Open Access Journals (Sweden)

    Kumar Pramod

    2008-01-01

    Full Text Available Olmsted syndrome is a rare disorder characterized by the combination of periorificial, keratotic plaques and bilateral palmoplantar keratoderma. New associated features are being reported. Olmsted syndrome is particularly rare in a female patient, and we report such a case in a six year-old Indian girl, who presented with keratoderma of her soles since birth and on her palms since the age of two years along with perioral and perinasal hyperkeratosis. She had sparse, light brown, thin hair. Although the psychomotor development of the child was normal until 18 months of age, the keratoderma plaques had restricted the child′s mobility after that stage.

  6. Eagle syndrome

    International Nuclear Information System (INIS)

    Eagle syndrome occurs due to elongation of the styloid process or calcification of the stylohyoid ligament, which then may produce a pain sensation due the pressure exerted on various structures in the head and neck. When suspected, imaging helps in identifying the abnormally elongated styloid process or the calcified ligament. In recent years, three-dimensional CT (3DCT) has proved to be valuable in these cases. We report the case of a 62-year-old man with this syndrome in whom imaging with 3DCT conclusively established the diagnosis

  7. Lemierre's syndrome.

    LENUS (Irish Health Repository)

    O'Dwyer, D N

    2012-02-01

    Lemierre\\'s syndrome is a rare disease that results in an oropharyngeal infection, which precipitates an internal jugular vein thrombosis and metastatic infection. Fusobacterium necrophorum is an anaerobic Gram-negative bacillus and has been identified as the causative agent. We describe the case of a young girl whose presentation and diagnosis were confounded by a history of valvular heart disease. Infection of heart valves can produce many of the signs and symptoms associated with Lemierre\\'s syndrome. We describe the diagnosis, investigation and optimal management of this rare disorder.

  8. Morbihan syndrome

    Directory of Open Access Journals (Sweden)

    Stefano Veraldi

    2013-01-01

    Full Text Available We report a case of severe Morbihan syndrome (chronic erythematous edema of the upper portion of the face in a 60-year-old man. The syndrome was characterized clinically by erythematous edema involving the forehead, glabella, and both eyelids, because of which the patient was not able to open completely his eyes. Furthermore, erythema and telangiectasiae were visible on the nose and cheeks. Laboratory and instrumental examinations were within normal ranges or negative. Histopathological examination showed dermal edema, perivascular and periadnexal lympho-histiocytic infiltrate, and sebaceous gland hyperplasia. Oral isotretinoin was ineffective despite the relatively long duration of the therapy (26 weeks.

  9. Burnout syndrome

    OpenAIRE

    Bábská, Simona

    2014-01-01

    This bachelor thesis deals with the so-called burnout syndrome, which, as I believe, is getting to be a serious problem in today´s busy world. This issue deserves a full attention especially from those concerned – workers in assisting professions. What usually precedes the burnout syndrome is a big enthusiasm and motivation for work in which a potential patient can help other people and get them out of their troubles, sometimes he /she feels even like having a mission. However, without kno...

  10. Comparison of molecular and biological characteristics of a modified live porcine reproductive and respiratory syndrome virus (PRRSV) vaccine (ingelvac PRRS MLV), the parent strain of the vaccine (ATCC VR2332), ATCC VR2385, and two recent field isolates of PRRSV.

    Science.gov (United States)

    Opriessnig, T; Halbur, P G; Yoon, K-J; Pogranichniy, R M; Harmon, K M; Evans, R; Key, K F; Pallares, F J; Thomas, P; Meng, X J

    2002-12-01

    The objectives of this study were to compare the molecular and biological characteristics of recent porcine reproductive and respiratory syndrome virus (PRRSV) field isolates to those of a modified live virus (MLV) PRRS vaccine and its parent strain. One hundred seventeen, 4-week-old pigs were randomly assigned to six groups. Group 1 (n = 20) served as sham-inoculated negative controls, group 2 (n = 19) was inoculated with Ingelvac PRRS MLV vaccine, group 3 (n = 20) was inoculated with the parent strain of the vaccine (ATCC VR2332), group 4 (n = 19) was inoculated with vaccine-like PRRSV field isolate 98-38803, group 5 (n = 19) was inoculated with PRRSV field isolate 98-37120, and group 6 (n = 20) was inoculated with known high-virulence PRRSV isolate ATCC VR2385. The levels of severity of gross lung lesions (0 to 100%) among the groups were significantly different at both 10 (P < 0.0001) and 28 days postinoculation (p.i.) (P = 0.002). At 10 days p.i., VR2332 (26.5% +/- 4.64%) and VR2385 (36.4% +/- 6.51%) induced gross lesions of significantly greater severity than 98-38803 (0.0% +/- 0.0%), 98-37120 (0.8% +/- 0.42%), Ingelvac PRRS MLV (0.9% +/- 0.46%), and negative controls (2.3% +/- 1.26%). At 28 days p.i., 98-37120 (17.2% +/- 6.51%) induced gross lesions of significantly greater severity than any of the other viruses. Analyses of the microscopic-interstitial-pneumonia-lesion scores (0 to 6) revealed that VR2332 (2.9 +/- 0.23) and VR2385 (3.1 +/- 0.35) induced significantly more severe lesions at 10 days p.i. At 28 days p.i., VR2385 (2.5 +/- 0.27), VR2332 (2.3 +/- 0.21), 98-38803 (2.6 +/- 0.29), and 98-37120 (3.0 +/- 0.41) induced significantly more severe lesions than Ingelvac PRRS MLV (0.7 +/- 0.17) and controls (0.7 +/- 0.15). The molecular analyses and biological characterizations suggest that the vaccine-like isolate 98-38803 (99.5% amino acid homology based on the ORF5 gene) induces microscopic pneumonia lesions similar in type to, but different in severity

  11. Molecular etiology of non-syndromic hearing impairment in a Chinese family%非综合征性耳聋一家系分子病因学分析

    Institute of Scientific and Technical Information of China (English)

    孙勍; 单希征; 马丽涛; 康东洋; 张昕; 刘新; 王国建; 袁慧军; 韩东一

    2009-01-01

    Objective To investigate the molecular etiology of non-syndromic hearing impairment in two patients in a maternal inherited deafness Chinese family. Methods Peripheral blood specimens were collected and DNA templates extracted. The complete mitochondrial genomes and GJB2 geoe were sequenced in an ABI 3100 Avant sequencer. Results The proband(Ⅲ-5) and her elder sister(Ⅲ-1) were found to carry the mtDNA 12SrRNA C1494T mutation. The GJB2 gene showed no mutations. The proband had the history of using aminoglycosides before hearing loss, and exhibited severe sensorineural hearing impairment; the proband's sister had no history of using aminoglycosides, and showed moderate sensorineural hearing impairment. Conclusion The molecular etiology of each individual patient in a family yaries with individual genetic background.%目的 从分子病因学角度分析一具有母系遗传特性的非综合征性耳聋家系耳聋原因.方法 对该家系成员进行线粒体基因全序列及缝隙连接蛋白26编码基因(GJB2)全序列分析.结果 接受检测的该家系先证者(Ⅲ-5)及另一母系成员(Ⅲ-1)均携带线粒体DNA 12SrRNA C1494T突变;先证者聋前有氨基糖苷类抗生素应用史,表现为双侧重度感音神经性耳聋,携带线粒体DNA12SrRNA C1494T突变的另一母系成员(Ⅲ-1)聋前无氨基糖苷类抗生素应用史,表现为双侧中度感音神经性耳聋.GJB2基因检测未发现致病突变.结论 线粒体DNA 12SrRNA C1494T突变是氨基糖苷类抗生素致聋的原因之一,该突变致聋程度的不一致性可能与个体遗传背景不同有关.

  12. Marfan syndrome masked by Down syndrome?

    NARCIS (Netherlands)

    J.C. Vis; K. van Engelen; J. Timmermans; B.C. Hamel; B.J.M. Mulder

    2009-01-01

    Down syndrome is the most common chromosomal abnormality. A simultaneous occurrence with Marfan syndrome is extremely rare. We present a case of a 28-year-old female with Down syndrome and a mutation in the fibrillin-1 gene. The patient showed strikingly few manifestations of Marfan syndrome. Althou

  13. Metabolic Syndrome

    Science.gov (United States)

    ... If you already have metabolic syndrome, making these healthy lifestyle choices can help reduce your risk of heart disease and other health problems. If lifestyle changes alone can’t control your ... to help. Maintain a healthy weight Your doctor can measure your body mass ...

  14. Nephrotic Syndrome

    Science.gov (United States)

    ... use of certain legal and illegal drugs, or morbid obesity can lead to nephrotic syndrome. Symptoms Some kids ... KidsHealth® is for educational purposes only. For specific medical advice, diagnoses, and treatment, consult your doctor. © 1995- The Nemours Foundation. All ...

  15. Robinow Syndrome

    Directory of Open Access Journals (Sweden)

    Gökhan Gökalp

    2010-05-01

    Full Text Available Introduction: Robinow syndrome is characterized by dwarfism demonstrating short-limbed extremities, vertebral malsegmentation/malformation (hemivertebra, costal dysplasia, genital hypoplasia, and fetal facial appearance (wide and prominent forehead, hypertelorism, small and wide nose, molar hypoplasia, and retrognathia. It is a rare genetic disease which may present with either mild autosomal dominant form or severe recessive form. Vertebral and costal abnormalities are common diagnostic signs that may be severe. The disease presents with kyphoscoliosis and chest abnormalities along with thoracic vertebral fusion and hemivertebral appearance. Ribs may demonstrate fusion. Based on those involvements, the disease can be categorized as spondylothoracic, spondylocostal, ischiovertebral dysplasia, and cervicofaciothoracic syndrome.Diagnosis is established by the help of clinical characteristics. Radiography might contribute to the diagnosis by revealing changes in the skeletal system. Case Report: A three-year-old male patient presented with operated left undescendent testis and buried penis. On physical examination, he also had a dysmorphic face characterized by macrocephaly, hypertelorism, prominent eyes, a flattened nasal bridge, triangular-fish mouth, gingival hypertrophy and left hand clinodactyly. Radiographic examination documented mesomelic shortening of the radius-ulna, malsegmentation of the thoracal spine and the ribs fusion.Conclusion: Robinow syndrome is a rare syndrome which can be diagnosed by typical facial appearance and radiologic findings. (Journal of Current Pediatrics 2010; 8: 44-7

  16. Rett Syndrome.

    Science.gov (United States)

    Culbert, Linda A.

    This pamphlet reviews the historical process involved in initially recognizing Rett Syndrome as a specific disorder in girls. Its etiology is unknown, but studies have considered factors as hyperammonemia, a two-step mutation, a fragile X chromosome, metabolic disorder, environmental causation, dopamine deficiency, and an inactive X chromosome.…

  17. Nodding Syndrome

    Centers for Disease Control (CDC) Podcasts

    2013-12-19

    Dr. Scott Dowell, a CDC director, discusses the rare illness, nodding syndrome, in children in Africa.  Created: 12/19/2013 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 1/27/2014.

  18. Usher Syndrome

    Science.gov (United States)

    ... of their hearing within the first year of life. Progressive vision loss caused by retinitis pigmentosa becomes occurs in childhood. ... type III have progressive hearing loss and vision loss beginning in the first few decades of life. Unlike the other forms of Usher syndrome, infants ...

  19. [Refeeding syndrome].

    Science.gov (United States)

    Ševela, Stanislav; Novák, František; Kazda, Antonín; Brodská, Helena

    2016-01-01

    Despite being known more than 60 years, refeeding syndrome (RS) still bears many uncertainties. For example, its definition is not clear and definite, and the attitude to it varies from the complete neglect to over-prevention.The term "refeeding syndrome" refers to electrolyte and metabolic changes occurring in malnourished patients after the readministration of nutrition. These changes concern especially to phosphates and ions. Potassium, magnesium, naturism and fluids balance are involved. The changes lead to cell energetic metabolism and electric potential disturbances, with related clinical symptoms.Fully developed refeeding syndrome is quite rare; nevertheless it can be fatal for the patient. However, even its development can lead to many complications increasing the patient's morbidity and the length of stay in the hospital. Yet the refeeding syndrome is more or less predictable and if kept in mind also preventable.The aim of this article is to get the reader to know more about this metabolic phenomenon and possible attitudes towards it. PMID:27088791

  20. Noonan syndrome.

    NARCIS (Netherlands)

    Burgt, I. van der

    2007-01-01

    Noonan Syndrome (NS) is characterised by short stature, typical facial dysmorphology and congenital heart defects. The incidence of NS is estimated to be between 1:1000 and 1:2500 live births. The main facial features of NS are hypertelorism with down-slanting palpebral fissures, ptosis and low-set

  1. Metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    Charles Shaeffer

    2004-01-01

    @@ The emergence of cardiac disease as the number one world-wide cause of death justifies efforts to identify individuals at higher risk for preventive therapy. The metabolic syndrome, originally described by Reaven, 1 has been associated with higher cardiovascular disease risk. 2 Type Ⅱ diabetes is also a frequent sequela. 3

  2. Tourette Syndrome

    Science.gov (United States)

    ... writing, painting, or making music help focus the mind on other things. There's speculation that the composer Mozart had TS. Find support. The Tourette Syndrome Association sponsors support groups with others who understand the challenges of TS. Take control. People with TS can feel more in control ...

  3. Lemierre's syndrome

    DEFF Research Database (Denmark)

    Johannesen, Katrine; Bødtger, Uffe; Heltberg, Ole

    2014-01-01

    a variety of infectious complications. Rapid diagnosis and treatment is necessary to avoid severe complications or death. Close collaboration with local microbiologist is pivotal. Treatment consists of longterm treatment with penicillin and metronidazole. This is a case report of Lemierre's syndrome....

  4. Marfan syndrome masked by Down syndrome?

    OpenAIRE

    Mulder, B. J.; van Engelen, K.; Vis, J.C.; Timmermans, J.; Hamel, B C J

    2009-01-01

    Down syndrome is the most common chromosomal abnormality. A simultaneous occurrence with Marfan syndrome is extremely rare. We present a case of a 28-year-old female with Down syndrome and a mutation in the fibrillin-1 gene. The patient showed strikingly few manifestations of Marfan syndrome. Although variable expression is known to be present in Marfan syndrome, phenotypic expression of Marfan syndrome in our patient might be masked by the co-occurrence of Down syndrome. (Neth Heart J 2009;1...

  5. Schnitzler syndrome: clinical features and histopathology

    OpenAIRE

    Dingli, David

    2015-01-01

    David Dingli,1,2 Michael J Camilleri3 1Division of Hematology, Department of Internal Medicine, 2Department of Molecular Medicine, 3Department of Dermatology, Mayo Clinic, Rochester, MN, USA Abstract: Schnitzler syndrome is a rare and underrecognized syndrome characterized by chronic urticaria, a monoclonal protein, and a variety of other symptoms, including fever, bone pain, organomegaly, and evidence of an acute phase response. Biopsy of an involved area of the skin shows a neutrophilic in...

  6. Contemporary management of acute coronary syndrome

    OpenAIRE

    Large, G

    2005-01-01

    This review focuses on the modern management of the non-ST elevation acute coronary syndromes (unstable angina and non-ST elevation myocardial infarction). Patients with these syndromes are at varying degrees of risk of (re)infarction and death. This risk can be reliably predicted by clinical, electrocardiographic, and biochemical markers. Aspirin, clopidogrel, heparin (unfractionated or low molecular weight), and anti-ischaemic drugs should be offered to all patients, irrespective of the pre...

  7. J Wave Syndromes: A Decade of Progress

    Institute of Scientific and Technical Information of China (English)

    Guo-Liang Li; Lin Yang; Chang-Cong Cui; Chao-Feng Sun; Gan-Xin Yan

    2015-01-01

    Objective:The objective was to provide a brief history of J wave syndromes and to summarize our current understanding of their molecular,ionic,cellular mechanisms,and clinical features.We will also discuss the existing debates and further direction in basic and clinical research for J wave syndromes.Data Sources:The publications on key words of"J wave syndromes","early repolarization syndrome (ERS)","Brugada syndrome (BrS)" and "ST-segment elevation myocardial infarction (STEMI)" were comprehensively reviewed through search of the PubMed literatures without restriction on the publication date.Study Selection:Original articles,reviews and other literatures concerning J wave syndromes,ERS,BrS and STEMI were selected.Results:J wave syndromes were firstly defined by Yan et al.in a Chinese journal a decade ago,which represent a spectrum of variable phenotypes characterized by appearance of prominent electrocardiographic J wave including ERS,BrS and ventricular fibrillation (VF) associated with hypothermia and acute STEMI.J wave syndromes can be inherited or acquired and are mechanistically linked to amplification of the transient outward current (Ito)-mediated J waves that can lead to phase 2 reentry capable of initiating VF.Conclusions:J wave syndromes are a group of newly highlighted clinical entities that share similar molecular,ionic and cellular mechanism and marked by amplified J wave on the electrocardiogram and a risk of VF.The clinical challenge ahead is to identify the patients with J wave syndromes who are at risk for sudden cardiac death and determine the alternative therapeutic strategies to reduce mortality.

  8. J Wave Syndromes: A Decade of Progress

    Directory of Open Access Journals (Sweden)

    Guo-Liang Li

    2015-01-01

    Full Text Available Objective: The objective was to provide a brief history of J wave syndromes and to summarize our current understanding of their molecular, ionic, cellular mechanisms, and clinical features. We will also discuss the existing debates and further direction in basic and clinical research for J wave syndromes. Data Sources: The publications on key words of "J wave syndromes", "early repolarization syndrome (ERS", "Brugada syndrome (BrS" and "ST-segment elevation myocardial infarction (STEMI" were comprehensively reviewed through search of the PubMed literatures without restriction on the publication date. Study Selection: Original articles, reviews and other literatures concerning J wave syndromes, ERS, BrS and STEMI were selected. Results: J wave syndromes were firstly defined by Yan et al. in a Chinese journal a decade ago, which represent a spectrum of variable phenotypes characterized by appearance of prominent electrocardiographic J wave including ERS, BrS and ventricular fibrillation (VF associated with hypothermia and acute STEMI. J wave syndromes can be inherited or acquired and are mechanistically linked to amplification of the transient outward current (I to -mediated J waves that can lead to phase 2 reentry capable of initiating VF. Conclusions: J wave syndromes are a group of newly highlighted clinical entities that share similar molecular, ionic and cellular mechanism and marked by amplified J wave on the electrocardiogram and a risk of VF. The clinical challenge ahead is to identify the patients with J wave syndromes who are at risk for sudden cardiac death and determine the alternative therapeutic strategies to reduce mortality.

  9. Role of reactive oxygen species in pathogenesis of nephrotic syndrome

    OpenAIRE

    Ghodake, Santoshi R.; Suryakar, A. N.; Ankush, R. D.; Shaikh, K.; Katta, A. V.

    2010-01-01

    Nephrotic syndrome is the common chronic disorder characterized by alteration of permeability of the glomerular capillary wall, resulting in its inability to restrict the urinary loss of proteins. Nephrotic syndrome is characterized by heavy proteinuria, hypoalbuminemia, hyperlipidemia associated with peripheral edema. The molecular basis of glomerular permselectivity remains largely unknown. In recent years it has been proposed that Nephrotic syndrome is a consequence of an imbalance between...

  10. Unbalanced 13;18 translocation and Williams syndrome.

    OpenAIRE

    COLLEY, A.; Thakker, Y; Ward, H.; Donnai, D

    1992-01-01

    A 2 1/2 year old girl is reported with a de novo 13;18 unbalanced translocation and the facial features of Williams syndrome, subaortic stenosis, failure to thrive, and developmental delay. This case provides two candidate locations for the underlying molecular pathology of this sporadic syndrome. Williams syndrome is associated with intellectual and growth retardation, infantile feeding problems which may be associated with hypercalcaemia, cardiovascular abnormalities, a friendly, loquacious...

  11. Paraneoplastic syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1994-03-01

    Paraneoplastic syndromes (PNS) comprise a diverse group of disorders that are associated with cancer but unrelated to the size, location, metastases, or physiologic activities of the mature tissue of origin. They are remote effects of tumors that may appear as signs, symptoms, or syndromes which can mimic other disease conditions encountered in veterinary medicine. Recognition of PNS is valuable for several reasons: the observed abnormalities may represent tumor cell markers and facilitate early diagnosis of the tumor; they may allow assessment of premalignant states; they may aid in the search metastases; they may help quantify and monitor response to therapy; and, they may provide insight into the study of malignant transformation and oncogene expression. This review will concentrate on the pathophysiology, diagnosis, and treatment of some of the common PNS encountered in veterinary medicine.

  12. Waardenburg syndrome

    OpenAIRE

    Mehta, Manish; Kavadu, Paresh; Chougule, Sachin

    2004-01-01

    We report a case of Waardenburg syndrome in a female child aged 2yrs. Petrus Johannes Waardenburg(1) , a Dutch Ophthalmologist in 1951 described individuals with retinal pigmentary differences who had varying degrees of hearing loss and dystopia canthorum (i.e., latral displacement of inner canthi of eyes). The disease runs in families with a dominant inheritance pattern with varying degree of clinical presentation. Patient usually present with heterochromic iris, pigmentary abnormalities of ...

  13. Waardenburg syndrome

    OpenAIRE

    Tagra Sunita; Talwar Amrita; Walia Rattan Lal; Sidhu Puneet

    2006-01-01

    Waardenburg syndrome is a rare inherited and genetically heterogenous disorder of neural crest cell development. Four distinct subtypes showing marked interfamilial and intrafamilial variability have been described. We report a girl showing constellation of congenital hearing impairment with 110 dB and 105 dB loss in right and left ear respectively, hypoplastic blue iridis, white forelock, dystopia canthorum and broad nasal root. Other affected relatives of the family, with variable features ...

  14. HABERLAND SYNDROME

    Directory of Open Access Journals (Sweden)

    Ratnakumari

    2014-08-01

    Full Text Available Encephalo cranio cutaneous lipomatosis (ECCL is a rare neuro-cutaneous syndrome. It is characterized by unilateral lipomas of the cranium, face, and neck, ipsilateral lipodermoids of the eye, ipsilateral brain anomalies. There are 53 cases mentioned so far in the literature. To our knowledge, only 3 cases were reported from India. We report a case of a baby girl who presented in our institution for neuro-radiological evaluation based on which diagnosis of ECCL was made.

  15. Turner Syndrome

    OpenAIRE

    Akcan AB.

    2007-01-01

    Turner syndrome (TS) is a neurogenetic disorder characterized by partial or complete monosomy-X. TS is associated with certain physical and medical features including estrogen deficiency, short stature and increased risk for several diseases with cardiac conditions being among the most serious. Girls with TS are typically treated with growth hormone and estrogen replacement therapies to address short stature and estrogen deficiency. The cognitive-behavioral phenotype associated with TS includ...

  16. Robinow Syndrome

    OpenAIRE

    Gökhan Gökalp; Erdal Eren; Zeynep Yazıcı; Halil Sağlam

    2010-01-01

    Introduction: Robinow syndrome is characterized by dwarfism demonstrating short-limbed extremities, vertebral malsegmentation/malformation (hemivertebra), costal dysplasia, genital hypoplasia, and fetal facial appearance (wide and prominent forehead, hypertelorism, small and wide nose, molar hypoplasia, and retrognathia). It is a rare genetic disease which may present with either mild autosomal dominant form or severe recessive form. Vertebral and costal abnormalities are common diagnostic si...

  17. Marfan syndrome.

    OpenAIRE

    Jain, Eesha; Pandey, Ramesh Kumar

    1997-01-01

    Marfan syndrome is a rare autosomal dominant disorder of the connective tissue, with skeletal, ligamentous, orooculofacial, pulmonary, abdominal, neurological and the most fatal, cardiovascular manifestations. It has no cure but early diagnosis, regular monitoring and preventive lifestyle regimen ensure a good prognosis. However, the diagnosis can be difficult as it is essentially a clinical one, relying on family history, meticulous physical examination and investigation of involved organ sy...

  18. Mermaid syndrome

    OpenAIRE

    Çelik, Yalçın; Turhan, Ali Haydar; Gülaşı, Selvi; Kara, Tuğba; Şenli, Hicran; Atıcı, Aytuğ

    2013-01-01

    Sirenomelia also known as the mermaid syndrome is a very rare congenital anomaly characterized by lower limb fusion and severe urogenital gastrointestinal cardiovasculer central nervous system malformations We report a case of sirenomelia who had a single umblical artery renal agenesis pulmoner hypoplasia esophageal atresia ventricular septal defect anal atresia intestinal atresia and who was lost at fifth hour of life Turk Arch Ped 2013; 48: 65 7

  19. Noonan Syndrome

    OpenAIRE

    Bhambhani, Vikas; Muenke, Maximilian

    2014-01-01

    Noonan syndrome is a common genetic disorder that causes multiple congenital abnormalities and a large number of potential health conditions. Most affected individuals have characteristic facial features that evolve with age; a broad, webbed neck; increased bleeding tendency; and a high incidence of congenital heart disease, failure to thrive, short stature, feeding difficulties, sternal deformity, renal malformation, pubertal delay, cryptorchidism, developmental or behavioral problems, visio...

  20. Apert's Syndrome

    OpenAIRE

    Kumar, Gudipaneni Ravi; Jyothsna, Mandapati; Ahmed, Syed Basheer; Sree Lakshmi, Ketham Reddy

    2014-01-01

    ABSTRACT Apert's syndrome (acrocephalosyndactyly) is a rare congenital disorder characterized by craniosynostosis, midfacial malforma­tion and symmetrical syndactyly of hands and feet. Craniofacial deformities include cone-shaped calvarium, fat forehead, prop-tosis, hypertelorism and short nose with a bulbous tip. Intraoral findings include high arched palate with pseudocleft, maxillary transverse and sagittal hypoplasia with concomitant dental crowding, skeletal and dental anterior open bite...

  1. Hepatorenal syndrome

    Institute of Scientific and Technical Information of China (English)

    Sharon Turban; Paul J Thuluvath; Mohamed G Atta

    2007-01-01

    Hepatorenal syndrome (HRS) is a "functional" and reversible form of renal failure that occurs in patients with advanced chronic liver disease. The distinctive hallmark feature of HRS is the intense renal vasoconstriction caused by interactions between systemic and portal hemodynamics. This results in activation of vasoconstrictors and suppression of vasodilators in the renal circulation. Epidemiology, pathophysiology, as well as current and emerging therapies of HRS are discussed in this review.

  2. Brachycephalic Syndrome.

    Science.gov (United States)

    Dupré, Gilles; Heidenreich, Dorothee

    2016-07-01

    Animals presenting with brachycephalic syndrome suffer from multilevel obstruction of the airways as well as secondary structural collapse. Stenotic nares, aberrant turbinates, nasopharyngeal collapse, soft palate elongation and hyperplasia, laryngeal collapse, and left bronchus collapse are being described as the most common associated anomalies. Rhinoplasty and palatoplasty as well as newer surgical techniques and postoperative care strategies have resulted in significant improvement of the prognosis even in middle-aged dogs. PMID:27012936

  3. Caroli's syndrome

    International Nuclear Information System (INIS)

    In 1958 Caroli described the syndrome of congenital, either segmental or involving the entire bile duct system, saccular extensions of the intrahepatic bile ducts. He differentiated between two types of this disease pattern. The first form concerns pure cystic dilatations of the intrahepatic bile ducts, whereas the second one is combined with hepatic fibrosis and portal hypertension. Both types are characterised by cystic dilatations in the kidneys and in the extrahepatic bile ducts, pancreas and spleen. (orig.)

  4. Griscelli syndrome

    Directory of Open Access Journals (Sweden)

    Kumar T

    2006-01-01

    Full Text Available Partial albinism with immunodeficiency is a rare and fatal immunologic disorder characterized by pigmentary dilution and variable cellular immunodeficiency. It was initially described in 1978. Primary abnormalities included silvery grayish sheen to the hair, large pigment agglomerations in hair shafts and an abundance of mature melanosomes in melanocytes, with reduced pigmentation of adjacent keratinocytes. We describe a child with Griscelli syndrome who presented with hepatitis, pancytopenia and silvery hair. The diagnosis was confirmed by microscopic skin and hair examination.

  5. Asperger syndrome

    OpenAIRE

    Woodbury-Smith, Marc R.; Volkmar, Fred R.

    2008-01-01

    Abstract Asperger syndrome (AS) is a chronic neurodevelopmental disorder of social interaction, communication, and a restricted range of behaviors or interests. Although not generally associated with intellectual disability, the severe social disability and, in many cases, associated mental health and other medical problems, result in disability throughout life. The diagnosis is often delayed, sometimes into adulthood, which is unfortunate because there are now a range...

  6. Brugada syndrome

    Directory of Open Access Journals (Sweden)

    Rachel Bastiaenen

    2011-12-01

    Full Text Available The Brugada syndrome demonstrates characteristic electrocardiogram features and is a significant cause of sudden death in young adults with overtly normal cardiac structure and function. The genetic basis has not yet been fully elucidated but our understanding of the causative mutations and modifiers of arrhythmic events is advancing rapidly alongside sequencing technologies. We expect that the future will include risk stratification according to genotype and management tailored to the genetic diagnosis.

  7. Burnout syndrome

    Czech Academy of Sciences Publication Activity Database

    Kebza, V.; Šolcová, Iva

    Praha: EFPA/UPA, 2007 - (Polišenská, V.; Šolc, M.; Kotrlová, J.). s. 31 ISBN 978-80-7064-017-3. [European Conress of Psychology /10./. 03.07.2007-06.07.2007, Praha] R&D Projects: GA ČR GA406/06/0747 Institutional research plan: CEZ:AV0Z70250504 Keywords : burnout syndrome * type D personality * physiological indicators Subject RIV: AN - Psychology

  8. CREST Syndrome

    Directory of Open Access Journals (Sweden)

    Tuğçe Köksüz

    2014-06-01

    Full Text Available We report a case of CREST syndrome (calsinosis cutis, Raynaud’s phenomenon, oesophageal dysmotility, sclerodactyly and telangiectasia with all of the five major symptoms. A 46-year-old woman was admitted to our clinic with the complaint of erythema, rigidity and pain on the plantar surface of the feet. She had had Raynaud’s phenomenon for 20 years and oesophageal reflux for five years. Her face had become masklike and there was prominent telangiectasies on her face and hands. Sclerosis were confined to the fingers (sclerodactyly. Direct X-ray graphy demonstrated calcinosis cutis on the left hand and suprapatellar region. She was treated with nifedipine 30 mg/day, acetylsalicylic acid 100 mg/day for Raynaud’s phenomenon and famotidine 40 mg/day, metoclopramide HCL 30 mg/day for oesophageal dysmotility. Her complaints were partially relieved after the treatment. This case had all of the five major symptoms of CREST syndrome, and we aimed to emphasize the major symptoms and complications of CREST syndrome. (Turk J Dermatol 2012; 6: 48-50

  9. Antiphospholipid syndrome

    Directory of Open Access Journals (Sweden)

    Pavlović Dragan M.

    2010-01-01

    Full Text Available Antiphospholipid syndrome (APS is an autoimmune disease with recurrent thromboses and pregnancy complications (90% are female patients that can be primary and secondary (with concomitant autoimmune disease. Antiphospholipid antibodies are prothrombotic but also act directly with brain tissue. One clinical and one laboratory criterion is necessary for the diagnosis of APS. Positive serological tests have to be confirmed after at least 12 weeks. Clinical picture consists of thromboses in many organs and spontaneous miscarriages, sometimes thrombocytopaenia and haemolytic anaemia, but neurological cases are the most frequent: headaches, stroke, encephalopathy, seizures, visual disturbances, Sneddon syndrome, dementia, vertigo, chorea, balism, transitory global amnesia, psychosis, transversal myelopathy and Guillain-Barre syndrome. About 50% of strokes below 50 years of age are caused by APS. The first line of therapy in stroke is anticoagulation: intravenous heparin or low-weight heparins. In chronic treatment, oral anticoagulation and antiplatelet therapy are used, warfarin and aspirin, mostly for life. In resistant cases, corticosteroids, intravenous immunoglobulins and plasmapheresis are necessary. Prognosis is good in most patients but some are treatment-resistant with recurrent thrombotic events and eventually death.

  10. National Down Syndrome Society

    Science.gov (United States)

    ... with Down Syndrome Since 1979 National Down Syndrome Society 8 E 41st Street, 8th Floor New York ... Program! The mission of the National Down Syndrome Society is to be the national advocate for the ...

  11. Central Pain Syndrome

    Science.gov (United States)

    ... Enhancing Diversity Find People About NINDS NINDS Central Pain Syndrome Information Page Table of Contents (click to ... being done? Clinical Trials Organizations What is Central Pain Syndrome? Central pain syndrome is a neurological condition ...

  12. Fetal Alcohol Syndrome

    Science.gov (United States)

    ... Condiciones Chinese Conditions Fetal Alcohol Syndrome Read in Chinese What is Fetal Alcohol Syndrome (FAS)? Fetal Alcohol Syndrome (FAS) describes changes in a baby born to a mother whose pregnancy was complicated by alcohol consumption. A broader term ...

  13. Tourette Syndrome (For Parents)

    Science.gov (United States)

    ... their child cope with the condition. About Tourette Syndrome Tourette syndrome (TS) is named for French doctor Georges ... people with TS. previous continue Diagnosing and Treating Tourette Syndrome Pediatricians and family doctors may refer a child ...

  14. Barth Syndrome (BTHS)

    Science.gov (United States)

    ... Awards Enhancing Diversity Find People About NINDS NINDS Barth Syndrome Information Page Table of Contents (click to jump ... is being done? Clinical Trials Organizations What is Barth Syndrome? Barth syndrome (BTHS) is a rare, genetic disorder ...

  15. Sexuality and Down Syndrome

    Science.gov (United States)

    ... NDSS Home » Resources » Wellness » Sexuality » Sexuality & Down Syndrome Sexuality & Down Syndrome Human sexuality encompasses an individual's self- ... community standards for adult behavior. How Can Healthy Sexuality be Encouraged for Individuals with Down Syndrome? Creating ...

  16. Narcotic Bowel Syndrome

    Science.gov (United States)

    ... Intolerance Malabsorption Narcotic Bowel Syndrome Radiation Therapy Injury Short Bowel Syndrome Symptoms & Causes Treatments Nutrition and Diet Managing Secondary Effects Medications Surgery Daily Living with SBS Resources SMA Syndrome Volvulus ...

  17. J Wave Syndromes: Molecular and Cellular Mechanisms

    OpenAIRE

    Antzelevitch, Charles

    2013-01-01

    An early repolarization (ER) pattern in the ECG, consisting of J point elevation, distinct J wave with or without ST segment elevation or slurring of the terminal part of the QRS, was long considered a benign electrocardiographic manifestation. Experimental studies a dozen years ago suggested that an ER is not always benign, but may be associated with malignant arrhythmias. Validation of this hypothesis derives from recent case-control and population-based studies showing that an ER pattern i...

  18. Fraser syndrome and cryptophthalmos: review of the diagnostic criteria and evidence for phenotypic modules in complex malformation syndromes

    OpenAIRE

    Slavotinek, A; Tifft, C

    2002-01-01

    Fraser syndrome is characterised by cryptophthalmos, cutaneous syndactyly, malformations of the larynx and genitourinary tract, craniofacial dysmorphism, orofacial clefting, mental retardation, and musculoskeletal anomalies. The inheritance is autosomal recessive. No diagnostic cytogenetic abnormalities have been documented in affected patients, and no molecular genetic studies have been reported. We have reviewed 117 cases diagnosed as Fraser syndrome or cryptophthalmos published since the c...

  19. Chronic radiation syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Akleyev, Alexander V. [Urals Research Centre for Radiation Medicine, Chelyabinsk (Russian Federation). Clinical Dept.

    2014-04-01

    Comprehensive analysis of chronic radiation syndrome, covering epidemiology, pathogenesis, pathoanatomy, diagnosis and treatment. Based on observations in a unique sample of exposed residents of the Techa riverside villages in the Urals. Casts new light on the condition. Of value for all practitioners and researchers with an interest in chronic radiation syndrome. This book covers all aspects of chronic radiation syndrome (CRS) based on observations in a unique sample of residents of the Techa riverside villages in the southern Urals who were exposed to radioactive contamination in the 1950s owing to releases of liquid radioactive wastes from Mayak Production Association, which produced plutonium for weapons. In total, 940 cases of CRS were diagnosed in this population and these patients were subjected to detailed analysis. The opening chapters address the definition and classification of CRS, epidemiology and pathogenesis, covering molecular and cellular mechanisms, radioadaptation, and the role of tissue reactions. The pathoanatomy of CRS during the development and recovery stages is discussed for all organ systems. Clinical manifestations of CRS at the different stages are then described in detail and the dynamics of hematopoietic changes are thoroughly examined. In the following chapters, principles of diagnosis (including assessment of the exposure doses to critical organs) and differential diagnosis from a wide range of other conditions are discussed and current and potential treatment options, described. The medical and social rehabilitation of persons with CRS is also covered. This book, which casts new light on the condition, will be of value for all practitioners and researchers with an interest in CRS.

  20. Brittle cornea syndrome: a case report and comparison with Ehlers Danlos syndrome.

    Science.gov (United States)

    Ramappa, Muralidhar; Wilson, M Edward; Rogers, R Curtis; Trivedi, Rupal H

    2014-10-01

    We report a 6-week-old white boy of nonconsanguineous parents who presented with bluish scleral discoloration, thin corneas, and progressive high myopia. A diagnosis of brittle cornea syndrome was confirmed by molecular analysis and prompt measures were taken to manage the condition. Long-term follow-up of children diagnosed with brittle cornea syndrome is important to minimize the risks of corneal rupture and for detecting late-onset systemic conditions. PMID:25266838

  1. Hepatorenal syndrome

    Institute of Scientific and Technical Information of China (English)

    Jan Lata

    2012-01-01

    Hepatorenal syndrome (HRS) is defined as a functional renal failure in patients with liver disease with portal hypertension and it constitutes the climax of systemic circulatory changes associated with portal hypertension.This term refers to a precisely specified syndrome featuring in particular morphologically intact kidneys,where regulatory mechanisms have minimised glomerular filtration and maximised tubular resorption and urine concentration,which ultimately results in uraemia.The syndrome occurs almost exclusively in patients with ascites.Type 1 HRS develops as a consequence of a severe reduction of effective circulating volume due to both an extreme splanchnic arterial vasodilatation and a reduction of cardiac output.Type 2 HRS is characterised by a stable or slowly progressive renal failure so that its main clinical consequence is not acute renal failure,but refractory ascites,and its impact on prognosis is less negative.Liver transplantation is the most appropriate therapeutic method,nevertheless,only a few patients can receive it.The most suitable "bridge treatments" or treatment for patients ineligible for a liver transplant include terlipressin plus albumin.Terlipressin is at an initial dose of 0.5-1 mg every 4 h by intravenous bolus to 3 mg every 4 h in cases when there is no response.Renal function recovery can be achieved in less than 50% of patients and a considerable decrease in renal function may reoccur even in patients who have been responding to therapy over the short term.Transjugular intrahepatic portosystemic shunt plays only a marginal role in the treatment of HRS.

  2. Morvan Syndrome

    Science.gov (United States)

    Maskery, Mark; Chhetri, Suresh K.; Dayanandan, Rejith; Gall, Claire

    2016-01-01

    A 74-year-old gentleman was admitted to the regional neurosciences center with encephalopathy, myokymia, and dysautonomia. Chest imaging had previously identified an incidental mass in the anterior mediastinum, consistent with a primary thymic tumor. Antivoltage-gated potassium channel (anti-VGKC) antibodies were positive (titer 1273 pmol/L) and he was hypokalemic. Electromyogram and nerve conduction studies were in keeping with peripheral nerve hyperexcitability syndrome, and an electroencephalogram was consistent with encephalopathy. A diagnosis of Morvan syndrome was made, for which he was initially treated with high-dose steroids, followed by a 5-day course of intravenous immunoglobulin (IVIG) therapy. He also underwent thymectomy, followed by a postexcision flare of his symptoms requiring intensive care management. Further steroids, plasmapheresis, and IVIG achieved stabilization of his clinical condition, enabling transfer for inpatient neurorehabilitation. He was commenced on azathioprine and a prolonged oral steroid taper. A subsequent presumed incipient relapse responded well to further IVIG treatment. This case report documents a thymoma-associated presentation of anti-VGKC-positive Morvan syndrome supplemented by patient and carer narrative and video, both of which provide valuable further insights into this rare disorder. There are a limited number of publications surrounding this rare condition available in the English literature. This, combined with the heterogenous presentation, association with underlying malignancy, response to treatment, and prognosis, provides a diagnostic challenge. However, the association with anti-VGKC antibody-associated complexes and 2 recent case series have provided some scope for both accurate diagnosis and management. PMID:26740856

  3. Fragile X Syndrome

    Directory of Open Access Journals (Sweden)

    Wilmar Saldarriaga

    2015-01-01

    Full Text Available Fragile X Syndrome (FXS is a genetic disease due to a CGG trinucleotide expansion, named full mutation (greater than 200 CGG repeats, in the fragile X mental retardation 1 gene locus Xq27.3; which leads to an hypermethylated region in the gene promoter therefore silencing it and lowering the expression levels of the fragile X mental retardation 1, a protein involved in synaptic plasticity and maturation.  Individuals with FXS present with intellectual disability, autism, hyperactivity, long face, large or prominent ears and macroorchidism at puberty and thereafter. Most of the young children with FXS will present with language delay, sensory hyper arousal and anxiety. Girls are less affected than boys, only 25% have intellectual disability. Given the genomic features of the syndrome, there are patients with a number of triplet repeats between 55 and 200, known as premutation carriers. Most carriers have a normal IQ but some have developmental problems. The diagnosis of FXS has evolved from karyotype with special culture medium, to molecular techniques that are more sensitive and specific including PCR and Southern Blot. During the last decade, the advances in the knowledge of FXS, has led to the development of investigations on pharmaceutical management or targeted treatments for FXS. Minocycline and sertraline have shown efficacy in children.

  4. Trichorhinophalangeal syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Tuzovic, S.; Fiebach, B.J.O.; Magnus, L.; Sauerbrei, H.U.

    1982-11-01

    This article reports on 14 cases of a trichorhinophalangeal syndrome in five successive generations. Besides the well-known characteristics of the TRPS the following symptoms observed in this family are new: Teething was considerably delayed, intelligence was reduced, and there were skin manifestations resembling eczema. Besides, struma colli and colitis ulcerosa were also observed. Subsequent observations have to clarify whether these symptoms are a facultative part of the TRPS pattern. The constant appearance of carriers of these characteristics during five generation points to dominant heredity.

  5. Olmsted Syndrome

    Directory of Open Access Journals (Sweden)

    Sirka C

    1999-01-01

    Full Text Available A 20-year-old Sikh man had palmoplantar keratoderma, flexion deformity of digits, universal alopecia, keratotic plaques at the angles of mouth, gluteal cleft, knees and dorsal aspects of the metacarpophalangeal joints of the hand; features of Olmsted syndrome. He had normal nails, teeth, oral mucosa and normal joint movements. Treatment with acitretin, 25mg/day for three and a half months, followed by 25mg once daily alternating with 50mg once daily for 3 months resulted in significant improvement.

  6. [Piriformis syndrome].

    Science.gov (United States)

    Erauso, Thomas; Pégorie, Anne; Gaveau, Yves-Marie; Tardy, Dominique

    2010-09-20

    Sciatic pain is often misleading and establishing the link with a local muscular cause can be difficult and lead to errors, especially when faced with a young sportsman, with typical discogenic pain. Simple, specific and reproducible tests enable a better identification and treatment of a muscular cause or canal syndrome. Physiotherapy, or local infiltrations are generally very efficient, and sufficient. Surgery may be considered only in a very limited number of cases, lack of response to the first line treatment and then only if it is the absolute diagnosis, diagnosis which must remain a diagnosis of exception, more so of exclusion. PMID:21033479

  7. CREST Syndrome

    OpenAIRE

    Tuğçe Köksüz; Zeynep Nurhan Saraçoğlu; Ayşe Esra Koku-Aksu; İlham Sabuncu; Cengiz Korkmaz

    2014-01-01

    We report a case of CREST syndrome (calsinosis cutis, Raynaud’s phenomenon, oesophageal dysmotility, sclerodactyly and telangiectasia) with all of the five major symptoms. A 46-year-old woman was admitted to our clinic with the complaint of erythema, rigidity and pain on the plantar surface of the feet. She had had Raynaud’s phenomenon for 20 years and oesophageal reflux for five years. Her face had become masklike and there was prominent telangiectasies on her face and hands. Sclerosis were ...

  8. Rett Syndrome

    OpenAIRE

    Sitholey, Prabhat; Agarwal, Vivek; Srivastava, Rohit

    2012-01-01

    Rett syndrome is one of the most common causes of complex disability in girls. It is characterized by early neurological regression that severely affects motor, cognitive and communication skills, by autonomic dysfunction and often a seizure disorder. It is a monogenic X-linked dominant neurodevelopmental disorder related to mutation in MECP2, which encodes the methyl-CpG-binding protein MeCP2. There are several mouse models either based on conditional knocking out of the Mecp2 gene or on a t...

  9. [Ascher's syndrome].

    Science.gov (United States)

    Halling, F; Sandrock, D; Merten, H A; Hönig, J F

    1991-01-01

    Ascher's syndrome is composed of the triad blepharochalasis, double lip and goitre. In many of the cases reported in the literature this typical constellation of symptoms is not complete; particularly the struma is not mandatorily involved. A 58-year-old patient with this rare disease who exhibited blepharochalasis and double upper and lower lip is presented. Additionally, subclinical hypothyroidism and alopecia areata totalis were found. In differential diagnosis other causes of double lips or enlargement of the lips must be considered. PMID:1817784

  10. Mazabraud syndrome

    Science.gov (United States)

    John, Anulekha Mary; Behera, Kishore Kumar; Mathai, Thomas; Parmar, Harshad; Paul, Thomas V.

    2013-01-01

    A 25 year old lady presented with pain and swelling of left thigh. On examination she was found to have tenderness of left femur with a separate soft tissue swelling within the thigh muscle. Further evaluation revealed expansile bony lesion on X-ray of left tibia and multiple hot spots on bone scan suggestive of fibrous dysplasia. The soft tissue swelling on excision and histopathological examination was found to be intramuscular myxoma. The combination of the above two, called Mazabraud syndrome is being reported. PMID:23961498

  11. Mazabraud syndrome

    Directory of Open Access Journals (Sweden)

    Anulekha Mary John

    2013-01-01

    Full Text Available A 25 year old lady presented with pain and swelling of left thigh. On examination she was found to have tenderness of left femur with a separate soft tissue swelling within the thigh muscle. Further evaluation revealed expansile bony lesion on X-ray of left tibia and multiple hot spots on bone scan suggestive of fibrous dysplasia. The soft tissue swelling on excision and histopathological examination was found to be intramuscular myxoma. The combination of the above two, called Mazabraud syndrome is being reported.

  12. Griscelli syndrome.

    Science.gov (United States)

    Ariffin, H; Geikowski, A; Chin, T F; Chau, D; Arshad, A; Abu Bakar, K; Krishnan, S

    2014-08-01

    We report a case of Griscelli Syndrome (GS). Our patient initially presented with a diagnosis of haemophagocytic lymphistiocytosis (HLH). Subsequent microscopic analysis of the patient's hair follicle revealed abnormal distribution of melanosomes in the shaft, which is a hallmark for GS. Analysis of RAB27A gene in this patient revealed a homozygous mutation in exon 6, c.550C>T, p.R184X . This nonsense mutation causes premature truncation of the protein resulting in a dysfunctional RAB27A. Recognition of GS allows appropriate institution of therapy namely chemotherapy for HLH and curative haemotopoeitic stem cell transplantation. PMID:25500851

  13. HELLP syndrome

    Directory of Open Access Journals (Sweden)

    Dilek Acar

    2014-08-01

    Suggested treatment modality consists, stabilization of blood pressure and magnesium sulfate infusion. Then evaluation of fetal status and planning delivery method and time if maternal status remains unstable. If prognosis seems favorable without urgent delivery and fetus can benefit from it, a course of betamethasone can be given to fetuses between 24 and 34 weeks of gestational age. The only and definite treatment of HELLP syndrome is delivering the baby. Suggested benefits of steroid therapy and other experimental treatments are still to be proven effective by large randomized controlled trials. [Archives Medical Review Journal 2014; 23(4.000: 735-760

  14. OCULO-CEREBRO-RENAL SYNDROME (LOWE'S SYNDROME)

    Institute of Scientific and Technical Information of China (English)

    1991-01-01

    Oculo-cerebro-renal syndrome (Lowe's syndrome) is characterized by mental and motor retardation, cataract, glaucoma and renal abnormalities. It is an X-linked recessive metabolic disease. Two brothers suffering from Lowe's syndrome are reported. Their mother with lenticular opacities and peculiar facial appearance is in concordance with the obligate carrier. The ocular changes and heridity are discussed.

  15. Polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Aziz, M; Naver, Klara; Wissing, Marie Louise Muff;

    2012-01-01

    Objectives: The primary objective of this multicenter study is to evaluate the relative impact of insulin resistance (IR) and body mass index (BMI) in women with polycystic ovary syndrome (PCOS) on (1) Key hemodynamic/thrombogenic variables, (2) Oocyte quality and early embryo development, (3...... inclusion: About 200 women fulfilling the Rotterdam Criteria and 100 women without PCOS recruited from 2010 to 2012. Methods: The impact of PCOS, as well as the impact of IR and BMI on the hormonal, metabolic and hemostatic key variables will be analyzed combining conventional, molecular techniques and...... biochemical markers of growth and inflammation and clinical pregnancy complications. Main outcome measures: Metabolic and hemostatic risk-biomarkers, oocyte and embryo quality, adverse pregnancy outcome, fetal growth and placental function in women with PCOS....

  16. [Hermansky-Pudlak syndrome].

    Science.gov (United States)

    Atili, A; Lübke, J; Shoukier, M; Schittkowski, M P

    2013-02-01

    A 1-year-old female child suffering from nystagmus and abnormal head posture (AHP) was presented by the parents in our clinic. The family history revealed the presence of von Willebrand's disease in both parents. General examination showed a female child with light blond colored skin accompanied by black-haired parents. Physical and ophthalmic examination revealed nystagmus, AHP and oculocutaneous albinism. The molecular genetic analysis showed a mutation in the HPS-1 gene which confirmed the suspected diagnosis of Hermansky-Pudlak syndrome (HPS). Of clinical significance, patients with HPS commonly have hemorrhagic diathesis, granulomatous colitis or restrictive lung fibrosis. A detailed full medical history, ophthalmic examination as well as genetic analyses are essential in establishing the diagnosis of HPS. Treatment includes correcting refraction anomalies with spectacles or contact lenses, prescription of tinted glasses or surgical correction of the AHP. An internal medical consultation is also necessary for the management of other associated symptoms, such as hemorrhagic diathesis. PMID:22806537

  17. 大前庭水管综合征的相关研究进展%The research progress of large vestibular aqueduct syndrome

    Institute of Scientific and Technical Information of China (English)

    阿布利克木·依明; 唐亮

    2012-01-01

    Large vestibuiar aqueduc syndrome (LVAS) is one of common non-syndromic hearing disorders. With the rapid development of medical imaging, audiology, molecular biology , genetics, cochlear implant surgery, we have made remarkable achievements in the diagnosis and treatment of large vestibular aqueduct syndrome. This article reviewed related researches of the large vestibular aqueduct syndrome.

  18. KBG syndrome

    Directory of Open Access Journals (Sweden)

    Brancati Francesco

    2006-12-01

    Full Text Available Abstract KBG syndrome is a rare condition characterised by a typical facial dysmorphism, macrodontia of the upper central incisors, skeletal (mainly costovertebral anomalies and developmental delay. To date, KBG syndrome has been reported in 45 patients. Clinical features observed in more than half of patients that may support the diagnosis are short stature, electroencephalogram (EEG anomalies (with or without seizures and abnormal hair implantation. Cutaneous syndactyly, webbed short neck, cryptorchidism, hearing loss, palatal defects, strabismus and congenital heart defects are less common findings. Autosomal dominant transmission has been observed in some families, and it is predominantly the mother, often showing a milder clinical picture, that transmits the disease. The diagnosis is currently based solely on clinical findings as the aetiology is unknown. The final diagnosis is generally achieved after the eruption of upper permanent central incisors at 7–8 years of age when the management of possible congenital anomalies should have been already planned. A full developmental assessment should be done at diagnosis and, if delays are noted, an infant stimulation program should be initiated. Subsequent management and follow-up should include an EEG, complete orthodontic evaluation, skeletal investigation with particular regard to spine curvatures and limb asymmetry, hearing testing and ophthalmologic assessment.

  19. Myasthenic syndromes.

    Science.gov (United States)

    Farrugia, M E

    2011-03-01

    The neuromuscular junction is vulnerable to autoimmune attack both at the pre-synaptic nerve terminal and at the post-synaptic muscle membrane. Antibodies directed to the nicotinic acetylcholine receptor at the muscle surface are the cause of myasthenia gravis in the majority of cases. Myasthenia gravis is an acquired condition, characterised by weakness and fatigability of the skeletal muscles. The ocular muscles are commonly affected first, but the disease often generalises. Treatment includes symptom control and immunosuppression. The thymus gland plays an important role in the pathogenesis of myasthenia gravis and thymectomy is indicated in certain subgroups. Lambert-Eaton myasthenic syndrome is associated with antibodies directed to the voltage-gated calcium channel antibodies at the pre-synaptic nerve terminal. It is an acquired condition and, in some cases, may be paraneoplastic, often secondary to underlying small cell lung carcinoma. Clinical presentation is distinct from myasthenia gravis, with patients often first presenting with lower limb muscle fatigability and autonomic symptoms. Congenital myasthenic syndromes are inherited neuromuscular disorders due to mutations in proteins at the neuromuscular junction. Various phenotypes exist depending on the protein mutation. Treatment is directed towards symptom control and immunosuppression is not indicated. PMID:21365067

  20. Marfan Syndrome (For Parents)

    Science.gov (United States)

    ... Tropical Delight: Melon Smoothie Pregnant? Your Baby's Growth Marfan Syndrome KidsHealth > For Parents > Marfan Syndrome Print A ... the Doctor en español Síndrome de Marfan About Marfan Syndrome Marfan syndrome is a progressive genetic disorder ...

  1. Facts about Down Syndrome

    Science.gov (United States)

    ... Us Information For... Media Policy Makers Facts about Down Syndrome Language: English Español (Spanish) Recommend on Facebook Tweet ... with Down syndrome. View charts » What is Down Syndrome? Down syndrome is a condition in which a ...

  2. Molecular physics

    CERN Document Server

    Williams, Dudley

    2013-01-01

    Methods of Experimental Physics, Volume 3: Molecular Physics focuses on molecular theory, spectroscopy, resonance, molecular beams, and electric and thermodynamic properties. The manuscript first considers the origins of molecular theory, molecular physics, and molecular spectroscopy, as well as microwave spectroscopy, electronic spectra, and Raman effect. The text then ponders on diffraction methods of molecular structure determination and resonance studies. Topics include techniques of electron, neutron, and x-ray diffraction and nuclear magnetic, nuclear quadropole, and electron spin reson

  3. Endocrine neoplasms in familial syndromes of hyperparathyroidism.

    Science.gov (United States)

    Li, Yulong; Simonds, William F

    2015-06-01

    Familial syndromes of hyperparathyroidism, including multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2A (MEN2A), and the hyperparathyroidism-jaw tumor (HPT-JT), comprise 2-5% of primary hyperparathyroidism cases. Familial syndromes of hyperparathyroidism are also associated with a range of endocrine and nonendocrine tumors, including potential malignancies. Complications of the associated neoplasms are the major causes of morbidities and mortalities in these familial syndromes, e.g., parathyroid carcinoma in HPT-JT syndrome; thymic, bronchial, and enteropancreatic neuroendocrine tumors in MEN1; and medullary thyroid cancer and pheochromocytoma in MEN2A. Because of the different underlying mechanisms of neoplasia, these familial tumors may have different characteristics compared with their sporadic counterparts. Large-scale clinical trials are frequently lacking due to the rarity of these diseases. With technological advances and the development of new medications, the natural history, diagnosis, and management of these syndromes are also evolving. In this article, we summarize the recent knowledge on endocrine neoplasms in three familial hyperparathyroidism syndromes, with an emphasis on disease characteristics, molecular pathogenesis, recent developments in biochemical and radiological evaluation, and expert opinions on surgical and medical therapies. Because these familial hyperparathyroidism syndromes are associated with a wide variety of tumors in different organs, this review is focused on those endocrine neoplasms with malignant potential. PMID:27207564

  4. Hamartomatous polyposis syndromes

    DEFF Research Database (Denmark)

    Jelsig, Anne Marie; Qvist, Niels; Brusgaard, Klaus;

    2014-01-01

    -intestinal symptoms and types of cancers differs.Clinical awareness and early diagnosis of HPS is important, as affected patients and at-risk family members should be offered genetic counselling and surveillance. Surveillance in children with HPS might prevent or detect intestinal or extra-intestinal complications......Hamartomatous Polyposis Syndromes (HPS) are genetic syndromes, which include Peutz-Jeghers syndrome, Juvenile polyposis syndrome, PTEN hamartoma tumour syndrome (Cowden Syndrom, Bannayan-Riley-Ruvalcaba and Proteus Syndrome) as well as hereditary mixed polyposis syndrome. Other syndromes such as......-intestinal cancer. The syndromes are rare and inherited in an autosomal dominant manner.The diagnosis of HPS has traditionally been based on clinical criteria, but can sometimes be difficult as the severity of symptoms range considerably from only a few symptoms to very severe cases - even within the same family...

  5. Superior Mesenteric Artery Syndrome or Wilkie Syndrome

    International Nuclear Information System (INIS)

    We described three cases of superior mesenteric artery (SMA) syndrome, also known as Wilkie's syndrome, chronic duodenal ileus, or cast syndrome. This syndrome occurs when the third portion of the duodenum is compressed between the SMA and the aorta. The major risk factors for development of SMA syndrome are rapid weight loss and surgical correction of spinal deformities. The clinical presentation of SMA syndrome is variable and nonspecific, including nausea, vomiting, abdominal pain, and weight loss. The diagnosis is based on endoscopic, radiographic and tomographic findings of duodenal compression by the SMA. The treatment of SMA syndrome is aimed at the precipitating factor, which usually is related to weight loss. Therefore, conservative therapy with nutritional supplementation is the initial approach, and surgery is reserved for those who do not respond to nutritional therapy.

  6. Applying molecular epidemiology in pediatric leukemia.

    Science.gov (United States)

    Schiffman, Joshua D

    2016-02-01

    Molecular epidemiology is the study of genetic and environmental risk for disease, with much effort centered on cancer. Childhood leukemia occurs in nearly a third of all patients newly diagnosed with pediatric cancer. only a small percentage of these new cases of childhood leukemia are associated with high penetrant hereditary cancer syndromes. Childhood leukemia, especially acute lymphoblastic leukemia, has been associated with a dysregulated immune system due to delayed infectious exposure at a young age. Identical twins with childhood leukemia suggest that acute lymphoblastic leukemia begins in utero and that the concordant presentation is due to a shared preleukemia subclone via placental transfer. Investigation of single nucleotide polymorphisms within candidate genes find that leukemia risk may be attributed to population-based polymorphisms affecting folate metabolism, xenobiotic metabolism, DNA repair, immunity, and B-cell development. More recently, genome-wide association studies for leukemia risk has led investigators to genes associated with B-cell development. When describing leukemia predisposition due to hereditary cancer syndromes, the following 6 categories become apparent on the basis of biology and clinical presentation: (1) genetic instability/DNA repair syndromes, (2) cell cycle/differentiation syndromes, (3) bone marrow failure syndromes, (4) telomere maintenance syndromes, (5) immunodeficiency syndromes, and (6) transcription factor syndromes and pure familial leukemia. understanding the molecular epidemiology of childhood leukemia can affect the treatment and tumor surveillance strategies for these high risk patients and their family members. PMID:25973690

  7. Leopard syndrome

    Directory of Open Access Journals (Sweden)

    Dallapiccola Bruno

    2008-05-01

    Full Text Available Abstract LEOPARD syndrome (LS, OMIM 151100 is a rare multiple congenital anomalies condition, mainly characterized by skin, facial and cardiac anomalies. LEOPARD is an acronym for the major features of this disorder, including multiple Lentigines, ECG conduction abnormalities, Ocular hypertelorism, Pulmonic stenosis, Abnormal genitalia, Retardation of growth, and sensorineural Deafness. About 200 patients have been reported worldwide but the real incidence of LS has not been assessed. Facial dysmorphism includes ocular hypertelorism, palpebral ptosis and low-set ears. Stature is usually below the 25th centile. Cardiac defects, in particular hypertrophic cardiomyopathy mostly involving the left ventricle, and ECG anomalies are common. The lentigines may be congenital, although more frequently manifest by the age of 4–5 years and increase throughout puberty. Additional common features are café-au-lait spots (CLS, chest anomalies, cryptorchidism, delayed puberty, hypotonia, mild developmental delay, sensorineural deafness and learning difficulties. In about 85% of the cases, a heterozygous missense mutation is detected in exons 7, 12 or 13 of the PTPN11 gene. Recently, missense mutations in the RAF1 gene have been found in two out of six PTPN11-negative LS patients. Mutation analysis can be carried out on blood, chorionic villi and amniotic fluid samples. LS is largely overlapping Noonan syndrome and, during childhood, Neurofibromatosis type 1-Noonan syndrome. Diagnostic clues of LS are multiple lentigines and CLS, hypertrophic cardiomyopathy and deafness. Mutation-based differential diagnosis in patients with borderline clinical manifestations is warranted. LS is an autosomal dominant condition, with full penetrance and variable expressivity. If one parent is affected, a 50% recurrence risk is appropriate. LS should be suspected in foetuses with severe cardiac hypertrophy and prenatal DNA test may be performed. Clinical management should

  8. Metabolic Syndrome: Polycystic Ovary Syndrome.

    Science.gov (United States)

    Mortada, Rami; Williams, Tracy

    2015-08-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous condition characterized by androgen excess, ovulatory dysfunction, and polycystic ovaries. It is the most common endocrinopathy among women of reproductive age, affecting between 6.5% and 8% of women, and is the most common cause of infertility. Insulin resistance is almost always present in women with PCOS, regardless of weight, and they often develop diabetes and metabolic syndrome. The Rotterdam criteria are widely used for diagnosis. These criteria require that patients have at least two of the following conditions: hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. The diagnosis of PCOS also requires exclusion of other potential etiologies of hyperandrogenism and ovulatory dysfunction. The approach to PCOS management differs according to the presenting symptoms and treatment goals, particularly the patient's desire for pregnancy. Weight loss through dietary modifications and exercise is recommended for patients with PCOS who are overweight. Oral contraceptives are the first-line treatment for regulating menstrual cycles and reducing manifestations of hyperandrogenism, such as acne and hirsutism. Clomiphene is the first-line drug for management of anovulatory infertility. Metformin is recommended for metabolic abnormalities such as prediabetes, and a statin should be prescribed for cardioprotection if the patient meets standard criteria for statin therapy. PMID:26280343

  9. [Hepatopulmonary syndrome].

    Science.gov (United States)

    Thévenot, Thierry; Weil, Delphine; Garioud, Armand; Lison, Hortensia; Cadranel, Jean-François; Degano, Bruno

    2016-05-01

    Hepatopulmonary syndrome (HPS) is defined by the association of portal hypertension, increased alveolar-arterial oxygen gradient and intrapulmonary vascular dilations. Pathophysiological mechanisms of hypoxemia are characterized by ventilation-perfusion mismatch, oxygen diffusion limitation between alveolus and the centre of the dilated capillary, and right-to-left shunting. An excess of vasodilator molecules (like nitric monoxide) and proangiogenic factors (like VEGF) play an important role in the occurrence of HPS. Symptoms of HPS are not specific and dominated by a progressive dyspnea in upright position. Pulse oximetry is a simple non-invasive screening test but only detect the most severe forms of HPS. Medical treatment is disappointing and only liver transplantation may lead to resolution of HPS. Survival following liver transplantation is promising when hypoxemia is not severely decreased. PMID:27021476

  10. Antiphospholipid syndrome.

    Science.gov (United States)

    George, Diane; Erkan, Doruk

    2009-01-01

    The antiphospholipid syndrome (APS) is an autoimmune systemic disease that is diagnosed when there is vascular thrombosis and/or pregnancy morbidity occurring with persistently positive antiphospholipid antibodies (aPL) (lupus anticoagulant test, anticardiolipin antibodies, and/or anti-beta(2)-glycoprotein I antibodies). Although International APS Classification Criteria have been formulated to provide a uniform approach to APS research, aPL may cause a spectrum of clinical manifestations, some of which are not included in these criteria. The main aPL-related cardiac manifestations include valve abnormalities (vegetations and/or thickening), myocardial infarction (MI), intracardiac thrombi, and myocardial microthrombosis. In this article, we will review the definition, etiopathogenesis, clinical manifestations, diagnosis, and treatment of aPL-related clinical events with emphasis on cardiac manifestations. PMID:19732604

  11. Noonan syndrome

    Directory of Open Access Journals (Sweden)

    van der Burgt Ineke

    2007-01-01

    Full Text Available Abstract Noonan Syndrome (NS is characterised by short stature, typical facial dysmorphology and congenital heart defects. The incidence of NS is estimated to be between 1:1000 and 1:2500 live births. The main facial features of NS are hypertelorism with down-slanting palpebral fissures, ptosis and low-set posteriorly rotated ears with a thickened helix. The cardiovascular defects most commonly associated with this condition are pulmonary stenosis and hypertrophic cardiomyopathy. Other associated features are webbed neck, chest deformity, mild intellectual deficit, cryptorchidism, poor feeding in infancy, bleeding tendency and lymphatic dysplasias. The syndrome is transmitted as an autosomal dominant trait. In approximately 50% of cases, the disease is caused by missense mutations in the PTPN11 gene on chromosome 12, resulting in a gain of function of the non-receptor protein tyrosine phosphatase SHP-2 protein. Recently, mutations in the KRAS gene have been identified in a small proportion of patients with NS. A DNA test for mutation analysis can be carried out on blood, chorionic villi and amniotic fluid samples. NS should be considered in all foetuses with polyhydramnion, pleural effusions, oedema and increased nuchal fluid with a normal karyotype. With special care and counselling, the majority of children with NS will grow up and function normally in the adult world. Management should address feeding problems in early childhood, evaluation of cardiac function and assessment of growth and motor development. Physiotherapy and/or speech therapy should be offered if indicated. A complete eye examination and hearing evaluation should be performed during the first few years of schooling. Preoperative coagulation studies are indicated. Signs and symptoms lessen with age and most adults with NS do not require special medical care.

  12. Griscelli Syndrome: A Case Report

    Directory of Open Access Journals (Sweden)

    Seyed Ebrahim MANSOURI NEJAD

    2014-12-01

    Full Text Available How to Cite This Article: Mansouri Nejad SE, Yazdan panah MJ, Tayyebi Meibodi N, Ashrafzadeh F, Akhondian J, BeiraghiToosi M, Eslamieh H. Griscelli Syndrome: A Case Report. Iran J Child Neurol. 2014 Autumn;8(4: 72-75.ObjectiveGriscelli syndrome (GS is a rare autosomal recessive immune deficiency disorder that presents with pigmentary dilution of the skin and hair, recurrent skin and pulmonary infections, neurologic problems, hypogammaglobulinemia, and variable cellular immunodeficiency. Three mutations have been described in different phenotypes of the disease. In most of cases, GS leads to death in the first decade of life. In this article, we report a one-year-old child with type 2 GS who suffers from pigmentation disorder and hypogammaglobulinemia.ReferencesKharkar V, Pande S, Mahajan S, Dwiwedi R, Khopkar U. Griscelli syndrome: a new phenotype with circumscribed pigment loss? Dermatol Online J 2007 1;13(2:17.Sheela SR, Latha M, Susy JI. Griscelli syndrome: Rab 27a mutation. Indian Pediatrics 2004; 41:944-947.González Carretero P, Noguera Julian A, Ricart Campos S, Fortuny Guasch C, Martorell Sampol L. Griscelli-Prunieras syndrome: report of two cases. An Pediatr (Barc 2009 ; 70(2:164-7.Szczawinska-Poplonyk A, Kycler Z, Breborowicz A, Klaudel-Dreszler M, Pac M, Zegadlo-Mylik M, et al. Pulmonary lymphomatoid granulomatosis in Griscelli syndrome type 2. Viral Immunol 2011 Dec;24(6:471-3.Durmaz A, Ozkinay F, Onay H, Tombuloglu M, Atay A, Gursel O, et al. Molecular analysis and clinical findings of Griscelli syndrome patients. J Pediatr Hematol Oncol 2012 Oct;34(7:541-4.Reddy RR, Babu BM, Venkateshwaramma B, Hymavathi Ch. Silvery hair syndrome in two cousins: Chediak-Higashi syndrome vs Griscelli syndrome, with rare associations. Int J Trichology 2011; 3(2:107-11.Sahana M, Sacchidanand S, Hiremagalore R, Asha G. Silvery grey hair: clue to diagnose immunodeficiency. Int J Trichology 2012;4(2:83-5.Mahalingashetti PB, Krishnappa MH, Kalyan PS

  13. Prenatal Tests for Down Syndrome

    Science.gov (United States)

    PRENATAL TESTS FOR DOWN SYNDROME S HARE W ITH W OMEN PRENATAL TESTS FOR DOWN SYNDROME What Is Down Syndrome? ... suggests that you consult your health care provider. PRENATAL TESTS FOR DOWN SYNDROME 256 Volume 50, No. ...

  14. Genetics Home Reference: Rett syndrome

    Science.gov (United States)

    ... Help Me Understand Genetics Home Health Conditions Rett syndrome Rett syndrome Enable Javascript to view the expand/collapse ... autism-dementia-ataxia-loss of purposeful hand use syndrome Rett disorder Rett's disorder Rett's syndrome RTS RTT Related ...

  15. Gilles de la Tourette syndrome

    Science.gov (United States)

    ... cannot control. The condition is commonly called Tourette syndrome. ... Tourette syndrome ... fewer people have more severe forms of Tourette syndrome. Tourette syndrome is four times as likely to occur ...

  16. Nevoid Basal Cell Carcinoma Syndrome

    Science.gov (United States)

    ... Nevoid Basal Cell Carcinoma Syndrome Request Permissions Nevoid Basal Cell Carcinoma Syndrome Approved by the Cancer.Net Editorial Board , 04/2016 What is Nevoid Basal Cell Carcinoma Syndrome? Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is ...

  17. Research on Molecular Mechanism of “Yin Asthenia with Internal Heat” in Asthenia Hot Syndrome Rats by Gene Chip Technology%基因芯片技术研究虚热证大鼠阴虚内热的分子机制

    Institute of Scientific and Technical Information of China (English)

    韩冰冰; 王世军

    2013-01-01

    目的:通过基因芯片技术研究虚热证大鼠肝全基因表达谱的改变,阐释虚热证大鼠“阴虚内热”的分子机制.方法:使用中药复方附子、肉桂、干姜建立虚热证大鼠模型,应用基因芯片检测各组大鼠肝脏基因表达,筛选差异表达基因,进行基因功能分类注释,荧光定量PCR验证芯片结果.结果:虚热模型组与空白对照组比较有99条基因差异表达,主要涉及防御应答,固醇代谢等功能.结论:虚热证阴虚内热的分子机制可能与刺激应答相关基因及固醇代谢相关基因两类基因的异常表达相关.%To explain molecular mechanism of “Yin Asthenia with Internal Heat” in asthenia hot syndrome rats by analysis the whole gene expression profile of the hver in rats with asthenia hot syndrome.Methods:The Asthenia hot syndrome rats models were induced by compound preparation of Traditional Chinese Medicine of Aconitum carmichaeli,Cinnamomi Cortex,Rhizoma Zingiberis.The liver gene expression in each group was detected by gene chip.We selected the differential expression genes and conducted the significant analysis on the genetic function of differential genes.A part of genes were selected to test the accuracy of results by RT-PCR.Results:As compared to the control group,in asthenia hot model group there were 99 strips of differential expression gene,mainly about function of defense response and sterol metabolic process.Conclusion:The abnormal expression of genes about defense response and sterol metabolic process in asthenia hot syndrome rats is possibly related to the substance foundation of asthenia hot syndrome.

  18. Burning Mouth Syndrome and "Burning Mouth Syndrome".

    Science.gov (United States)

    Rifkind, Jacob Bernard

    2016-03-01

    Burning mouth syndrome is distressing to both the patient and practitioner unable to determine the cause of the patient's symptoms. Burning mouth syndrome is a diagnosis of exclusion, which is used only after nutritional deficiencies, mucosal disease, fungal infections, hormonal disturbances and contact stomatitis have been ruled out. This article will explore the many causes and treatment of patients who present with a chief complaint of "my mouth burns," including symptomatic treatment for those with burning mouth syndrome. PMID:27209717

  19. Mobbing syndrome

    Directory of Open Access Journals (Sweden)

    Sakoula Z.

    2014-07-01

    Full Text Available Introduction: The term mobbing comes from the English word mob, meaning attack, Compass bother. Today is the systematic psychological attack and a strategic marginalization accepted at the workplace from their superiors or colleagues unwanted, for various reasons, employees. The term was used in 1800 by British biology, description of aggressive behavior in flight, certain species of migratory birds. In 1900, ethologist Konrad Lorenz uses it to interpret the hostility of the majority of the herd, compared to lean animals of the same breed. The German psychologist Heinz Leyman, is the first, which is in the 80s, attributes the condition in human society, describing all the negative health effects of mobbing in the workplace as a "syndrome mobbing». Purpose: To work is to illustrate the phenomenon mobbing, which can appear as a problem in the relationship of the perpetrator to the victim, but also implies the presence of such conditions to occur and flourish. Literature Review: searched the literature, internet, Keyword: Work or Employee Abuse, Mistreatment, Emotional Abuse, Bossing, Victimization, Intimidation, Psychological terrorization, Psychological violence. The mobbing syndrome is defined as "repeated abusive behavior, manifested through actions, words, intimidation, acts, gestures, ways of organizing work and have the character or purpose to offend the personality, dignity or physical or mental integrity of the worker in the performance of his work, to jeopardize the employment status or to create a hostile, intimidating, degrading, humiliating or offensive working environment. According to the French psychiatrist Marie France Hirigoyen, the "offender" is a personality that satisfied 'hurting' his fellows and develops self-esteem, conveying to others the "pain" that cannot feel, but also the internal contradictions that refuses edited. Conclusions: the mobbing is the reason for the development of mental and physical diseases as an

  20. Hepatorenal Syndrome

    Directory of Open Access Journals (Sweden)

    Pınar Zeyneloğlu

    2012-04-01

    Full Text Available Renal failure is a common major complication in patients with advanced cirrhosis and generally indicates a poor prognosis when combined with liver failure. Hepatorenal syndrome (HRS is characterised by a combination of disturbances in circulatory and kidney function. Arterial pressure is decreased in the systemic circulation due to reduced total systemic vascular resistance. Kidney dysfunction is caused by reduction in renal blood flow. The diagnosis of HRS is based on exclusion of other disorders that cause acute kidney injury in cirrhosis as there are no specific tests. There are two types of HRS with different characteristics and prognostics. Liver transplantation is the treatment of choice for all patients without contraindication. The best approach to the pharmacologic management is the administration vasoconstrictor drugs based on the pathogenesis. Many vasoconstrictors including vasopressin analogues (terlipressin, ornipressin and vasopressin, somatostatin analogues (octreotide and alpha-adrenergic analogues (midodrine and norepinephrine have been studied. In most of the studies intravenous albumin therapy was coadministered with vasoconstrictor drugs and suggested that albumin should be considered as the component of pharmacologic intervention in patients with HRS. Renal replacement therapy in the form of hemodialysis or continuous venovenous hemofiltration has been used in the management of HRS patients awaiting transplantation or in those with acute potentially reversible conditions. The artificial hepatic support systems require further investigation. (Journal of the Turkish Society Intensive Care 2012; 10: 37-44

  1. Tourette syndrome.

    Science.gov (United States)

    Cavanna, Andrea E; Termine, Cristiano

    2012-01-01

    Tourette syndrome (TS) is a neurodevelopmental disorder consisting of multiple motor and one or more vocal/phonic tics. TS is increasingly recognized as a common neuropsychiatric disorder usually diagnosed in early childhood and comorbid neuropsychiatric disorders occur in approximately 90% of patients, with attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) being the most common ones. Moreover, a high prevalence of depression and personality disorders has been reported. Although the mainstream of tic management is represented by pharmacotherapy, different kinds of psychotherapy, along with neurosurgical interventions (especially deep brain stimulation, DBS) play a major role in the treatment of TS. The current diagnostic systems have dictated that TS is a unitary condition. However, recent studies have demonstrated that there may be more than one TS phenotype. In conclusion, it appears that TS probably should no longer be considered merely a motor disorder and, most importantly, that TS is no longer a unitary condition, as it was previously thought. PMID:22411257

  2. Leigh syndrome

    International Nuclear Information System (INIS)

    A male infant developed hypotonia at 5 months, vomiting, diarrhea, fever, generalized clonic convulsion, tonic spasm and periodical opisthotonus at 8 months, swallowing difficulty at 10 months, pes equinovarus and optic atrophy at 11 months, and then tachypnea, and died at 14 months of age. Parents were consanguinous. Laboratory studies revealed elevated serum LDH, CPK, lactate and Pyruvate. TPP-ATP phosphoryl transferase inhibitor was negative in urine. EEG showed irregular and diffuse slow waves and periodic diffuse spike and waves. CT scan at 9 months of age showed slightly low attenuation areas in the putamen bilaterally. At 11 months, a diffuse cerebral atrophy was found, and the low attenuation of the basal ganglia became more definite. No enhanced lesion was seen at 13 months of age. Thiamine tetra-hydrofurfuryl disulfide and lipoic acid were tried without success. The pathological findings of the brain were astrogliosis and proliferation of capillaries in putamen, thalamus, caudate neucleus, substantia nigra, pontine brachium and cerebral cortex, which were symmetrically involved. The symmetrical cavitation was found in putamen. Optic nerve and mamillary body were spared. CT scan findings corresponded well with the pathology of the necrotic lesions of the brain. It was concluded that these CT scan pictures described above may be diagnostic of Leigh syndrome. (author)

  3. Molecular and cellular analysis of the DNA repair defect in a patient in xeroderma pigmentosum complementation group D who has the clinical features of xeroderma pigmentosum and Cockayne syndrome.

    OpenAIRE

    Broughton, B.C.; Thompson, A F; Harcourt, S A; Vermeulen, Wim; Hoeijmakers, Jan; Botta, Elena; Stefanini, Miria; King, M.D.; Weber, Christine; Cole, J.; Arlett, C F; Lehmann, Alan

    1995-01-01

    textabstractXeroderma pigmentosum (XP) and Cockayne syndrome (CS) are quite distinct genetic disorders that are associated with defects in excision repair of UV-induced DNA damage. A few patients have been described previously with the clinical features of both disorders. In this paper we describe an individual in this category who has unusual cellular responses to UV light. We show that his cultured fibroblasts and lymphocytes are extremely sensitive to irradiation with UV-C, despite a level...

  4. Myelodysplastic syndromes.

    Science.gov (United States)

    Koeffler, H P

    1996-04-01

    These two issues of the Seminars in Hematology will provide the physician the necessary knowledge to help make sense of this somewhat confusing array of diseases. The subdivisions of MDS reflect the precision of our techniques of dissection, with morphological and histochemical analyses forming the foundation to identify and subdivide MDS. Although steady refinement has occurred over the last half-century, the basic morphologic technique is unchanged. Cytogenetic analysis, which has been possible since the 1960s and 1970s, should be done at least at initial presentation in all patients to provide refinement of diagnosis and prognosis. FISH is not, at this time, useful as a screening technique. Although the 1990s is an era of rapidly growing knowledge and technical abilities in molecular biology, the use of these techniques in MDS is in its infancy. Very few genes have been identified which are altered in MDS, although many must exist. The molecular assays continue to be cumbersome and impractical to use in the clinical laboratory and remain the domain of the research scientist. Nevertheless, in the future, molecular biology will enable the internist to give each individual a clearer diagnosis and prognosis and may even provide targetted therapies of patients with MDS. At this time the center of management is good supportive care. Some patients, however, will benefit from special interventions, which include the use of growth factors, BMT, and in selected patients, aggressive chemotherapy. Induction of differentiation of the abnormal hematopoietic clone remains only a dream, although some of the differentiation agents may have applicability for their ability to induce apoptosis and prevent growth of the MDS clone of cells. Many of the major advances in our knowledge of cancer developed through the study of hematopoietic malignancy. A lot of these advances are due to the ease of obtaining the abnormal cells. MDS provides an excellent model for studying the

  5. Targeted therapy for hereditary cancer syndromes: neurofibromatosis type 1, neurofibromatosis type 2, and Gorlin syndrome.

    Science.gov (United States)

    Agarwal, Rishi; Liebe, Sarah; Turski, Michelle L; Vidwans, Smruti J; Janku, Filip; Garrido-Laguna, Ignacio; Munoz, Javier; Schwab, Richard; Rodon, Jordi; Kurzrock, Razelle; Subbiah, Vivek

    2014-12-01

    Hereditary cancer syndromes are well known in the oncology community, typically affecting children, adolescents, and young adults and thereby resulting in great cumulative morbidity and mortality. These syndromes often lag behind their de novo counterparts in the development of approved novel treatment options due to their rarity in the general population. Recent work has allowed the identification of molecular aberrations and associated targeted therapies that may effectively treat these conditions. In this review, we seek to characterize some of the involved aberrations and associated targeted therapies for several germline malignancies, including neurofibromatosis types 1 and 2, and Gorlin syndrome. Though patients with hereditary cancer syndromes may be too rare to effectively include in large clinical trials, by understanding the pathophysiology of these diseases, clinicians can attain insights into the use of targeted therapies in their own practice when treating affected individuals. PMID:25549703

  6. Milk-alkali syndrome

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000332.htm Milk-alkali syndrome To use the sharing features on this page, please enable JavaScript. Milk-alkali syndrome is a condition in which there ...

  7. Androgen insensitivity syndrome

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001180.htm Androgen insensitivity syndrome To use the sharing features on this page, please enable JavaScript. Androgen insensitivity syndrome (AIS) is when a person who ...

  8. Diabetic hyperglycemic hyperosmolar syndrome

    Science.gov (United States)

    Diabetic hyperglycemic hyperosmolar syndrome (HHS) is a complication of type 2 diabetes . It involves extremely high blood ... Diabetic hyperglycemic hyperosmolar syndrome is a condition of: Extremely high blood sugar (glucose) level Extreme lack of ...

  9. Chinese restaurant syndrome

    Science.gov (United States)

    Chinese restaurant syndrome is a set of symptoms that some people have after eating Chinese food. A food additive ... Chinese restaurant syndrome is most often diagnosed based on the symptoms. The health care provider may ask the following ...

  10. International Rett Syndrome Foundation

    Science.gov (United States)

    ... Website What’s in Your State? For Families: Find Rett syndrome related resources in your state! State Resources Rettsyndrome.org is the world's leading Rett syndrome research funding organization We have invested $38 million ...

  11. What Causes Rett Syndrome?

    Science.gov (United States)

    ... Information Clinical Trials Resources and Publications What causes Rett syndrome? Skip sharing on social media links Share this: ... as bad for development as too little. Is Rett syndrome passed from one generation to the next? In ...

  12. What Is Marfan Syndrome?

    Science.gov (United States)

    ... 11:11 Size: 10.5 MB November 2014 What Is Marfan Syndrome? Fast Facts: An Easy-to- ... Being Done on Marfan Syndrome? For More Information What Is Connective Tissue? Connective tissue supports many parts ...

  13. Moebius Syndrome Foundation

    Science.gov (United States)

    ... FRAME video on Moebius syndrome The Moebius Syndrome Foundation is excited to announce the premiere of the FRAME video, produced by Rick Guidotti and his non-profit organization, Positive Exposure! FRAME is a web-based ...

  14. Diabetic hyperglycemic hyperosmolar syndrome

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000304.htm Diabetic hyperglycemic hyperosmolar syndrome To use the sharing features on this page, please enable JavaScript. Diabetic hyperglycemic hyperosmolar syndrome (HHS) is a complication of ...

  15. Green Nail Syndrome

    Science.gov (United States)

    ... Favorite Name: Category: Share: Yes No, Keep Private Green Nail Syndrome Share | Green nail syndrome (GNS) is an infection of the ... discoloration of nails, also known as chloronychia. The green discoloration varies from blue-green to dark green ...

  16. Sick sinus syndrome

    Science.gov (United States)

    ... chambers is a common cause of sick sinus syndrome. Coronary artery disease , high blood pressure, and aortic and ... pressure may be normal or low. Sick sinus syndrome may cause symptoms of heart failure to start or get worse. Sick sinus ...

  17. Carpal tunnel syndrome

    Science.gov (United States)

    Median nerve dysfunction; Median nerve entrapment ... Calandruccio JH. Carpal tunnel syndrome, ulnar tunnel syndrome, and stenosing tenosynovitis. In: Canale ST, Beaty JH, eds. Campbell's Operative Orthopaedics . 12th ed. Philadelphia, PA: Elsevier Mosby; 2013: ...

  18. Obesity hypoventilation syndrome (OHS)

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000085.htm Obesity hypoventilation syndrome (OHS) To use the sharing features on this page, please enable JavaScript. Obesity hypoventilation syndrome (OHS) is a condition in some ...

  19. Abdominal Pain Syndrome

    Science.gov (United States)

    ... inspection of a drop of urine), and urine culture for bacterial infection. Stools can be analyzed for ... Hepatitis C Inflammatory Bowel Disease Irritable Bowel Syndrome Obesity Digestive Health Topics Abdominal Pain Syndrome Belching, Bloating, ...

  20. Ovarian hyperstimulation syndrome

    Science.gov (United States)

    Ovarian hyperstimulation syndrome (OHSS) is a problem that is sometimes seen in women who take fertility medicines ... the belly and chest area. This is called ovarian hyperstimulation syndrome (OHSS). OHSS occurs only after the ...

  1. What is Down Syndrome?

    Science.gov (United States)

    ... Syndrome/Down-Syndrome-Facts/ [top] What are common symptoms? » ​​ Last Reviewed: 01/17/2014 Related A-Z Topics Autism Spectrum Disorder (ASD) Early Learning Intellectual and Developmental Disabilities (IDDs) All related ...

  2. Rubinstein-Taybi syndrome

    Science.gov (United States)

    Rubinstein syndrome, RTS ... Rubinstein-Taybi Parents Group USA: www.rubinstein-taybi.org ... Philadelphia, PA: Elsevier; 2016:chap 14. Stevens CA. Rubinstein-Taybi syndrome. Gene Reviews. 2014;8. PMID: 20301699 ...

  3. Munchausen syndrome by proxy

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001555.htm Munchausen syndrome by proxy To use the sharing features on this page, please enable JavaScript. Munchausen syndrome by proxy is a mental illness and a form of ...

  4. Learning about Klinefelter Syndrome

    Science.gov (United States)

    ... for the genetic terms used on this page Learning About Klinefelter Syndrome What is Klinefelter syndrome? What ... they are referred to a doctor to evaluate learning disabilities. The diagnosis may also be considered in ...

  5. Antiphospholipid Antibody Syndrome

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Is Antiphospholipid Antibody Syndrome? Antiphospholipid (AN-te-fos-fo-LIP-id) antibody ... weeks or months. This condition is called catastrophic antiphospholipid syndrome (CAPS). People who have APS also are at ...

  6. Down Syndrome (For Kids)

    Science.gov (United States)

    ... Dictionary of Medical Words En Español What Other Kids Are Reading Movie: Digestive System Winter Sports: Sledding, ... people who have it. What's Life Like for Kids With Down Syndrome? Many kids with Down syndrome ...

  7. Down Syndrome: Education

    Science.gov (United States)

    ... Kit Financials Newsroom Shop NDSS Home » Resources » Education Education This section includes information about inclusion, elementary and ... and postsecondary options for students with Down syndrome. Education & Down Syndrome This section provides an overview and ...

  8. Hantavirus Pulmonary Syndrome (HPS)

    Science.gov (United States)

    ... this page: About CDC.gov . Hantavirus Share Compartir Hantavirus Pulmonary Syndrome (HPS) Severe HPS. Image courtesy D. ... the workers showed evidence of infection or illness. Hantavirus Pulmonary Syndrome (HPS) Topics Transmission Where HPS is ...

  9. Turner Syndrome (For Parents)

    Science.gov (United States)

    ... special blood test that looks at chromosomes — a karyotype — is used to diagnose Turner syndrome. Several physical ... and prompt him or her to order a karyotype. Results that indicate Turner syndrome show 45 chromosomes ...

  10. Metabolic Syndrome and Migraine

    OpenAIRE

    Sachdev, Amit; Marmura, Michael J.

    2012-01-01

    Migraine and metabolic syndrome are highly prevalent and costly conditions. The two conditions coexist, but it is unclear what relationship may exist between the two processes. Metabolic syndrome involves a number of findings, including insulin resistance, systemic hypertension, obesity, a proinflammatory state, and a prothrombotic state. Only one study addresses migraine in metabolic syndrome, finding significant differences in the presentation of metabolic syndrome in migraineurs. However, ...

  11. The wellness syndrome

    DEFF Research Database (Denmark)

    Mik-Meyer, Nanna

    2015-01-01

    Klumme. Wellness er blevet et syndrom, og dets symptomer er angst, selvbebrejdelser og skyldfølelse. Kommentar med udgangspunkt i: Carl Cederström & Andre Spicer, "The Wellness Syndrome" (Polity Books, 2015. 200 p.).......Klumme. Wellness er blevet et syndrom, og dets symptomer er angst, selvbebrejdelser og skyldfølelse. Kommentar med udgangspunkt i: Carl Cederström & Andre Spicer, "The Wellness Syndrome" (Polity Books, 2015. 200 p.)....

  12. 应用实时荧光定量PCR快速分子诊断唐氏综合征%Application of real-time fluorescence quantitative PCR to rapid molecular detection of Down's syndrome

    Institute of Scientific and Technical Information of China (English)

    黄以宁; 廖灿; 涂新枝; 杨昕; 易翠兴; 黎丽仙

    2005-01-01

    目的探讨一种快速、准确诊断唐氏综合征的方法.方法采用实时荧光定量PCR技术,对25例唐氏患者、50名正常人外周血标本,扩增21号及1号、19号染色体上的多态位点,定量分析比较正常组及唐氏患者组的4对△Ct值.结果唐氏患者组△Ct值明显低于正常组,两组比较差异有统计学意义(P<0.001).初步建立了临床应用的参考值范围,可以有效区分出唐氏样本和正常样本.结论应用实时荧光定量PCR技术可快速、准确诊断唐氏综合征,为唐氏综合征的快速产前诊断开辟了新的途径.%Objective To develop a rapid and reliable technique for the detection of Down's syndrome. Methods The peripheral blood samples were collected from twenty-five Down's syndrome patients and fifty normal individuals. Four polymorphic loci on chromosomes 21, 1, 19 were anplified by real-time fluorescence quantitative PCR, and then four pairs of △Ct values were analytically compared between the two groups. Results The △Ct values of Down's syndrome patients were significantly lower than those of normal individuals, and the reference ranges for clinical applica tion were primarily established. The difference between the two groups was highly significant ( P < 0.001 ), and the ref erence ranges between the two groups were not overlapped. Real-time quantitative PCR technique can effectively differentiates Down's syndrome samples from the normal fetuses; furthermore, the results were consistent with those of the karyotype analysis. Conclusion Real-time quantitative PCR is a fast and reliable method that may provide a new approach for rapid detection of Down's syndrome.

  13. PRES syndrome

    International Nuclear Information System (INIS)

    Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological entity characterized by headache, confusion, visual disturbances, seizures and posterior transient changes on neuroimaging. PRES has been described in several conditions including hypertensive encephalopathy, preeclampsia, eclampsia, infections, electrolyte imbalance, hypercalcaemia and use of several drugs. It occurs due to elevated blood pressure which exceeds the autoregulatory capacity of brain vasculature. The posterior circulation supplied by vertibro-basilar system has poor sympathetic innervation and, therefore, is frequently involved. The role of neuroimaging is to establish the initial diagnosis and to exclude other causes of neurological symptoms and signs. NCCT is sufficient to make the diagnosis in a proper clinical setting. MRI features are characteristic and has diagnostic and prognostic value. Diffusion weighted imaging (DWI) can differentiate this condition from ischemia/cytotoxic edema. Differential diagnosis of PRES includes PCA territory infarcts, venous thrombosis, demyelinating disorders, vasculitis and encephalitis. The diagnosis has important implications because the reversibility of the clinico-radiological abnormalities is contingent on the prompt control of blood pressure and/or withdrawing of the offending drug. We describe here a case of PRES in a 12 years old girl with acute lymphoblasts leukaemia, treated with cytostatics-vincristine, pharmorubycin and methotrexate. After 39 days from the beginning of the treatment there are good results in the myelogram and the flowcytometric examination, but the patient made two tonic-clonic seizures. CT and MRI were made and signs of leucoencephalopathy were diagnosed. Several control MRI examinations after cessation of the therapy and disappearance of the neurologic symptoms were made. The normal findings and the clinical course were the reasons for the PRES diagnosis

  14. Brugada syndrome

    Directory of Open Access Journals (Sweden)

    Priori Silvia G

    2006-09-01

    Full Text Available Abstract A novel clinical entity characterized by ST segment elevation in right precordial leads (V1 to V3, incomplete or complete right bundle branch block, and susceptibility to ventricular tachyarrhythmia and sudden cardiac death has been described by Brugada et al. in 1992. This disease is now frequently called "Brugada syndrome" (BrS. The prevalence of BrS in the general population is unknown. The suggested prevalence ranges from 5/1,000 (Caucasians to 14/1,000 (Japanese. Syncope, typically occurring at rest or during sleep (in individuals in their third or fourth decades of life is a common presentation of BrS. In some cases, tachycardia does not terminate spontaneously and it may degenerate into ventricular fibrillation and lead to sudden death. Both sporadic and familial cases have been reported and pedigree analysis suggests an autosomal dominant pattern of inheritance. In approximately 20% of the cases BrS is caused by mutations in the SCN5A gene on chromosome 3p21-23, encoding the cardiac sodium channel, a protein involved in the control of myocardial excitability. Since the use of the implantable cardioverter defibrillator (ICD is the only therapeutic option of proven efficacy for primary and secondary prophylaxis of cardiac arrest, the identification of high-risk subjects is one of the major goals in the clinical decision-making process. Quinidine may be regarded as an adjunctive therapy for patients at higher risk and may reduce the number of cases of ICD shock in patients with multiple recurrences.

  15. Nijmegen breakage syndrome (NBS

    Directory of Open Access Journals (Sweden)

    Chrzanowska Krystyna H

    2012-02-01

    Full Text Available Abstract Nijmegen breakage syndrome (NBS is a rare autosomal recessive syndrome of chromosomal instability mainly characterized by microcephaly at birth, combined immunodeficiency and predisposition to malignancies. Due to a founder mutation in the underlying NBN gene (c.657_661del5 the disease is encountered most frequently among Slavic populations. The principal clinical manifestations of the syndrome are: microcephaly, present at birth and progressive with age, dysmorphic facial features, mild growth retardation, mild-to-moderate intellectual disability, and, in females, hypergonadotropic hypogonadism. Combined cellular and humoral immunodeficiency with recurrent sinopulmonary infections, a strong predisposition to develop malignancies (predominantly of lymphoid origin and radiosensitivity are other integral manifestations of the syndrome. The NBN gene codes for nibrin which, as part of a DNA repair complex, plays a critical nuclear role wherever double-stranded DNA ends occur, either physiologically or as a result of mutagenic exposure. Laboratory findings include: (1 spontaneous chromosomal breakage in peripheral T lymphocytes with rearrangements preferentially involving chromosomes 7 and 14, (2 sensitivity to ionizing radiation or radiomimetics as demonstrated in vitro by cytogenetic methods or by colony survival assay, (3 radioresistant DNA synthesis, (4 biallelic hypomorphic mutations in the NBN gene, and (5 absence of full-length nibrin protein. Microcephaly and immunodeficiency are common to DNA ligase IV deficiency (LIG4 syndrome and severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation due to NHEJ1 deficiency (NHEJ1 syndrome. In fact, NBS was most commonly confused with Fanconi anaemia and LIG4 syndrome. Genetic counselling should inform parents of an affected child of the 25% risk for further children to be affected. Prenatal molecular genetic diagnosis is possible if disease

  16. The acute radiation syndrome

    International Nuclear Information System (INIS)

    Symptoms and signs from medical aspects resulting from whole body exposure, or in the main part, to ionizing radiation are described. The dose-response relationship is studied and the exposure is divided in three parts: central nervous system syndrome, gastrointestinal syndrome and hematopoietic syndrome. Brief comments about the treatment are reported. (M.A.C.)

  17. CONSTIPATION IN RETT SYNDROME

    Science.gov (United States)

    Gastrointestinal problems occur frequently in girls with Rett syndrome. Constipation is a common problem in girls with Rett syndrome because of their neurological abnormalities. Research studies to better understand the abnormalities of large bowel function in our girls with Rett syndrome have not b...

  18. What Is Usher Syndrome?

    Science.gov (United States)

    ... into electrical impulses that transfer messages to the brain. How is Usher syndrome inherited? Usher syndrome is ... required for the child to be affected. A person with only one copy of the gene is a ... in deafness and deaf-blindness, but are not related to Usher syndrome. ...

  19. Stiff skin syndrome.

    Science.gov (United States)

    Geng, S; Lei, X; Toyohara, J P; Zhan, P; Wang, J; Tan, S

    2006-07-01

    Stiff skin syndrome is a rare disorder characterized by pronounced skin induration, mild hypertrichosis and limited joint mobility, predominantly on the buttocks and thighs. Many heterogeneous cases have been reported under the name of stiff skin syndrome. We present a case of stiff skin syndrome from China, the diagnosis based on the patient's typical clinical and histopathological features. PMID:16836505

  20. Munchausen syndrome by proxy

    Science.gov (United States)

    Munchausen syndrome by proxy is a mental illness and a form of child abuse . The caretaker of ... No one is sure what causes Munchausen syndrome by proxy. Sometimes, the person was abused as a child or has Munchausen syndrome (fake illness for themselves).