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Sample records for autosomal recessive polycystic

  1. Caroli′s syndrome with autosomal recessive polycystic kidney disease

    OpenAIRE

    Prithi Shenoy; Syed Ahmed Zaki; Preeti Shanbag; Swapnil Bhongade

    2014-01-01

    Caroli′s syndrome (CS) is a rare congenital disorder characterized by multiple segmental cystic or saccular dilatations of the intrahepatic bile ducts and congenital hepatic fibrosis. We report a 9-year-old boy who was diagnosed with CS and autosomal recessive poly-cystic kidney disease. On screening, his 5-month-old asymptomatic sister had multiple dilated biliary radicals with multiple bilateral renal cystic lesions. Both the patient and the affected sibling have been advised regular follow...

  2. Autosomal recessive polycystic kidney disease. A case report.

    Directory of Open Access Journals (Sweden)

    Hernando Diocaretz V

    2015-01-01

    Full Text Available INTRODUCTION: Polycystic Kidney Disease is a genetic disorder characterized by progressive cystic dilations of the renal ducts, presenting as autosomal dominant or recessive forms with an incidence of 1 in 1.000 and 1 in 20.000 births, respectively, according to international series. The autosomal recessive variety can be lethal in the neonatal period due to respiratory failure secondary to pulmonary hypoplasia and can manifest during childhood with hypertension, short stature and complications of portal hypertension. CASE REPORT: 3 years and 11 months old preschoolar with antecedent of fetal growth restriction and oligohydramnios during prenatal period, and a history of asthenia, pallor and progressive feeding difficulty with postprandial vomiting. Physical examination shows cardiac bruit, hypertension, splenomegaly, caput medusae and short stature. Laboratory tests with peripheral pancytopenia; abdominal ultrasonography showed hepatosplenomegaly, findings consistent with autosomal recessive polycystic kidney disease and periportal fibrosis; renal scintigraphy with bilateral kidney failure; a positive fecal occult blood test; an upper endoscopy that shows small esophageal varices; a hand radiography that shows bone age delayed and an echocardiography with cardiomegaly. DISCUSSION: This infrequent disease requires a high degree of suspicion by the clinician and presents with portal hypertension, with platelet count being the best predictor of severity. This condition has no cure and will progress to end-stage renal disease in any moment, so the aim is to minimize and treat renal and hepatic complications.

  3. Caroli′s syndrome with autosomal recessive polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    Prithi Shenoy

    2014-01-01

    Full Text Available Caroli′s syndrome (CS is a rare congenital disorder characterized by multiple segmental cystic or saccular dilatations of the intrahepatic bile ducts and congenital hepatic fibrosis. We report a 9-year-old boy who was diagnosed with CS and autosomal recessive poly-cystic kidney disease. On screening, his 5-month-old asymptomatic sister had multiple dilated biliary radicals with multiple bilateral renal cystic lesions. Both the patient and the affected sibling have been advised regular follow-up for monitoring the progression of the disease. In conclusion, patients with CS should be screened for renal cystic lesions and vice versa even if they are asymptomatic. Also, as the disease is inherited in an autosomal recessive manner, it is important to screen family members for early diagnosis and management.

  4. Caroli's syndrome with autosomal recessive polycystic kidney disease.

    Science.gov (United States)

    Shenoy, Prithi; Zaki, Syed Ahmed; Shanbag, Preeti; Bhongade, Swapnil

    2014-07-01

    Caroli's syndrome (CS) is a rare congenital disorder characterized by multiple segmental cystic or saccular dilatations of the intrahepatic bile ducts and congenital hepatic fibrosis. We report a 9-year-old boy who was diagnosed with CS and autosomal recessive poly-cystic kidney disease. On screening, his 5-month-old asymptomatic sister had multiple dilated biliary radicals with multiple bilateral renal cystic lesions. Both the patient and the affected sibling have been advised regular follow-up for monitoring the progression of the disease. In conclusion, patients with CS should be screened for renal cystic lesions and vice versa even if they are asymptomatic. Also, as the disease is inherited in an autosomal recessive manner, it is important to screen family members for early diagnosis and management. PMID:24969198

  5. MR cholangiography in children with autosomal recessive polycystic kidney disease

    International Nuclear Information System (INIS)

    Background. Magnetic resonance cholangiography (MRC) is a relatively new, non-invasive imaging technique of the biliary tree that has shown good correlation with endoscopic retrograde cholangiopancreatography. The liver manifestation of autosomal recessive polycystic kidney disease (ARPKD) is congenital hepatic fibrosis (CHF). CHF may be accompanied by Caroli's disease, which is characterised by a non-obstructive dilation of the intrahepatic bile ducts. Objective. A prospective study was conducted to determine the presence and extent of Caroli's disease in children with ARPKD. Materials and methods. Seven children with ARPKD aged from 3.0 to 10.1 years were examined. CHF was confirmed in all biopsied cases (5 of 7). All children had been followed by repeated abdominal US examinations for many years. The MR examination included a morphological imaging study using a T2-weighted turbo spin-echo sequence and a heavily T2-weighted inversion-recovery turbo spin-echo sequence with three-dimensional maximum intensity projection (MIP) reconstructions for MRC. Results. The diagnosis of Caroli's disease could be made in one case by US; in two other children Caroli's disease was suspected, but the differentiation from hepatic cysts was not possible. By MRC, Caroli's disease could be diagnosed in three of seven children. Furthermore, MRC with MIP reconstructions demonstrated the extent of the disease by showing the entire biliary tree from different angles. Conclusions. MRC is a valuable method to establish the diagnosis and demonstrate the extent of Caroli's disease. (orig.)

  6. MR cholangiography in children with autosomal recessive polycystic kidney disease

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    Jung, G. [Department of Radiology, University of Cologne, Cologne (Germany)]|[Institut fuer Diagnostische Radiologie, Heinrich Heine Univ., Duesseldorf (Germany); Benz-Bohm, G.; Kugel, H. [Department of Radiology, University of Cologne, Cologne (Germany); Keller, K.M. [Department of Pediatrics, University of Bonn, Bonn (Germany); Querfeld, U. [Department of Pediatrics, University of Cologne, Cologne (Germany)

    1999-06-01

    Background. Magnetic resonance cholangiography (MRC) is a relatively new, non-invasive imaging technique of the biliary tree that has shown good correlation with endoscopic retrograde cholangiopancreatography. The liver manifestation of autosomal recessive polycystic kidney disease (ARPKD) is congenital hepatic fibrosis (CHF). CHF may be accompanied by Caroli`s disease, which is characterised by a non-obstructive dilation of the intrahepatic bile ducts. Objective. A prospective study was conducted to determine the presence and extent of Caroli`s disease in children with ARPKD. Materials and methods. Seven children with ARPKD aged from 3.0 to 10.1 years were examined. CHF was confirmed in all biopsied cases (5 of 7). All children had been followed by repeated abdominal US examinations for many years. The MR examination included a morphological imaging study using a T2-weighted turbo spin-echo sequence and a heavily T2-weighted inversion-recovery turbo spin-echo sequence with three-dimensional maximum intensity projection (MIP) reconstructions for MRC. Results. The diagnosis of Caroli`s disease could be made in one case by US; in two other children Caroli`s disease was suspected, but the differentiation from hepatic cysts was not possible. By MRC, Caroli`s disease could be diagnosed in three of seven children. Furthermore, MRC with MIP reconstructions demonstrated the extent of the disease by showing the entire biliary tree from different angles. Conclusions. MRC is a valuable method to establish the diagnosis and demonstrate the extent of Caroli`s disease. (orig.) With 1 fig., 1 tab., 18 refs.

  7. Prenatal diagnosis by ultrasound in pregnancies at risk for autosomal recessive polycystic kidney disease

    NARCIS (Netherlands)

    A. Reuss (Annette); J.W. Wladimiroff (Juriy); P.A. Stewart (Patricia); M.F. Niermeijer (Martinus)

    1990-01-01

    markdownabstractAbstract In 15 pregnancies at risk of the autosomal recessive type of polycystic kidney disease (ARPKD), there were six recurrences (40%), five of which were diagnosed prenatally between 17 and 26 weeks (mean, 22 weeks). In the remaining affected case, normal kidney size and echoge

  8. Caroli's Syndrome with Autosomal Recessive Polycystic Kidney Disease in a Two Month Old Infant

    OpenAIRE

    Kim, Jeong Tae; Hur, Yoon Jeong; Park, Jee Min; Kim, Myung Joon; Park, Young Nyun; Lee, Jae Seung

    2006-01-01

    Caroli's syndrome is a rare congenital disorder that involves intrahepatic bile duct ectasia and congenital hepatic fibrosis, frequently seen with concomitant autosomal recessive polycystic kidney disease (ARPKD). Literature on infants with ARPKD is rare. Here, we present a case of a two month old boy who was diagnosed with Caroli's syndrome and ARPKD.

  9. Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy.

    Directory of Open Access Journals (Sweden)

    K J Kelly

    Full Text Available Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA.

  10. TRPV4 Dysfunction Promotes Renal Cystogenesis in Autosomal Recessive Polycystic Kidney Disease

    OpenAIRE

    Zaika, Oleg; Mamenko, Mykola; Berrout, Jonathan; Boukelmoune, Nabila; O'Neil, Roger G.; Pochynyuk, Oleh

    2013-01-01

    The molecular mechanism of cyst formation and expansion in autosomal recessive polycystic kidney disease (ARPKD) is poorly understood, but impaired mechanosensitivity to tubular flow and dysfunctional calcium signaling are important contributors. The activity of the mechanosensitive Ca2+-permeable TRPV4 channel underlies flow-dependent Ca2+ signaling in murine collecting duct (CD) cells, suggesting that this channel may contribute to cystogenesis in ARPKD. Here, we developed a method to isola...

  11. Elevated c-myc protooncogene expression in autosomal recessive polycystic kidney disease

    International Nuclear Information System (INIS)

    The polycystic kidney diseases (PKDs) are a group of disorders characterized by the growth of epithelial cysts from the nephrons and collecting ducts of kidney tubules. The diseases can be inherited or can be provoked by environmental factors. To investigate the molecular basis of the abnormal cell growth associated with PKD, c-myc protooncogene expression was studied in a mouse model for autosomal recessive PKD. Homozygous recessive C57BL/6J (cpk/cpk) mice develop massively enlarged cystic kidneys and die from renal failure shortly after 3 weeks of age. Quantitative dot blot and RNA blot hybridization experiments in which whole kidney poly(A)+ RNA was hybridized with a c-myc RNA probe showed a 2- to 6-fold increase in c-myc mRNA at 2 weeks, and a 25- to 30-fold increase in c-myc mRNA at 3 weeks of age in polycystic mice, as compared to normal littermates. c-myc expression was also examined under two conditions in which kidney cell growth was experimentally induced in normal adult mice: compensatory renal hypertrophy and tubule regeneration following folic acid-induced renal cell injury. While compensatory hypertrophy resulted in only a small increase in c-myc, folic acid treatment gave rise after 24 hr to a 12-fold increase in c-myc RNA. The induction of c-myc by folic acid is consistent with increased cellular proliferation regenerating tubules. In contrast, polycystic kidneys show only a minimal increase in cellular proliferation over that seen in normal kidneys, while c-myc levels were found to be markedly elevated. Thus, the level of c-myc expression in cystic kidneys appears to be out of proportion to the rate of cell division, suggesting that elevated and potentially abnormal c-myc expression may be involved in the pathogenesis of PKD

  12. Next-generation sequencing for molecular diagnosis of autosomal recessive polycystic kidney disease.

    Science.gov (United States)

    Edrees, Burhan M; Athar, Mohammad; Al-Allaf, Faisal A; Taher, Mohiuddin M; Khan, Wajahatullah; Bouazzaoui, Abdellatif; Al-Harbi, Naffaa; Safar, Ramzia; Al-Edressi, Howaida; Alansary, Khawala; Anazi, Abulkareem; Altayeb, Naji; Ahmed, Muawia A; Abduljaleel, Zainularifeen

    2016-10-10

    Autosomal recessive polycystic kidney disease (ARPKD) a rare genetic disorder, described by formation of cysts in the kidney. A targeted customized sequencing of genes implicated in ARPKD phenotype was performed to identify candidate variants using the Ion torrent PGM next-generation sequencing. The results identified likely pathogenic disease causing variants during the validation process. Four potential pathogenic variants [c.4870C>T, p.(Arg1624Trp)], [c.5725C>T, p.(Arg1909Trp)], c.1736C>T, p.(Thr579Met)] and [(c.10628T>G), p.(Leu3543Trp)] were observed in PKHD1 gene among 12 out of 18 samples. The rest of the patient samples also showed few variants in ADPKD (Autosomal Dominant Polycystic Kidney Disease) disease causing genes PKD1 and PKD2 i.e. [c.12433G>A, p.(Val4145Ile)] and [c.1445T>G, p.(Phe482Cys)], respectively. All causative variants were validated by capillary sequencing, confirming the presence of a novel homozygous variants [c.10628T>G, p.(Leu3543Trp)] found in exon 61 of a male proband. All potentially deleterious variants identified in PKHD1, PKD1, and PKD2 gene, also exhibited pathologically or clinically significance based on the computational predictions involved in predicting the impact of non-synonymous SNPs (nsSNPs) on protein function such as Sorting Intolerant From Tolerant (SIFT) and Polymorphism Phenotyping (PolyPhen2). SIFT classified 50% of our nsSNPs as "deleterious", while PolyPhen2 identified 45% of our nsSNPs as "Probably damaged" and the results from both programs were largely complementary. Taken together, these results suggest that the NGS strategies provide a fast, accurate and cost-effective molecular diagnostic tool for identifying mutations in targeted genes sequence analysis. PMID:27401137

  13. CONSENSUS EXPERT RECOMMENDATIONS FOR THE DIAGNOSIS AND MANAGEMENT OF AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE: REPORT OF AN INTERNATIONAL CONFERENCE

    OpenAIRE

    Guay-Woodford, Lisa M.; Bissler, John J.; Braun, Michael C.; Bockenhauer, Detlef; Cadnapaphornchai, Melissa A.; Dell, Katherine M.; Kerecuk, Larissa; Liebau, Max C; Alonso-Peclet, Maria H.; Shneider, Benjamin; Emre, Sukru; Heller, Theo; Kamath, Binita M.; Murray, Karen F.; Moise, Kenneth

    2014-01-01

    Autosomal recessive polycystic kidney disease (ARPKD; MIM 263200) is a severe, typically early onset form of cystic disease that primarily involves the kidneys and biliary tract. Phenotypic expression and age at presentation can be quite variable1. The incidence of ARPKD is 1 in 20,000 live births2, and its pleotropic manifestations are potentially life-threatening. Optimal care requires proper surveillance to limit morbidity and mortality, knowledgeable approaches to diagnosis and treatment,...

  14. TRPV4 Dysfunction Promotes Renal Cystogenesis in Autosomal Recessive Polycystic Kidney Disease

    Science.gov (United States)

    Zaika, Oleg; Mamenko, Mykola; Berrout, Jonathan; Boukelmoune, Nabila; O'Neil, Roger G.

    2013-01-01

    The molecular mechanism of cyst formation and expansion in autosomal recessive polycystic kidney disease (ARPKD) is poorly understood, but impaired mechanosensitivity to tubular flow and dysfunctional calcium signaling are important contributors. The activity of the mechanosensitive Ca2+-permeable TRPV4 channel underlies flow-dependent Ca2+ signaling in murine collecting duct (CD) cells, suggesting that this channel may contribute to cystogenesis in ARPKD. Here, we developed a method to isolate CD-derived cysts and studied TRPV4 function in these cysts laid open as monolayers and in nondilated split-open CDs in a rat model of ARPKD. In freshly isolated CD-derived cyst monolayers, we observed markedly impaired TRPV4 activity, abnormal subcellular localization of the channel, disrupted TRPV4 glycosylation, decreased basal [Ca2+]i, and loss of flow-mediated [Ca2+]i signaling. In contrast, nondilated CDs of these rats exhibited functional TRPV4 with largely preserved mechanosensitive properties. Long-term systemic augmentation of TRPV4 activity with a selective TRPV4 activator significantly attenuated the renal manifestations of ARPKD in a time-dependent manner. At the cellular level, selective activation of TRPV4 restored mechanosensitive Ca2+ signaling as well as the function and subcellular distribution of TRPV4. In conclusion, the functional status of TRPV4, which underlies mechanosensitive Ca2+ signaling in CD cells, inversely correlates with renal cystogenesis in ARPKD. Augmenting TRPV4 activity may have therapeutic potential in ARPKD. PMID:23411787

  15. Telmisartan Ameliorates Fibrocystic Liver Disease in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease

    Science.gov (United States)

    Yoshihara, Daisuke; Kugita, Masanori; Sasaki, Mai; Horie, Shigeo; Nakanishi, Koichi; Abe, Takaaki; Aukema, Harold M.; Yamaguchi, Tamio; Nagao, Shizuko

    2013-01-01

    Human autosomal recessive polycystic kidney disease (ARPKD) produces kidneys which are massively enlarged due to multiple cysts, hypertension, and congenital hepatic fibrosis characterized by dilated bile ducts and portal hypertension. The PCK rat is an orthologous model of human ARPKD with numerous fluid-filled cysts caused by stimulated cellular proliferation in the renal tubules and hepatic bile duct epithelia, with interstitial fibrosis developed in the liver. We previously reported that a peroxisome proliferator activated receptor (PPAR)-γ full agonist ameliorated kidney and liver disease in PCK rats. Telmisartan is an angiotensin receptor blocker (ARB) used widely as an antihypertensive drug and shows partial PPAR-γ agonist activity. It also has nephroprotective activity in diabetes and renal injury and prevents the effects of drug-induced hepatotoxicity and hepatic fibrosis. In the present study, we determined whether telmisartan ameliorates progression of polycystic kidney and fibrocystic liver disease in PCK rats. Five male and 5 female PCK and normal control (+/+) rats were orally administered 3 mg/kg telmisartan or vehicle every day from 4 to 20 weeks of age. Treatment with telmisartan decreased blood pressure in both PCK and +/+ rats. Blood levels of aspartate amino transferase, alanine amino transferase and urea nitrogen were unaffected by telmisartan treatment. There was no effect on kidney disease progression, but liver weight relative to body weight, liver cystic area, hepatic fibrosis index, expression levels of Ki67 and TGF-β, and the number of Ki67- and TGF-β-positive interstitial cells in the liver were significantly decreased in telmisartan-treated PCK rats. Therefore, telmisartan ameliorates congenital hepatic fibrosis in ARPKD, possibly through the inhibition of signaling cascades responsible for cellular proliferation and interstitial fibrosis in PCK rats. The present results support the potential therapeutic use of ARBs for the

  16. CONSENSUS EXPERT RECOMMENDATIONS FOR THE DIAGNOSIS AND MANAGEMENT OF AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE: REPORT OF AN INTERNATIONAL CONFERENCE

    Science.gov (United States)

    Guay-Woodford, Lisa M.; Bissler, John J.; Braun, Michael C.; Bockenhauer, Detlef; Cadnapaphornchai, Melissa A.; Dell, Katherine M.; Kerecuk, Larissa; Liebau, Max C.; Alonso-Peclet, Maria H.; Shneider, Benjamin; Emre, Sukru; Heller, Theo; Kamath, Binita M.; Murray, Karen F.; Moise, Kenneth; Eichenwald, Eric E.; Evans, Jacquelyn; Keller, Roberta L.; Wilkins-Haug, Louise; Bergmann, Carsten; Gunay-Aygun, Meral; Hooper, Stephen R.; Hardy, Kristina K.; Hartung, Erum A.; Streisand, Randi; Perrone, Ronald; Moxey-Mims, Marva

    2015-01-01

    Autosomal recessive polycystic kidney disease (ARPKD; MIM 263200) is a severe, typically early onset form of cystic disease that primarily involves the kidneys and biliary tract. Phenotypic expression and age at presentation can be quite variable1. The incidence of ARPKD is 1 in 20,000 live births2, and its pleotropic manifestations are potentially life-threatening. Optimal care requires proper surveillance to limit morbidity and mortality, knowledgeable approaches to diagnosis and treatment, and informed strategies to optimize quality of life. Clinical management therefore is ideally directed by multidisciplinary care teams consisting of perinatologists, neonatologists, nephrologists, hepatologists, geneticists, and behavioral specialists to coordinate patient care from the perinatal period to adulthood. In May 2013, an international team of 25 multidisciplinary specialists from the US, Canada, Germany, and the United Kingdom convened in Washington, DC, to review the literature published from 1990 to 2013 and to develop recommendations for diagnosis, surveillance, and clinical management. Identification of the gene PKHD1, and the significant advances in perinatal care, imaging, medical management, and behavioral therapies over the past decade, provide the foundational elements to define diagnostic criteria and establish clinical management guidelines as the first steps towards standardizing the clinical care for ARPKD patients. The key issues discussed included recommendations regarding perinatal interventions, diagnostic criteria, genetic testing, management of renal and biliary-associated morbidities, and behavioral assessment. The meeting was funded by the National Institutes of Health and an educational grant from the Polycystic Kidney Disease Foundation. Here we summarize the discussions and provide an updated set of diagnostic, surveillance, and management recommendations for optimizing the pediatric care of patients with ARPKD. Specialist care of ARPKD

  17. The emergence of hepatic fibrosis and portal hypertension in infants and children with autosomal recessive polycystic kidney disease

    International Nuclear Information System (INIS)

    Long-term imaging and clinical findings are reported in six children whose polycystic kidney disease was detected in infancy or early childhood. Over time (2 years to 20 years) all patients developed portal hypertension from hepatic fibrosis, a problem primarily noted in recessive pattern polycystic kidney disease. Mild renal failure (two patients) was accompanied by serious systemic hypertension in the same patients. In one family, one of the babies also showed dilated right hepatic ducts. Imaging studies included urography and CT although recently ultrasonography was the method of choice. The relative renal and hepatic manifestations in these patients so changed with time that it would seem fallacious to attempt to use rigid classifications based on findings at initial diagnosis. (orig.)

  18. High Resolution Ultrasonography for Assessment of Renal Cysts in the PCK Rat Model of Autosomal Recessive Polycystic Kidney Disease

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    Sarika Kapoor

    2016-03-01

    Full Text Available Background/Aims: The PCK rat model of polycystic kidney disease is characterized by the progressive development of renal medullary cysts. Here, we evaluated the suitability of high resolution ultrasonography (HRU to assess the kidney and cyst volume in PCK rats, testing three different ultrasound image analysis methods, and correlating them with kidneys weights and histological examinations. Methods: After inducing anesthesia, PCK rats (n=18 were subjected to HRU to visualize the kidneys, to perform numeric and volumetric measurements of the kidney and any cysts observed, and to generate 3-dimensional images of the cysts within the kidney parenchyma. Results: HRU provided superior information in comparison to microscopic analysis of stained kidney sections. HRU-based kidney volumes correlated strongly with kidney weights (R2=0.809; PConclusion: HRU represents a useful diagnostic tool for kidney and cyst volume measurements in PCK rats. Sequential HRU examinations may be useful to study the effect of drugs on cyst growth without the need to euthanize experimental animals.

  19. MRI assessment of fetal autosomal recessive polycystic kidney disease%常染色体隐性遗传性多囊肾病胎儿的MRI表现

    Institute of Scientific and Technical Information of China (English)

    董素贞; 朱铭; 钟玉敏; 张弘; 潘慧红

    2014-01-01

    目的 探讨MRI对常染色体隐性遗传性多囊肾病(ARPKD)胎儿的诊断价值.方法 回顾性分析2005年7月至2013年12月间产前超声检查提示异常,然后行MR检查,并经引产后尸解或病理证实的ARPKD胎儿16例.MR扫描序列主要采用稳态自由进动(SSFP)序列、单次激发快速自旋回波(SSTSE)序列和快速加权序列T1WI.将产前MRI、超声表现与引产后尸解或病理结果进行对照分析.结果 16例ARPKD患儿均表现为双侧肾脏体积明显增大,SSTSE序列肾髓质弥漫性高信号小囊肿.11例合并羊水过少,11例合并双肺发育不良,6例合并肝纤维化.11例双肺发育不良和6例肝脏轻度纤维化超声均未提示,肾脏病变超声误诊1例,MRI诊断均正确.结论 MRI诊断胎儿ARPKD具有明显优势,不受羊水量的影响,能准确评价肾脏及肺异常.%Objective To explore the value of MRI on fetal autosomal recessive polycystic kidney disease (ARPKD).Methods Sixteen pregnant women,aged from 28 to 38 years (average 30 years) and with gestation age from 22 to 36 weeks (average 25 weeks) underwent MR scanning with a 1.5 T MR unit within 24 to 48 hours after ultrasound examinations.The imaging sequences included steady-state free-precession (SSFP) sequence,single-shot turbo spin echo (SSTSE) sequence and T1-weighted fast imaging sequence.Prenatal US and MR imaging findings were compared with autopsy or pathological results.Results A total of 16 cases of ARPKD showed bilateral markedly enlarged kidneys and diffuse high signal small cysts in renal medulla on SSTSE sequence.Among the 16 cases,11 cases were with oligohydramnios,1 1 cases were with pulmonary hypoplasia,and 6 cases were with hepatic fibrosis.Eleven cases of pulmonary hypoplasia and 6 cases of hepatic fibrosis were all missed by US.For the diagnosis of the renal anomalies,US missed one case.MRI diagnosis was correct in all these cases.Conclusions MRI shows great advantages on the diagnosis of fetal ARPKD

  20. Genetics Home Reference: autosomal recessive hypotrichosis

    Science.gov (United States)

    ... Autosomal recessive hypotrichosis is a condition that affects hair growth. People with this condition have sparse hair ( hypotrichosis ) ... erosions) on the scalp. In areas of poor hair growth, they may also develop bumps called hyperkeratotic follicular ...

  1. Autosomal recessive osteopetrosis in Arab children.

    Science.gov (United States)

    Abdel-Al, Y K; Shabani, I S; Lubani, M M; al-Ghawabi, M A; Ibrahim, M D; al-Mohtaseb, S; Duodin, K I

    1994-01-01

    Nineteen Arab children including six boys and 13 girls in ten sibships were diagnosed as having osteopetrosis over a 5-year period in various hospitals in Kuwait. Eighteen patients had an isolated autosomal recessive form and one had autosomal recessive osteopetrosis associated with renal tubular acidosis. The mean age of diagnosis was 24 months. Parental consanguinity was high amongst them (68%). Anaemia, hepatosplenomegaly, failure to thrive, recurrent infections and neurological manifestations were common. Associated congenital abnormalities were found in 26%. Deafness, hydrocephalus and dental caries were relatively less common. A high mortality (37%) owing to infection was noted. The medical management and recommendations for patient care are discussed briefly. PMID:7516136

  2. Autosomal recessive diseases among Palestinian Arabs.

    OpenAIRE

    Zlotogora, J

    1997-01-01

    As a consequence of the high consanguinity rate among the Palestinian Arabs, many recessive disorders are present with a relatively high frequency. In a survey of 2000 different Palestinian Arab families who visited our genetic clinic, in 601 an autosomal recessive disease was diagnosed or strongly suspected. The distribution of these disorders was not uniform and some disorders, such as Krabbe disease, were found at high frequency in only a small part of the population. For some other disord...

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

    Directory of Open Access Journals (Sweden)

    Anup Hazra

    2014-01-01

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

  4. Genetics Home Reference: autosomal recessive cerebellar ataxia type 1

    Science.gov (United States)

    ... Genetics Home Health Conditions ARCA1 autosomal recessive cerebellar ataxia type 1 Enable Javascript to view the expand/ ... Open All Close All Description Autosomal recessive cerebellar ataxia type 1 ( ARCA1 ) is a condition characterized by ...

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

    OpenAIRE

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

    2009-01-01

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

  6. Global Gene Expression Profiling in PPAR-γ Agonist-Treated Kidneys in an Orthologous Rat Model of Human Autosomal Recessive Polycystic Kidney Disease

    Science.gov (United States)

    Yoshihara, Daisuke; Kugita, Masanori; Yamaguchi, Tamio; Aukema, Harold M.; Kurahashi, Hiroki; Morita, Miwa; Hiki, Yoshiyuki; Calvet, James P.; Wallace, Darren P.; Toyohara, Takafumi; Abe, Takaaki; Nagao, Shizuko

    2012-01-01

    Kidneys are enlarged by aberrant proliferation of tubule epithelial cells leading to the formation of numerous cysts, nephron loss, and interstitial fibrosis in polycystic kidney disease (PKD). Pioglitazone (PIO), a PPAR-γ agonist, decreased cell proliferation, interstitial fibrosis, and inflammation, and ameliorated PKD progression in PCK rats (Am. J. Physiol.-Renal, 2011). To explore genetic mechanisms involved, changes in global gene expression were analyzed. By Gene Set Enrichment Analysis of 30655 genes, 13 of the top 20 downregulated gene ontology biological process gene sets and six of the top 20 curated gene set canonical pathways identified to be downregulated by PIOtreatment were related to cell cycle and proliferation, including EGF, PDGF and JNK pathways. Their relevant pathways were identified using the Kyoto Encyclopedia of Gene and Genomes database. Stearoyl-coenzyme A desaturase 1 is a key enzyme in fatty acid metabolism found in the top 5 genes downregulated by PIO treatment. Immunohistochemical analysis revealed that the gene product of this enzyme was highly expressed in PCK kidneys and decreased by PIO. These data show that PIO alters the expression of genes involved in cell cycle progression, cell proliferation, and fatty acid metabolism. PMID:22666229

  7. Spectrum of Autosomal Recessive Congenital Ichthyosis in Scandinavia

    DEFF Research Database (Denmark)

    Hellström Pigg, Maritta; Bygum, Anette; Gånemo, Agneta; Virtanen, Marie; Brandrup, Flemming; Zimmer, Andreas D; Hotz, Alrun; Vahlquist, Anders; Fischer, Judith

    2016-01-01

    Autosomal recessive congenital ichthyosis (ARCI) represents a heterogeneous group of rare disorders of cornification with 3 major subtypes: harlequin ichthyosis (HI), lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE). A 4th subtype has also been proposed: pleomorphic...

  8. Urine proteome of autosomal dominant polycystic kidney disease patients

    OpenAIRE

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

    2012-01-01

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

  9. Tolvaptan in patients with autosomal dominant polycystic kidney disease

    OpenAIRE

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

    2012-01-01

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

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

    OpenAIRE

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

    2010-01-01

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

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

    OpenAIRE

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

    2013-01-01

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

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

    OpenAIRE

    Imed Helal

    2013-01-01

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

  13. Genetics Home Reference: autosomal recessive congenital methemoglobinemia

    Science.gov (United States)

    ... In type II, growth is often slowed. Abnormal facial muscle movements can interfere with swallowing, which can lead ... recessive congenital methemoglobinemia type I typically reduce enzyme activity or stability. As a result, the enzyme cannot ...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    OpenAIRE

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

    1998-01-01

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

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

    Science.gov (United States)

    Somlo, S; Markowitz, G S

    2000-07-01

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

  17. Nutraceutical for Autosomal Dominant Polycystic Kidney Disease Therapy.

    Science.gov (United States)

    Yuajit, Chaowalit; Chatsudthipong, Varanuj

    2016-01-01

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

  18. Genetics Home Reference: autosomal recessive spastic ataxia of Charlevoix-Saguenay

    Science.gov (United States)

    ... Genetics Home Health Conditions ARSACS autosomal recessive spastic ataxia of Charlevoix-Saguenay Enable Javascript to view the ... Open All Close All Description Autosomal recessive spastic ataxia of Charlevoix-Saguenay , more commonly known as ARSACS , ...

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

    Science.gov (United States)

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

    2015-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Imed Helal

    2013-01-01

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

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

    Science.gov (United States)

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

    2011-10-01

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

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

    Directory of Open Access Journals (Sweden)

    E.A. Romão

    2006-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Reed-Gitomer B

    2014-10-01

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

  4. NEW BEST1 MUTATIONS IN AUTOSOMAL RECESSIVE BESTROPHINOPATHY

    Science.gov (United States)

    FUNG, ADRIAN T.; YZER, SUZANNE; GOLDBERG, NAOMI; WANG, HAO; NISSEN, MICHAEL; GIOVANNINI, ALFONSO; MERRIAM, JOANNA E.; BUKANOVA, ELENA N.; CAI, CAROLYN; YANNUZZI, LAWRENCE A.; TSANG, STEPHEN H.; ALLIKMETS, RANDO

    2015-01-01

    Purpose To report the ocular phenotype in patients with autosomal recessive bestrophinopathy and carriers, and to describe novel BEST1 mutations. Methods Patients with clinically suspected and subsequently genetically proven autosomal recessive bestrophinopathy underwent full ophthalmic examination and investigation with fundus autofluorescence imaging, spectral domain optical coherence tomography, electroretinography, and electrooculography. Mutation analysis of the BEST1 gene was performed through direct Sanger sequencing. Results Five affected patients from four families were identified. Mean age was 16 years (range, 6–42 years). All affected patients presented with reduced visual acuity and bilateral, hyperautofluorescent subretinal yellowish deposits within the posterior pole. Spectral domain optical coherence tomography demonstrated submacular fluid and subretinal vitelliform material in all patients. A cystoid maculopathy was seen in all but one patient. In 1 patient, the location of the vitelliform material was seen to change over a follow-up period of 3 years despite relatively stable vision. Visual acuity and fundus changes were unresponsive to topical and systemic carbonic anhydrase inhibitors and systemic steroids. Carriers had normal ocular examinations including normal fundus autofluorescence. Three novel mutations were detected. Conclusion Three novel BEST1 mutations are described, suggesting that many deleterious variants in BEST1 resulting in haploinsufficiency are still unknown. Mutations causing autosomal recessive bestrophinopathy are mostly located outside of the exons that usually harbor vitelliform macular dystrophy–associated dominant mutations. PMID:25545482

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

    OpenAIRE

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

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Fatih Firinci

    2012-01-01

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

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

    Science.gov (United States)

    Norman, Jill

    2011-10-01

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

  8. STIL mutation causes autosomal recessive microcephalic lobar holoprosencephaly.

    Science.gov (United States)

    Kakar, Naseebullah; Ahmad, Jamil; Morris-Rosendahl, Deborah J; Altmüller, Janine; Friedrich, Katrin; Barbi, Gotthold; Nürnberg, Peter; Kubisch, Christian; Dobyns, William B; Borck, Guntram

    2015-01-01

    Holoprosencephaly is a clinically and genetically heterogeneous midline brain malformation associated with neurologic manifestations including developmental delay, intellectual disability and seizures. Although mutations in the sonic hedgehog gene SHH and more than 10 other genes are known to cause holoprosencephaly, many patients remain without a molecular diagnosis. Here we show that a homozygous truncating mutation of STIL not only causes severe autosomal recessive microcephaly, but also lobar holoprosencephaly in an extended consanguineous Pakistani family. STIL mutations have previously been linked to centrosomal defects in primary microcephaly at the MCPH7 locus. Our results thus expand the clinical phenotypes associated with biallellic STIL mutations to include holoprosencephaly. PMID:25218063

  9. Mutations of the tyrosinase gene produce autosomal recessive ocular albinism

    Energy Technology Data Exchange (ETDEWEB)

    King, R.A.; Summers, C.G.; Oetting, W.S. [Univ. of Minnesota, Minneapolis, MN (United States)] [and others

    1994-09-01

    Albinism has historically been divided into ocular (OA) and oculocutaneous (OCA) types based on the presence or absence of clinically apparent skin and hair involvement in an individual with the ocular features of albinism. The major genes for OCA include the tyrosinase gene in OCA1 and the P gene in OCA2. X-linked and autosomal recessive OA have been described and the responsible genes have not been identified. We now present six Caucasian individuals who have the phenotype of autosomal recessive OA but who have OCA1 as shown by the presence of mutations of the tyrosinase. They had white or very light hair and white skin at birth, and cutaneous pigment developed in the first decade of life. At ages ranging from 1.5-23 years, hair color was dark blond to light brown. The skin had generalized pigment and well developed tan was present on the exposed arm and face skin of four. Iris pigment was present and iris translucency varied. Molecular analysis of the tyrosinase gene, using PCR amplification and direct di-deoxy sequencing showed the following mutations: E398Z/E398Q, P406S/g346a, R402E/T373K, ?/D383N, and H211N/T373K. The homozygous individual was not from a known consanguineous mating. T373K is the most common tyrosinase gene mutation in our laboratory. Three of these mutations are associated with a total loss of tyrosinase activity (g346a splice-site, T373K, and D383N), while four are associated with residual enzyme activity (H211N, R402E, E398Q, and P406S). These studies show that mutations of the tyrosinase gene can produce the phenotype of autosomal recessive OA in an individual who has normal amounts of cutaneous pigment and the ability to tan after birth. This extends the phenotypic range of OCA1 to normal cutaneous pigment after early childhood, and suggest that mutations of the tyrosinase gene account for a significant number of individuals with autosomal recessive OA.

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

    Science.gov (United States)

    Magistroni, Riccardo; Izzi, Claudia; Scolari, Francesco

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Fary Ka Elhadj

    2010-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-20

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

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

    Directory of Open Access Journals (Sweden)

    L.C. Vendramini

    2012-09-01

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

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

    Science.gov (United States)

    Bae, Kyongtae T; Grantham, Jared J

    2010-02-01

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

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

    Science.gov (United States)

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

    2008-02-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

  17. Research on autosomal dominant polycystic kidney disease in China

    Institute of Scientific and Technical Information of China (English)

    DAI Bing; MEI Chang-lin

    2006-01-01

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

  18. Mutations in PCDH21 cause autosomal recessive cone-rod dystrophy

    DEFF Research Database (Denmark)

    Østergaard, Elsebet; Batbayli, M; Dunø, Morten; Vilhelmsen, K; Rosenberg, T

    2010-01-01

    Cone-rod dystrophy is a retinal dystrophy with early loss of cone photoreceptors and a parallel or subsequent loss of rod photoreceptors. It may be syndromic, but most forms are non-syndromic with autosomal dominant, autosomal recessive or X-linked recessive inheritance.......Cone-rod dystrophy is a retinal dystrophy with early loss of cone photoreceptors and a parallel or subsequent loss of rod photoreceptors. It may be syndromic, but most forms are non-syndromic with autosomal dominant, autosomal recessive or X-linked recessive inheritance....

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

    Directory of Open Access Journals (Sweden)

    A.P. Bastos

    2011-07-01

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

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

    OpenAIRE

    Jaisuresh, K.; Bavaharan, R.

    2013-01-01

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

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

    OpenAIRE

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

    2007-01-01

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

  2. Connexin 26 and autosomal recessive non-syndromic hearing loss

    Directory of Open Access Journals (Sweden)

    Mukherjee Monisha

    2003-01-01

    Full Text Available Prelingual deafness occurs with a frequency of 1 in 1000 live births and is divided into syndromic and non-syndromic forms contributing 40 and 60% respectively. Autosomal recessive non-syndromic hearing loss (ARNSHL is responsible for 80% cases of childhood deafness. Nearly all genes localized for ARNSHL cause prelingual, severe to profound, sensorineural hearing impairment. ARNSHL is genetically heterogeneous and at least 39 loci have been identified. The most significant finding to date has been the discovery of mutations in GJB2 gene at the DFNB1 locus on chromosome 13q12 as the major cause of profound prelingual deafness. This was first reported in a Tunisian family in 1994 and thereafter in many different countries. GJB2 gene encodes the gap-junction protein, connexin 26 (Cx26, mutations in which have become the first genetic marker of inherited hearing loss. Allele-specific polymerase chain reaction (AS-PCR, single stranded conformation polymorphism (SSCP and sequencing methods have been developed for the detection of mutations in Cx26 gene. In India as well, the Cx26 mutations are being screened in families with hearing impaired children using these molecular methods. Therefore, in order to create awareness among the clinicians and the affected families; we have attempted to review the Cx26 gene mutations responsible for autosomal recessive type of non-syndromic hearing loss. The efficacy and utility of Cx26 gene analysis might open the path to proper counseling of families for carrier detection and prenatal diagnosis. It may even facilitate the development of strategies in future for the treatment of this common genetic disorder.

  3. Genetic linkage studies in autosomal recessive retinitis pigmentosa

    Energy Technology Data Exchange (ETDEWEB)

    Mansfield, D.C.; Teague, P.W.; Barber, A. [Western General Hospital, Edinburgh (United Kingdom)] [and others

    1994-09-01

    Autosomal recessive retinitis pigmentosa (arRP) is a severe retinal dystrophy characterized by night blindness, progressive constriction of the visual fields and loss of central vision in the fourth or fifth decades. The frequency of this form of retinitis pigmentosa (RP) varies in different populations. Mutations within the rhodopsin, cyclic GMP phosphodiesterase-{beta} subunit and cGMP-gated channel genes have been reported in some arRP families. The genetic loci responsible for the majority of cases have yet to be identified. Genetic heterogeneity is likely to be extensive. In order to minimize the amount of genetic heterogenity, a set of arRP families was ascertained within the South-Central Sardinian population, in which 81% of families with a known mode of inheritance show an autosomal recessive form of RP. The Sardinian population is an ethnic {open_quotes}outlier{close_quotes}, having remained relatively isolated from mainland and other cultures. Genetic linkage data has been obtained in a set of 11 Sardinian arRP kindreds containing 26 affected members. Under the assumption of genetic homogeneity, no evidence of linkage was found in the arRP kindreds using 195 markers, which excluded 62% of the genome (Z<-2). Positive lod scores were obtained with D14S80 which showed no recombination in a subset of 5 families. Heterogeneity testing using D14S80 and arRP showed no significant evidence of heterogeneity (p=0.18) but evidence of linkage ({chi}{sup 2}=3.64, p=0.028). We are currently screening the neural retina-specific leucine zipper gene (NRL) in 14q11 for mutations as a candidate locus.

  4. Autosomal recessive multiple pterygium syndrome: a new variant?

    Science.gov (United States)

    Aslan, Y; Erduran, E; Kutlu, N

    2000-07-31

    Multiple pterygium syndromes include at least 15 different entities characterized by multiple pterygia or webs of the skin and multiple congenital anomalies. We describe a female infant who presented with a distinct constellation of multiple anomalies consisting of pterygia of the inguinal, intercrural and popliteal areas, flexion contractures and arthrogryposis of some joints, craniofacial anomalies including ectropion, medial canthal web, blepharophimosis, hypoplasia of nose, oral and nasopharyngeal cavities, vocal cords and tongue, micrognathia, orolabial synechiae secondary to pterygia, low set ears, alopecia, sad and expressionless face, short neck, asymmetric nipples, anal stenosis, rectal polyp, hypoplastic labia majora, complete syndactyly of all fingers and toes, pes equinovarus, bandlike web between feet, and absence of the nails and phalangeal-palmar creases. Radiological examination showed synostosis, absence or hypoplasia of metacarpal, metatarsal and phalangeal bones on feet and hands, and hypoplasia of pelvic bones and scapulae. This pattern of anomalies does not fit entirely any of the known multiple pterygium syndromes. Autosomal recessive inheritance is most likely due to the presence of three similarly affected siblings and normal parents. PMID:10925380

  5. Isotretinoin treatment of autosomal recessive congenital ichthyosis complicated by coexisting dysferlinopathy.

    Science.gov (United States)

    Mashiah, J; Harel, A; Bitterman, O; Sagi, L; Gat, A; Fellig, Y; Ben-Shachar, S; Sprecher, E

    2016-06-01

    Consanguinity is known to be associated with an increase in the prevalence of autosomal recessive disorders such as autosomal recessive congenital ichthyosis (ARCI). ARCI often responds well to retinoid treatment. We describe a patient with ARCI who improved under isotretinoin treatment. The patient subsequently developed elevated levels of serum creatinine phosphokinase (CPK), which led to the diagnosis of a second autosomal recessive disorder, dysferlinopathy, a rare myopathy characterized by muscle weakness, decreased tendon reflexes and marked elevation of CPK levels. This report demonstrates the need for physicians to remain alert to the possible coexistence of rare and mutually relevant disorders in populations with a high rate of consanguinity. PMID:26620441

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ercan Ogreden

    2014-12-01

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

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

    OpenAIRE

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

    2009-01-01

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

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

    OpenAIRE

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

    2012-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

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

    OpenAIRE

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

    2013-01-01

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

  13. Autosomal recessive cerebellar ataxia with bull's-eye macular dystrophy.

    NARCIS (Netherlands)

    Cruysberg, J.R.M.; Eerola, K.U.; Vrijland, H.R.; Aandekerk, A.L.; Kremer, H.P.H.; Deutman, A.F.

    2002-01-01

    PURPOSE: In 1980, we published in the American Journal of Ophthalmology two siblings with hereditary ataxia and atrophic maculopathy. The report is cited in the literature as autosomal dominant cerebellar ataxia with retinal degeneration. The purpose of the present study is to document the progressi

  14. Orofacial Manifestations of Autosomal Recessive Robinow’s Syndrome: A Rare Case Report

    Science.gov (United States)

    Mali, Santosh; Dhokar, Amol; Yadav, Monica

    2016-01-01

    Robinow’s syndrome is a very rare genetic disorder which bears a resemblance to a foetal face. It is characterized by short-limbed dwarfism, defects in vertebral segmentation and abnormalities in the head, face and external genitalia. It has a genetic heterogeneity with autosomal dominant and recessive forms which relates to the severity of phenotype presentation. A rare case of an autosomal recessive form of Robinow’s syndrome is presented with emphasis on, characteristic craniofacial and intraoral manifestations to aid in diagnosis and dental management of this patient.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    Science.gov (United States)

    Horie, Shigeo

    2015-07-01

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

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

    OpenAIRE

    Lee, Seung Hun; Somlo, Stefan

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Zhiguo Mao

    2016-08-01

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

  19. Park7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36

    NARCIS (Netherlands)

    C.M. van Duijn (Cock); G.J. Breedveld (Guido); M. Horstink (Marten); L.A. Sandkuijl (Lodewijk); B.A. Oostra (Ben); J.C. van Swieten; V. Bonifati (Vincenzo); R-J.H. Galjaard (Robert-Jan); J.J. Houwing-Duistermaat (Jeanine); L. Testers; M.C.J. Dekker (Marieke); P.J.L.M. Snijders (Pieter); P. Heutink (Peter)

    2001-01-01

    textabstractAlthough the role of genetic factors in the origin of Parkinson disease has long been disputed, several genes involved in autosomal dominant and recessive forms of the disease have been localized. Mutations associated with early-onset autosomal recessive parkinsonism have been identified

  20. Park7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36.

    NARCIS (Netherlands)

    Duijn, C.M. van; Dekker, M.C.J.; Bonifati, V.; Galjaard, R.J.; Houwing-Duistermaat, J.J.; Snijders, P.J.L.M.; Testers, L.; Breedveld, G.J.; Horstink, M.W.I.M.; Sandkuijl, L.A.; Swieten, J. van; Oostra, B.A.; Heutink, P.

    2001-01-01

    Although the role of genetic factors in the origin of Parkinson disease has long been disputed, several genes involved in autosomal dominant and recessive forms of the disease have been localized. Mutations associated with early-onset autosomal recessive parkinsonism have been identified in the Park

  1. Autosomal recessive Stickler syndrome in two families is caused by mutations in the COL9A1 gene

    NARCIS (Netherlands)

    K. Nikopoulos (Konstantinos); I. Schrauwen (Isabelle); M.E.H. Simon (Marleen); R.W.J. Collin (Rob); M.A.H. Veckeneer (Marc); K. Keymolen (Kathelijn); G. van Camp (Guy); F.P.M. Cremers (Frans); L. Ingeborgh van den Born

    2011-01-01

    textabstractPurpose. To investigate COL9A1 in two families suggestive of autosomal recessive Stickler syndrome and to delineate the associated phenotype. Methods. The probands of two consanguineous autosomal recessive Stickler families were evaluated for homozygosity using SNP microarray in one and

  2. Autosomal recessive Stickler syndrome in two families is caused by mutations in the COL9A1 gene

    NARCIS (Netherlands)

    Nikopoulos, K.; Schrauwen, I.; Simon, M.; Collin, R.W.J.; Veckeneer, M.; Keymolen, K.; Camp, G. van; Cremers, F.P.M.; Born, L.I. van den

    2011-01-01

    PURPOSE: To investigate COL9A1 in two families suggestive of autosomal recessive Stickler syndrome and to delineate the associated phenotype. METHODS: The probands of two consanguineous autosomal recessive Stickler families were evaluated for homozygosity using SNP microarray in one and haplotype an

  3. An autosomal recessive syndrome of cleft palate, cardiac defect, genital anomalies, and ectrodactyly (CCGE).

    OpenAIRE

    Giannotti, A; Digilio, M C; Mingarelli, R; Dallapiccola, B.

    1995-01-01

    We report a brother and sister affected by a constellation of malformations, including cleft palate, cardiac defect, genital anomalies, and ectrodactyly (CCGE). A similar association has been reported previously by Richieri-Costa and Orquizas in a male patient born to consanguineous parents. An autosomal recessive pattern of inheritance is proposed for this syndrome.

  4. Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis

    DEFF Research Database (Denmark)

    Gribouval, Olivier; Morinière, Vincent; Pawtowski, Audrey;

    2012-01-01

    Autosomal recessive renal tubular dysgenesis (RTD) is a severe disorder of renal tubular development characterized by early onset and persistent fetal anuria leading to oligohydramnios and the Potter sequence, associated with skull ossification defects. Early death occurs in most cases from anuri...

  5. DJ-1( PARK7), a novel gene for autosomal recessive, early onset parkinsonism

    NARCIS (Netherlands)

    V. Bonifati (Vincenzo); F. Squitieri (Ferdinando); E. Krieger (Elmar); N. Vanacore (Nicola); J.C. van Swieten; A. Brice; C.M. van Duijn (Cock); G. Meco (Giuseppe); P. Heutink (Peter); B.A. Oostra (Ben); P. Rizzu (Patrizia)

    2003-01-01

    textabstractFour chromosomal loci ( PARK2, PARK6, PARK7, and PARK9) associated with autosomal recessive, early onset parkinsonism are known. We mapped the PARK7 locus to chromosome 1p36 in a large family from a genetically isolated population in the Netherlands, and confirmed this linkage in an Ital

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

    Science.gov (United States)

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

    2004-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Yilu Wang

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

  8. Infantile variant of Bartter syndrome and sensorineural deafness: A new autosomal recessive disorder

    Energy Technology Data Exchange (ETDEWEB)

    Landau, D.; Shalev, H.; Carmi, Rivka; Ohaly, M. [Univ. of the Negev, Ashkelon (Israel)

    1995-12-04

    The infantile variant of Bartter syndrome (IBS) is usually associated with maternal polyhydramnios, premature birth, postnatal polyuria and hypokalemic hypochloremic metabolic alkalosis and a typical appearance. IBS is thought to be an autosomal recessive trait. Several congenital tubular defects are associated with sensorineural deafness (SND). However, an association between the IBS and SND has not been reported so far. Here we describe 5 children of an extended consanguineous Bedouin family with IBS and SND. In 3 of the cases, the typical electrolyte imbalance and facial appearance were detected neonatally. SND was detected as early as age 1 month, suggesting either coincidental homozygotization of 2 recessive genes or a pleiotropic effect of one autosomal recessive gene. This association suggests that evaluation of SND is warranted in every case of IBS. 35 refs., 2 figs., 2 tabs.

  9. Park7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36

    OpenAIRE

    Duijn, Cock; Breedveld, Guido; Horstink, Marten; Sandkuijl, Lodewijk; Oostra, Ben; Swieten, J. C.; Bonifati, Vincenzo; Galjaard, Robert-Jan; Houwing-Duistermaat, Jeanine; Testers, L.; Dekker, Marieke; Snijders, Pieter; Heutink, Peter

    2001-01-01

    textabstractAlthough the role of genetic factors in the origin of Parkinson disease has long been disputed, several genes involved in autosomal dominant and recessive forms of the disease have been localized. Mutations associated with early-onset autosomal recessive parkinsonism have been identified in the Parkin gene, and recently a second gene, PARK6, involved in early-onset recessive parkinsonism was localized on chromosome 1p35-36. We identified a family segregating early-onset parkinsoni...

  10. Polycystic Kidney Rat Is a Novel Animal Model of Caroli’s Disease Associated with Congenital Hepatic Fibrosis

    OpenAIRE

    Sanzen, Takahiro; Harada, Kenichi; Yasoshima, Mitsue; Kawamura, Yasuhito; Ishibashi, Masahiko; Nakanuma, Yasuni

    2001-01-01

    Caroli’s disease (congenital intrahepatic biliary dilatation) associated with congenital hepatic fibrosis is an autosomal recessive polycystic kidney disease. Recently, the polycystic kidney (PCK) rat, a spontaneous mutant derived from a colony of Crj:CD rats with polycystic lesions in the liver and an autosomal recessive mode of inheritance, was reported. In the present study, the pathology of the hepatobiliary system and the biliary cell-kinetics were evaluated in fetuses (day 18 to 21 of g...

  11. ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Montecchiani, Celeste; Pedace, Lucia; Lo Giudice, Temistocle; Casella, Antonella; Mearini, Marzia; Gaudiello, Fabrizio; Pedroso, José L; Terracciano, Chiara; Caltagirone, Carlo; Massa, Roberto; St George-Hyslop, Peter H; Barsottini, Orlando G P; Kawarai, Toshitaka; Orlacchio, Antonio

    2016-01-01

    Charcot-Marie-Tooth disease is a group of hereditary peripheral neuropathies that share clinical characteristics of progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, as well as diminished tendon reflexes. Hundreds of causative DNA changes have been found, but much of the genetic basis of the disease is still unexplained. Mutations in the ALS5/SPG11/KIAA1840 gene are a frequent cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and peripheral axonal neuropathy, and account for ∼ 40% of autosomal recessive juvenile amyotrophic lateral sclerosis. The overlap of axonal Charcot-Marie-Tooth disease with both diseases, as well as the common autosomal recessive inheritance pattern of thin corpus callosum and axonal Charcot-Marie-Tooth disease in three related patients, prompted us to analyse the ALS5/SPG11/KIAA1840 gene in affected individuals with autosomal recessive axonal Charcot-Marie-Tooth disease. We investigated 28 unrelated families with autosomal recessive axonal Charcot-Marie-Tooth disease defined by clinical, electrophysiological, as well as pathological evaluation. Besides, we screened for all the known genes related to axonal autosomal recessive Charcot-Marie-Tooth disease (CMT2A2/HMSN2A2/MFN2, CMT2B1/LMNA, CMT2B2/MED25, CMT2B5/NEFL, ARCMT2F/dHMN2B/HSPB1, CMT2K/GDAP1, CMT2P/LRSAM1, CMT2R/TRIM2, CMT2S/IGHMBP2, CMT2T/HSJ1, CMTRID/COX6A1, ARAN-NM/HINT and GAN/GAN), for the genes related to autosomal recessive hereditary spastic paraplegia with thin corpus callosum and axonal peripheral neuropathy (SPG7/PGN, SPG15/ZFYVE26, SPG21/ACP33, SPG35/FA2H, SPG46/GBA2, SPG55/C12orf65 and SPG56/CYP2U1), as well as for the causative gene of peripheral neuropathy with or without agenesis of the corpus callosum (SLC12A6). Mitochondrial disorders related to Charcot-Marie-Tooth disease type 2 were also excluded by sequencing POLG and TYMP genes. An additional locus for autosomal recessive Charcot

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  13. Birth prevalence and mutation spectrum in danish patients with autosomal recessive albinism

    DEFF Research Database (Denmark)

    Grønskov, Karen; Ek, Jakob; Sand, Annie; Scheller, Rudolf; Bygum, Anette; Brixen, Kim; Brøndum-Nielsen, Karen; Rosenberg, Thomas

    2009-01-01

    PURPOSE: The study was initiated to investigate the mutation spectrum of four OCA genes and to calculate the birth prevalence in patients with autosomal recessive albinism. METHODS: Mutation analysis using dHPLC or direct DNA sequencing of TYR, OCA2, TYRP1, and MATP was performed in 62 patients...... recessive ocular albinism (AROA) based on clinical findings was 55 to 45. CONCLUSIONS: TYR is the major OCA gene in Denmark, but several patients do not have mutations in the investigated genes. A relatively large fraction of patients were observed with AROA, and of those 52% had no mutations compared with...

  14. Autosomal recessive chronic granulomatous disease caused by deletion at a dinucleotide repeat

    International Nuclear Information System (INIS)

    Chronic granulomatous disease (CGD) is a rare inherited condition rendering neutrophils incapable of killing invading pathogens. This condition is due to the failure of a multicomponent microbicidal oxidase that normally yields a low-midpoint-potential b cytochrome (cytochrome b245). Although defects in the X chromosome-linked cytochrome account for the majority of CGD patients, as many as 30% of CGD cases are due to an autosomal recessive disease. Of these, >90% have been shown to be defective in the synthesis of a 47-kDa cytosolic component of the oxidase. The authors demonstrate here in three unrelated cases of autosomal recessive CGD that the identical underlying molecular lesion is a dinucleotide deletion at a GTGT tandem repeat, corresponding to the acceptor site of the first intron - exon junction. Slippage of the DNA duplex at this site may contribute to the high frequency of defects in this gene

  15. TRPM1 Is Mutated in Patients with Autosomal-Recessive Complete Congenital Stationary Night Blindness

    OpenAIRE

    Audo, Isabelle; Kohl, Susanne; Leroy, Bart P.; Munier, Francis L.; Guillonneau, Xavier; Mohand-Saïd, Saddek; Bujakowska, Kinga; Nandrot, Emeline F.; Lorenz, Birgit; Preising, Markus; Kellner, Ulrich; Renner, Agnes B.; Bernd, Antje; Antonio, Aline; Moskova-Doumanova, Veselina

    2009-01-01

    Night vision requires signaling from rod photoreceptors to adjacent bipolar cells in the retina. Mutations in the genes NYX and GRM6, expressed in ON bipolar cells, lead to a disruption of the ON bipolar cell response. This dysfunction is present in patients with complete X-linked and autosomal-recessive congenital stationary night blindness (CSNB) and can be assessed by standard full-field electroretinography (ERG), showing severely reduced rod b-wave amplitude and slightly altered cone resp...

  16. PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans.

    OpenAIRE

    Grall, Anaïs; Guaguère, Eric; Planchais, Sandrine; Grond, Susanne; Bourrat, Emmanuelle; Hausser, Ingrid; Hitte, Christophe; Le Gallo, Matthieu; Derbois, Céline; Kim, Gwang-Jin; Lagoutte, Laëtitia; Degorce-Rubiales, Frédérique; Radner, Franz,; Thomas, Anne; Küry, Sébastien

    2012-01-01

    International audience Ichthyoses comprise a heterogeneous group of genodermatoses characterized by abnormal desquamation over the whole body, for which the genetic causes of several human forms remain unknown. We used a spontaneous dog model in the golden retriever breed, which is affected by a lamellar ichthyosis resembling human autosomal recessive congenital ichthyoses (ARCI), to carry out a genome-wide association study. We identified a homozygous insertion-deletion (indel) mutation i...

  17. Autosomal recessive limb-girdle muscular dystrophies in the Czech Republic

    OpenAIRE

    Stehlíková, Kristýna; Skálová, Daniela; Zídková, Jana; Mrázová, Lenka; Vondráček, Petr; Mazanec, Radim; Voháňka, Stanislav; Haberlová, Jana; Hermanová, Markéta; Zámečník, Josef; Souček, Ondřej; Ošlejšková, Hana; Dvořáčková, Nina; Solařová, Pavla; Fajkusová, Lenka

    2014-01-01

    Background Autosomal recessive limb-girdle muscular dystrophies (LGMD2) include a number of disorders with heterogeneous etiology that cause predominantly weakness and wasting of the shoulder and pelvic girdle muscles. In this study, we determined the frequency of LGMD subtypes within a cohort of Czech LGMD2 patients using mutational analysis of the CAPN3, FKRP, SGCA, and ANO5 genes. Methods PCR-sequencing analysis; sequence capture and targeted resequencing. Results Mutations of the CAPN3 ge...

  18. The ADAMTS18 gene is responsible for autosomal recessive early onset severe retinal dystrophy

    OpenAIRE

    Peluso Ivana; Conte Ivan; Testa Francesco; Dharmalingam Gopuraja; Pizzo Mariateresa; Collin Rob WJ; Meola Nicola; Barbato Sara; Mutarelli Margherita; Ziviello Carmela; Barbarulo Anna Maria; Nigro Vincenzo; Melone Mariarosa AB; Simonelli Francesca; Banfi Sandro

    2013-01-01

    Abstract Background Inherited retinal dystrophies, including Retinitis Pigmentosa and Leber Congenital Amaurosis among others, are a group of genetically heterogeneous disorders that lead to variable degrees of visual deficits. They can be caused by mutations in over 100 genes and there is evidence for the presence of as yet unidentified genes in a significant proportion of patients. We aimed at identifying a novel gene for an autosomal recessive form of early onset severe retinal dystrophy i...

  19. A rare case of respiratory disorders associated with two autosomal recessive diseases and male infertility

    OpenAIRE

    Mendeluk, Gabriela Ruth; Costa, Sergio López; Scigliano, Sergio; Menga, Guillermo; Demiceu, Sergio; Palaoro, Luis Alberto

    2013-01-01

    The study of nasal ciliary beat frequency (CBF) and ultrastructure may contribute to the understanding of pathognomonic cases of male infertility associated with defects in sperm motility. This study was designed to report a particular case of male infertility, characterized by the association of two respiratory autosomal recessive genetic diseases (alpha-1-antitrypsin deficiency [AAT-D] and primary ciliary dyskinesia [PCD]). A 39-year-old patient with complete sperm immotility, AAT-D, and br...

  20. A Defect in the TUSC3 Gene Is Associated with Autosomal Recessive Mental Retardation

    OpenAIRE

    Garshasbi, Masoud; Hadavi, Valeh; Habibi, Haleh; Kahrizi, Kimia; Kariminejad, Roxana; Behjati, Farkhondeh; Tzschach, Andreas; Najmabadi, Hossein; Ropers, Hans Hilger; Kuss, Andreas Walter

    2008-01-01

    Recent studies have shown that autosomal recessive mental retardation (ARMR) is extremely heterogeneous, and there is reason to believe that the number of underlying gene defects goes into the thousands. To date, however, only four genes have been implicated in nonsyndromic ARMR (NS-ARMR): PRSS12 (neurotrypsin), CRBN (cereblon), CC2D1A, and GRIK2. As part of an ongoing systematic study aiming to identify ARMR genes, we investigated a large consanguineous family comprising seven patients with ...

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

    Directory of Open Access Journals (Sweden)

    D.D. Farhud

    1999-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Kambiz Yazdanpanah

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hyunsuk Kim

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

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

    Science.gov (United States)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  6. THE SYNDROME OF AUTOSOMAL RECESSIVE PONTOCEREBELLAR HYPOPLASIA, MICROCEPHALY, AND EXTRAPYRAMIDAL DYSKINESIA (PONTOCEREBELLAR HYPOPLASIA TYPE-2) - COMPILED DATA FROM 10 PEDIGREES

    NARCIS (Netherlands)

    BARTH, PG; BLENNOW, G; LENARD, HG; BEGEER, JH; VANDERKLEY, JM; HANEFELD, F; PETERS, ACB; Valk, J.

    1995-01-01

    The syndrome of autosomal recessive pontocerebellar hypoplasia, microcephaly, severely impaired mental and motor development, and extrapyramidal dyskinesia is a distinct system degeneration, previously designated pontocerebellar hypoplasia type 2 (PCH-2). To further characterize its clinical and neu

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

    OpenAIRE

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

    2014-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    周晨晨

    2014-01-01

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

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

    OpenAIRE

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

    2013-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

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

    OpenAIRE

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

    2010-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

  13. Autosomal recessive ectodermal dysplasia: I. An undescribed dysplasia/malformation syndrome.

    Science.gov (United States)

    Bustos, T; Simosa, V; Pinto-Cisternas, J; Abramovits, W; Jolay, L; Rodriguez, L; Fernandez, L; Ramela, M

    1991-12-15

    We describe 27 individuals of 7 families related to each other with high probability who showed manifestations of ectodermal dysplasia and other anomalies affecting females as severely as males with variable expressivity. All parents were normal. These families were detected in a relatively isolated and inbred population with very small neighbouring communities from a Caribbean Sea island, Margarita Island, in Northeastern Venezuela (Nueva Esparta State). The clinical picture common to all patients could not be classified within the heterogeneous group of known ectodermal dysplasias and the published cases do not resemble our patients. We believe that this condition constitutes a newly recognized autosomal recessive dysplasia/malformation syndrome of ectodermal dysplasia. PMID:1776626

  14. Mutations in C10orf11, a Melanocyte-Differentiation Gene, Cause Autosomal-Recessive Albinism

    OpenAIRE

    Grønskov, Karen; Dooley, Christopher M.; Østergaard, Elsebet; Kelsh, Robert N.; Hansen, Lars; Levesque, Mitchell P.; Vilhelmsen, Kaj; Møllgård, Kjeld; Stemple, Derek L.; Rosenberg, Thomas

    2013-01-01

    Autosomal-recessive albinism is a hypopigmentation disorder with a broad phenotypic range. A substantial fraction of individuals with albinism remain genetically unresolved, and it has been hypothesized that more genes are to be identified. By using homozygosity mapping of an inbred Faroese family, we identified a 3.5 Mb homozygous region (10q22.2–q22.3) on chromosome 10. The region contains five protein-coding genes, and sequencing of one of these, C10orf11, revealed a nonsense mutation that...

  15. Mutations in c10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism

    DEFF Research Database (Denmark)

    Grønskov, Karen; Dooley, Christopher M; Østergaard, Elsebet;

    2013-01-01

    Autosomal-recessive albinism is a hypopigmentation disorder with a broad phenotypic range. A substantial fraction of individuals with albinism remain genetically unresolved, and it has been hypothesized that more genes are to be identified. By using homozygosity mapping of an inbred Faroese family......, we identified a 3.5 Mb homozygous region (10q22.2-q22.3) on chromosome 10. The region contains five protein-coding genes, and sequencing of one of these, C10orf11, revealed a nonsense mutation that segregated with the disease and showed a recessive inheritance pattern. Investigation of additional...... individual originating from Lithuania. Immunohistochemistry showed localization of C10orf11 in melanoblasts and melanocytes in human fetal tissue, but no localization was seen in retinal pigment epithelial cells. Knockdown of the zebrafish (Danio rerio) homolog with the use of morpholinos resulted in...

  16. A Linkage Study in 8 Pakistani Families Segregating as Autosomal Recessive Primary Microcephaly

    Directory of Open Access Journals (Sweden)

    M. Hassanullah

    2011-07-01

    Full Text Available The current study was designed to find the most frequent MCPH phenotype in inbred Pakistani families. Primary microcephaly is marked by small brain size and is usually inherited as recessive trait. In the present study, we performed linkage analysis on 8 Pakistani families with autosomal recessive primary microcephaly (MCPH and linked 6 of them to known MCPH genes/loci like MCPH1 (Microcephalin, MCPH3 (CDK5RAP2 and MCPH5 (ASPM. Majority of the families showed linkage with MCPH5, the most common MCPH locus in Pakistan. The linked families were then subjected to mutational analysis, revealing a previously known G to A transition at nucleotide position 3978 in exon 17 of ASPM gene in three of the families. To decrease its incidence, it is indispensible to train the people of the possible devastating outcome of cousin marriages and to find the carriers through carrier screening programs.

  17. A novel deletion mutation in ASPM gene in an Iranian family with autosomal recessive primary microcephaly

    Directory of Open Access Journals (Sweden)

    Elinaz AKBARIAZAR

    2013-06-01

    Full Text Available How to Cite This Article: Akbarizar E, Ebrahimpour M, Akbari S, Arzhanghi S, Abedini SS, Najmabadi H, Kahrizi K. A Novel Deletion Mutation in ASPM Gene in an Iranian Family with Autosomal Recessive Primary Microcephaly. Iran J Child Neurol.  2013 Spring;7(2:23-30. ObjectiveAutosomal recessive primary microcephaly (MCPH is a neurodevelopmental and genetically heterogeneous disorder with decreased head circumference due to the abnormality in fetal brain growth. To date, nine loci and nine genes responsible for the situation have been identified. Mutations in the ASPM gene (MCPH5 is the most common cause of MCPH. The ASPM gene with 28 exons is essential for normal mitotic spindle function in embryonic neuroblasts.Materials & MethodsWe have ascertained twenty-two consanguineous families withintellectual disability and different ethnic backgrounds from Iran. Ten out of twenty-two families showed primary microcephaly in clinical examination. We investigated MCPH5 locus using homozygosity mapping by microsatellite marker. ResultSequence analysis of exon 8 revealed a deletion of nucleotide (T in donor site of splicing site of ASPM in one family. The remaining nine families were not linked to any of the known loci. More investigation will be needed to detect the causative defect in these families.ConlusionWe detected a novel mutation in the donor splicing site of exon 8 of the ASPM gene. This deletion mutation can alter the ASPM transcript leading to functional impairment of the gene product. References1. Pattison L, Crow YJ, Deeble VJ, Jackson AP, Jafri H, Rashid Y, et al. A Fifth Locus for Primary Autosomal Recessive Microcephaly Maps to Chromosome 1q31. Am J Hum Genet 2000;67(6:1578-80.2. Darvish H, Esmaeeli-Nieh S, Monajemi G, Mohseni M, Ghasemi-Firouzabadi S, Abedini S, et al. A clinical and molecular genetic study of 112 Iranian families with primary microcephaly. Journal of Medical Genetics 2010;47(12:823-8.3. Tolmie JL, M M, JB S, D D, JM C

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

    Directory of Open Access Journals (Sweden)

    Tzeng Yi-Shiuan

    2008-12-01

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    Lee, Seung Hun; Somlo, Stefan

    2014-06-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

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

    International Nuclear Information System (INIS)

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

  3. Autosomal Recessive Congenital Ichthyosis in American Bulldogs Is Associated With NIPAL4 (ICHTHYIN) Deficiency.

    Science.gov (United States)

    Mauldin, E A; Wang, P; Evans, E; Cantner, C A; Ferracone, J D; Credille, K M; Casal, M L

    2015-07-01

    A minority of patients with nonsyndromic autosomal recessive congenital ichthyosis (ARCI) display mutations in NIPAL4 (ICHTHYIN). This protein plays a role in epidermal lipid metabolism, although the mechanism is unknown. The study describes a moderate form of ARCI in an extended pedigree of American Bulldogs that is linked to the gene encoding ichthyin. The gross phenotype was manifest as a disheveled pelage shortly after birth, generalized scaling, and adherent brown scale with erythema of the abdominal skin. Pedigree analysis indicated an autosomal recessive mode of inheritance. Ultrastructurally, the epidermis showed discontinuous lipid bilayers, unprocessed lipid within corneocytes, and abnormal lamellar bodies. Linkage analysis, performed by choosing simple sequence repeat markers and single-nucleotide polymorphisms near genes known to cause ACRI, revealed an association with NIPAL4. NIPAL4 was identified and sequenced using standard methods. No mutation was identified within the gene, but affected dogs had a SINE element 5' upstream of exon 1 in a highly conserved region. Of 545 DNA samples from American Bulldogs, 32 dogs (17 females, 15 males) were homozygous for the polymerase chain reaction fragment. All affected dogs were homozygous, with parents heterozygous for the insertion. Immunolabeling revealed an absence of ichthyin in the epidermis. This is the first description of ARCI associated with decreased expression of NIPAL4 in nonhuman species. PMID:25322746

  4. Mutations in CERS3 cause autosomal recessive congenital ichthyosis in humans.

    Science.gov (United States)

    Radner, Franz P W; Marrakchi, Slaheddine; Kirchmeier, Peter; Kim, Gwang-Jin; Ribierre, Florence; Kamoun, Bourane; Abid, Leila; Leipoldt, Michael; Turki, Hamida; Schempp, Werner; Heilig, Roland; Lathrop, Mark; Fischer, Judith

    2013-06-01

    Autosomal recessive congenital ichthyosis (ARCI) is a rare genetic disorder of the skin characterized by abnormal desquamation over the whole body. In this study we report four patients from three consanguineous Tunisian families with skin, eye, heart, and skeletal anomalies, who harbor a homozygous contiguous gene deletion syndrome on chromosome 15q26.3. Genome-wide SNP-genotyping revealed a homozygous region in all affected individuals, including the same microdeletion that partially affects two coding genes (ADAMTS17, CERS3) and abolishes a sequence for a long non-coding RNA (FLJ42289). Whereas mutations in ADAMTS17 have recently been identified in autosomal recessive Weill-Marchesani-like syndrome in humans and dogs presenting with ophthalmologic, cardiac, and skeletal abnormalities, no disease associations have been described for CERS3 (ceramide synthase 3) and FLJ42289 so far. However, analysis of additional patients with non-syndromic ARCI revealed a splice site mutation in CERS3 indicating that a defect in ceramide synthesis is causative for the present skin phenotype of our patients. Functional analysis of patient skin and in vitro differentiated keratinocytes demonstrated that mutations in CERS3 lead to a disturbed sphingolipid profile with reduced levels of epidermis-specific very long-chain ceramides that interferes with epidermal differentiation. Taken together, these data present a novel pathway involved in ARCI development and, moreover, provide the first evidence that CERS3 plays an essential role in human sphingolipid metabolism for the maintenance of epidermal lipid homeostasis. PMID:23754960

  5. Inhibitory action of chlorophyllin of autosome recessive lethals induced by irradiation

    International Nuclear Information System (INIS)

    The chlorophyllin is a sodium salt of the chlorophyll that has a strong protective action of the damage induced by different agents so much physical as chemical. In Drosophila there is reported this effect in somatic cells. In contrast, in germinal cells using tests with the sexual chromosomes has not been found such inhibitory action. For this reason, in this occasion we will refer to the effect of the lethality induced in autosome chromosomes, in particular to the chromosome II of this species. For such effect groups of males of the line Canton-S its were pre-treated for 24h with or without 69 mm of CCS and later on treaties with or without 40 Gy of gamma irradiation. The males were then subjected to the technical Cy L / Pm for the detection of recessive lethals. In the third generation the respective counts of the descendant of each one of them to determine the corresponding categories for each extracted chromosome were made. To be mendelian crosses it is expected for a normal chromosome a proportion 2:1 of individuals with genotype Cy L / +: +/+. The absence of individuals +/+ it is indicative of a lethal gene, until 10% of these individuals of each male's total descendant, it is considered that is carrying of a semi lethal gene. The sum of lethal and semi lethals constitutes the category detrimental. The obtained results indicated that the pre-treatment with CCS reduces in a significant way the frequency of induced lethals by 40 Gy of gamma rays. The fact that an effect inhibitor has not been observed in the test of recessive lethal bound to the sex obtained previously, it contrasts with the effect observed in the chromosome II, results of this study and with the one observed in the chromosome III in somatic cells. The above-mentioned shows a differential action of the CCS between sexual chromosomes and autosomal before the effect of the gamma radiation. At the moment we don't have an explanation to these evidences. To evaluate the action of the chlorophyllin

  6. A new autosomal recessive disorder of bilateral frontotemporal pachygyria without microcephaly: Report of a case and review of literature

    OpenAIRE

    Phadke Shubha; Girisha K; Phadke Rajendra

    2007-01-01

    Pachygyria is a disorder of neuronal migration. We report an Indian family with four siblings with developmental delay, infrequent seizures, normal head size and mild to moderate mental retardation. Two of them had bilaterally symmetrical frontotemporal pachygyria. Dysmorphism and neurological signs were absent in the affected subjects. Affected male and female siblings with normal parents suggests autosomal recessive mode of inheritance. We believe these cases represent a new autosomal reces...

  7. A new autosomal recessive disorder of bilateral frontotemporal pachygyria without microcephaly: Report of a case and review of literature

    Directory of Open Access Journals (Sweden)

    Phadke Shubha

    2007-01-01

    Full Text Available Pachygyria is a disorder of neuronal migration. We report an Indian family with four siblings with developmental delay, infrequent seizures, normal head size and mild to moderate mental retardation. Two of them had bilaterally symmetrical frontotemporal pachygyria. Dysmorphism and neurological signs were absent in the affected subjects. Affected male and female siblings with normal parents suggests autosomal recessive mode of inheritance. We believe these cases represent a new autosomal recessive disorder of neuronal migration. Other similar cases of lissencephaly are reviewed.

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

    Directory of Open Access Journals (Sweden)

    Faezeh Sadeghi

    2015-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Yu Chaowen

    2011-12-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    Noël, Natacha; Rieu, Philippe

    2015-07-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

  13. PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans.

    Science.gov (United States)

    Grall, Anaïs; Guaguère, Eric; Planchais, Sandrine; Grond, Susanne; Bourrat, Emmanuelle; Hausser, Ingrid; Hitte, Christophe; Le Gallo, Matthieu; Derbois, Céline; Kim, Gwang-Jin; Lagoutte, Laëtitia; Degorce-Rubiales, Frédérique; Radner, Franz P W; Thomas, Anne; Küry, Sébastien; Bensignor, Emmanuel; Fontaine, Jacques; Pin, Didier; Zimmermann, Robert; Zechner, Rudolf; Lathrop, Mark; Galibert, Francis; André, Catherine; Fischer, Judith

    2012-02-01

    Ichthyoses comprise a heterogeneous group of genodermatoses characterized by abnormal desquamation over the whole body, for which the genetic causes of several human forms remain unknown. We used a spontaneous dog model in the golden retriever breed, which is affected by a lamellar ichthyosis resembling human autosomal recessive congenital ichthyoses (ARCI), to carry out a genome-wide association study. We identified a homozygous insertion-deletion (indel) mutation in PNPLA1 that leads to a premature stop codon in all affected golden retriever dogs. We subsequently found one missense and one nonsense mutation in the catalytic domain of human PNPLA1 in six individuals with ARCI from two families. Further experiments highlighted the importance of PNPLA1 in the formation of the epidermal lipid barrier. This study identifies a new gene involved in human ichthyoses and provides insights into the localization and function of this yet uncharacterized member of the PNPLA protein family. PMID:22246504

  14. Nephrocalcinosis (Enamel Renal Syndrome) Caused by Autosomal Recessive FAM20A Mutations

    Science.gov (United States)

    Jaureguiberry, Graciana; De la Dure-Molla, Muriel; Parry, David; Quentric, Mickael; Himmerkus, Nina; Koike, Toshiyasu; Poulter, James; Klootwijk, Enriko; Robinette, Steven L.; Howie, Alexander J.; Patel, Vaksha; Figueres, Marie-Lucile; Stanescu, Horia C.; Issler, Naomi; Nicholson, Jeremy K.; Bockenhauer, Detlef; Laing, Christopher; Walsh, Stephen B.; McCredie, David A.; Povey, Sue; Asselin, Audrey; Picard, Arnaud; Coulomb, Aurore; Medlar, Alan J.; Bailleul-Forestier, Isabelle; Verloes, Alain; Le Caignec, Cedric; Roussey, Gwenaelle; Guiol, Julien; Isidor, Bertrand; Logan, Clare; Shore, Roger; Johnson, Colin; Inglehearn, Christopher; Al-Bahlani, Suhaila; Schmittbuhl, Matthieu; Clauss, François; Huckert, Mathilde; Laugel, Virginie; Ginglinger, Emmanuelle; Pajarola, Sandra; Spartà, Giuseppina; Bartholdi, Deborah; Rauch, Anita; Addor, Marie-Claude; Yamaguti, Paulo M.; Safatle, Heloisa P.; Acevedo, Ana Carolina; Martelli-Júnior, Hercílio; dos Santos Netos, Pedro E.; Coletta, Ricardo D.; Gruessel, Sandra; Sandmann, Carolin; Ruehmann, Denise; Langman, Craig B.; Scheinman, Steven J.; Ozdemir-Ozenen, Didem; Hart, Thomas C.; Hart, P. Suzanne; Neugebauer, Ute; Schlatter, Eberhard; Houillier, Pascal; Gahl, William A.; Vikkula, Miikka; Bloch-Zupan, Agnès; Bleich, Markus; Kitagawa, Hiroshi; Unwin, Robert J.; Mighell, Alan; Berdal, Ariane; Kleta, Robert

    2013-01-01

    Background/Aims Calcium homeostasis requires regulated cellular and interstitial systems interacting to modulate the activity and movement of this ion. Disruption of these systems in the kidney results in nephrocalcinosis and nephrolithiasis, important medical problems whose pathogenesis is incompletely understood. Methods We investigated 25 patients from 16 families with unexplained nephrocalcinosis and characteristic dental defects (amelogenesis imperfecta, gingival hyperplasia, impaired tooth eruption). To identify the causative gene, we performed genome-wide linkage analysis, exome capture, next-generation sequencing, and Sanger sequencing. Results All patients had bi-allelic FAM20A mutations segregating with the disease; 20 different mutations were identified. Conclusions This au-tosomal recessive disorder, also known as enamel renal syndrome, of FAM20A causes nephrocalcinosis and amelogenesis imperfecta. We speculate that all individuals with biallelic FAM20A mutations will eventually show nephrocalcinosis. PMID:23434854

  15. Autosomal recessive PGM3 mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment

    Science.gov (United States)

    Zhang, Yu; Yu, Xiaomin; Ichikawa, Mie; Lyons, Jonathan J.; Datta, Shrimati; Lamborn, Ian T.; Jing, Huie; Kim, Emily S.; Biancalana, Matthew; Wolfe, Lynne A.; DiMaggio, Thomas; Matthews, Helen F.; Kranick, Sarah M.; Stone, Kelly D.; Holland, Steven M.; Reich, Daniel S.; Hughes, Jason D.; Mehmet, Huseyin; McElwee, Joshua; Freeman, Alexandra F.; Freeze, Hudson H.; Su, Helen C.; Milner, Joshua D.

    2014-01-01

    Background Identifying genetic syndromes that lead to significant atopic disease can open new pathways for investigation and intervention in allergy. Objective To define a genetic syndrome of severe atopy, elevated serum IgE, immune deficiency, autoimmunity, and motor and neurocognitive impairment. Methods Eight patients from two families who had similar syndromic features were studied. Thorough clinical evaluations, including brain MRI and sensory evoked potentials, were performed. Peripheral lymphocyte flow cytometry, antibody responses, and T cell cytokine production were measured. Whole exome sequencing was performed to identify disease-causing mutations. Immunoblotting, qRT-PCR, enzymatic assays, nucleotide sugar and sugar phosphate analyses along with MALDI-TOF mass spectrometry of glycans were used to determine the molecular consequences of the mutations. Results Marked atopy and autoimmunity were associated with increased TH2 and TH17 cytokine production by CD4+ T cells. Bacterial and viral infection susceptibility were noted along with T cell lymphopenia, particularly of CD8+ T cells, and reduced memory B cells. Apparent brain hypomyelination resulted in markedly delayed evoked potentials and likely contributed to neurological abnormalities. Disease segregated with novel autosomal recessive mutations in a single gene, phosphoglucomutase 3 (PGM3). Although PGM3 protein expression was variably diminished, impaired function was demonstrated by decreased enzyme activity and reduced UDP-GlcNAc, along with decreased O- and N-linked protein glycosylation in patients’ cells. These results define a new Congenital Disorder of Glycosylation. Conclusions Autosomal recessive, hypomorphic PGM3 mutations underlie a disorder of severe atopy, immune deficiency, autoimmunity, intellectual disability and hypomyelination. PMID:24589341

  16. Autosomal recessive primary microcephaly (MCPH: clinical manifestations, genetic heterogeneity and mutation continuum

    Directory of Open Access Journals (Sweden)

    Hassan Muhammad J

    2011-06-01

    Full Text Available Abstract Autosomal Recessive Primary Microcephaly (MCPH is a rare disorder of neurogenic mitosis characterized by reduced head circumference at birth with variable degree of mental retardation. In MCPH patients, brain size reduced to almost one-third of its original volume due to reduced number of generated cerebral cortical neurons during embryonic neurogensis. So far, seven genetic loci (MCPH1-7 for this condition have been mapped with seven corresponding genes (MCPH1, WDR62, CDK5RAP2, CEP152, ASPM, CENPJ, and STIL identified from different world populations. Contribution of ASPM and WDR62 gene mutations in MCPH World wide is more than 50%. By and large, primary microcephaly patients are phenotypically indistinguishable, however, recent studies in patients with mutations in MCPH1, WDR62 and ASPM genes showed a broader clinical and/or cellular phenotype. It has been proposed that mutations in MCPH genes can cause the disease phenotype by disturbing: 1 orientation of mitotic spindles, 2 chromosome condensation mechanism during embryonic neurogenesis, 3 DNA damage-response signaling, 4 transcriptional regulations and microtubule dynamics, 5 certain unknown centrosomal mechanisms that control the number of neurons generated by neural precursor cells. Recent discoveries of mammalian models for MCPH have open up horizons for researchers to add more knowledge regarding the etiology and pathophysiology of MCPH. High incidence of MCPH in Pakistani population reflects the most probable involvement of consanguinity. Genetic counseling and clinical management through carrier detection/prenatal diagnosis in MCPH families can help reducing the incidence of this autosomal recessive disorder.

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

    OpenAIRE

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

    2015-01-01

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

  18. Clinical Characteristics and Disease Predictors of a Large Chinese Cohort of Patients with Autosomal Dominant Polycystic Kidney Disease

    OpenAIRE

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

    2014-01-01

    Objective Autosomal dominant polycystic kidney disease (ADPKD) is a relentlessly progressing form of chronic kidney disease for which there is no cure. The aim of this study was to characterize Chinese patients with ADPKD and to identify the factors which predict cyst growth and renal functional deterioration. Methods To analyze disease predicting factors we performed a prospective longitudinal observational study in a cohort of 541 Chinese patients with ADPKD and an eGFR ≥30 ml/min/1.73 m2. ...

  19. Mutations in MFSD8, encoding a lysosomal membrane protein, are associated with nonsyndromic autosomal recessive macular dystrophy

    NARCIS (Netherlands)

    Roosing, S.; Born, L.I. van den; Sangermano, R.; Banfi, S.; Koenekoop, R.K.; Zonneveld-Vrieling, M.N.; Klaver, C.C.; Lith-Verhoeven, J.J. van; Cremers, F.P.M.; Hollander, A.I. den; Hoyng, C.B.

    2015-01-01

    PURPOSE: This study aimed to identify the genetic defects in 2 families with autosomal recessive macular dystrophy with central cone involvement. DESIGN: Case series. PARTICIPANTS: Two families and a cohort of 244 individuals with various inherited maculopathies and cone disorders. METHODS: Genome-w

  20. A homozygous mutation in a consanguineous family consolidates the role of ALDH1A3 in autosomal recessive microphthalmia

    DEFF Research Database (Denmark)

    Roos, L; Fang, M; Dali, C; Jensen, H; Christoffersen, N; Wu, B; Zhang, J; Xu, R; Harris, P; Xu, X; Grønskov, K; Tümer, Z

    2013-01-01

    identification of new genes. Very recently, homozygous variations within ALDH1A3 have been associated with autosomal recessive microphthalmia with or without cysts or coloboma, and with variable subphenotypes of developmental delay/autism spectrum disorder in eight families. In a consanguineous family where...

  1. Adaptor Protein Complex 4 Deficiency Causes Severe Autosomal-Recessive Intellectual Disability, Progressive Spastic Paraplegia, Shy Character, and Short Stature

    OpenAIRE

    Abou Jamra, Rami; Philippe, Orianne; Raas-Rothschild, Annick; Eck, Sebastian H.; Graf, Elisabeth; Buchert, Rebecca; Borck, Guntram; Ekici, Arif; Brockschmidt, Felix F.; Nöthen, Markus M.; Munnich, Arnold; Strom, Tim M.; Reis, Andre; Colleaux, Laurence

    2011-01-01

    Intellectual disability inherited in an autosomal-recessive fashion represents an important fraction of severe cognitive-dysfunction disorders. Yet, the extreme heterogeneity of these conditions markedly hampers gene identification. Here, we report on eight affected individuals who were from three consanguineous families and presented with severe intellectual disability, absent speech, shy character, stereotypic laughter, muscular hypotonia that progressed to spastic paraplegia, microcephaly,...

  2. Hypomorphic mutations in PGAP2, encoding a GPI-anchor-remodeling protein, cause autosomal-recessive intellectual disability

    DEFF Research Database (Denmark)

    Hansen, Lars; Tawamie, Hasan; Murakami, Yoshiko; Mang, Yuan; ur Rehman, Shoaib; Buchert, Rebecca; Schaffer, Stefanie; Muhammad, Safia; Bak, Mads; Nöthen, Markus M; Bennett, Eric P; Maeda, Yusuke; Aigner, Michael; Reis, André; Kinoshita, Taroh; Tommerup, Niels; Baig, Shahid Mahmood; Abou Jamra, Rami

    2013-01-01

    alkaline phosphatase (ALP). We performed autozygosity mapping and ultra-deep sequencing followed by stringent filtering and identified two homozygous PGAP2 alterations, p.Tyr99Cys and p.Arg177Pro, in seven offspring with nonspecific autosomal-recessive intellectual disability from two consanguineous...

  3. Cerebellar Cognitive Affective Syndrome and Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay : A Report of Two Male Sibs

    NARCIS (Netherlands)

    Verhoeven, Willem M. A.; Egger, Jos I. M.; Ahmed, Amir I. M.; Kremer, Berry P. H.; Vermeer, Sascha; van de Warrenburg, Bart P. C.

    2012-01-01

    Background: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare neurodegenerative disorder caused by mutations in the SACS gene (13q12) encoding the protein sacsin. It is characterized by early-onset cerebellar ataxia, lower limb spasticity, sensorimotor axonal polyneuropath

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-11-22

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

  5. 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

  6. Libyan Boy with Autosomal Recessive Trait (P22-phox Defect of Chronic Granulomatous Disease

    Directory of Open Access Journals (Sweden)

    Ilka Schulze

    2006-09-01

    Full Text Available Chronic granulomatous disease (CGD is a primary immune deficiency disorder of the phagocytes. In this disorder, phagocytic cells (polymorphonuclear leukocytes and monocytes cannot produce active oxygen metabolites, and therefore, cannot destroy the ingested intracellular bacteria. Clinically, patients with CGD usually have recurrent bacterial and fungal infections causing abscess and granuloma formation in the skin, lymph nodes and visceral organs.In this report, we present a boy from Libya with a rare autosomal recessive trait of CGD (defect of p22-phox who has chronic lung disease following multiple severe pneumonia attacks. The case we present suffered from bloody diarrhea since the third month of his life. He also had recurrent episodes of fever, and later, developed persistent cervical lymphadenitis and failure to gain weight. CGD is a very rare condition worldwide. It is also not recognized here in Libya, and usually not in the list of differential diagnosis for chronic pulmonary infections. We advise that pediatricians and general practitioners who treat chronic cases of lung diseases (with or without chronic diarrhea should consider primary immunodeficiency disorders in the hope that early diagnosis and treatment may prevent chronic complications especially of the respiratory tract. Furthermore, we state that, to the best of our knowledge, this is the first documented case of CGD from Libya.

  7. Naturally- and experimentally-designed restorations of the Parkin gene deficit in autosomal recessive juvenile parkinsonism

    Energy Technology Data Exchange (ETDEWEB)

    Asai, Hirohide; Hirano, Makito; Kiriyama, Takao; Ikeda, Masanori [Department of Neurology, Faculty of Medicine, Nara Medical University School of Medicine (Japan); Ueno, Satoshi, E-mail: sueno@naramed-u.ac.jp [Department of Neurology, Faculty of Medicine, Nara Medical University School of Medicine (Japan)

    2010-01-01

    Intranuclear events due to mutations in the Parkin gene remain elusive in autosomal recessive juvenile parkinsonism (ARJP). We identified a mutant PARKIN protein in fibroblast cultures from a pair of siblings with ARJP who were homozygous for the exon 4-deleted Parkin gene. Disease was mild in one patient and debilitating in the other. The detected mutant, encoded by a transcript lacking exon 3 as well as exon 4, is an in-frame deletion that removes 121 aa, resulting in a 344-aa protein (PaDel3,4). Cell culture and transfection studies revealed negative correlations between expression levels of PaDel3,4 and those of cell cycle proteins, including cyclin E, CDK2, ppRb, and E2F-1, and demonstrated that GFP-PaDel3,4 entered nucleus and ubiquitinated cyclin E as a part of SCF{sup hSel-10} ligase complex in the patient cells. In addition, nuclear localization signal-tagged PaDel3,4 expressed in the transfected patient cells most effectively ubiquitinated cyclin E and reduced DNA damage, protecting cells from oxidative stress. Antisense-oligonucleotide treatment promoted skipping of exon 3 and thus generated PaDel3,4, increasing cell survival. Collectively, we propose that naturally- and experimentally-induced exon skipping at least partly restores the mutant Parkin gene deficit, providing a molecular basis for the development of therapeutic exon skipping.

  8. A newly recognized autosomal recessive syndrome affecting neurologic function and vision.

    Science.gov (United States)

    Salih, Mustafa A; Tzschach, Andreas; Oystreck, Darren T; Hassan, Hamdy H; AlDrees, Abdulmajeed; Elmalik, Salah A; El Khashab, Heba Y; Wienker, Thomas F; Abu-Amero, Khaled K; Bosley, Thomas M

    2013-06-01

    Genetic factors represent an important etiologic group in the causation of intellectual disability. We describe a Saudi Arabian family with closley related parents in which four of six children were affected by a congenital cognitive disturbance. The four individuals (aged 18, 16, 13, and 2 years when last examined) had motor and cognitive delay with seizures in early childhood, and three of the four (sparing only the youngest child) had progressive, severe cognitive decline with spasticity. Two affected children had ocular malformations, and the three older children had progressive visual loss. The youngest had normal globes with good functional vision when last examined but exhibited the oculodigital sign, which may signify a subclinical visual deficit. A potentially deleterious nucleotide change (c.1A>G; p.Met1Val) in the C12orf57 gene was homozygous in all affected individuals, heterozygous in the parents, and absent in an unaffected sibling and >350 normal individuals. This gene has no known function. This family manifests a autosomal recessive syndrome with some phenotypic variability that includes abnormal development of brain and eyes, delayed cognitive and motor milestones, seizures, and a severe cognitive and visual decline that is associated with a homozygous variant in a newly identified gene. PMID:23633300

  9. Distribution of skeletal muscle involvement in autosomal recessive distal muscular dystrophy

    International Nuclear Information System (INIS)

    Distribution of skeletal muscle involvement in 5 cases with autosomal recessive distal muscular dystrophy was studied clinically and by computed tomography (CT). Manual muscle test showed muscle involvement with a predilection for flexors in the lower leg and adductors in the thigh. Flexion and extension of the thigh and the lower leg was impaired to similar degree. In progressed cases, neck flexors and trunk muscles were also affected mildly. CT disclosed more clearly the preferential involvement of flexors in the lower leg, and involvement of both hamstrings · adductors group and extensors group of the thigh to similar degree. However, m. popliteus was curiously well preserved. In addition, there was a stage showing high density and hypertrophy of m. sartorius, m. gracilis, m. adductor, m. biceps femoris, m. semimenbranosus, m. semitendinosus or m. rectus femoris, which in thought to be compensatory hypertrophy. M. gluteus minimus in the pelvic girdle and m. dorsi proprii in the trunk were also liable to be affected. The CT findings are regarded as characteristic features noted clearly before muscle weakness and atrophy become apparent clinically. CT is very useful for distinguishing distal muscular dystrophy from rimmed vacuolar distal myopathy in which m. quadriceps femoris and flexors of the lower leg are usually well preserved without compensatory hypertrophy on CT. (author)

  10. Successful twin pregnancy in a patient with parkin-associated autosomal recessive juvenile parkinsonism

    Directory of Open Access Journals (Sweden)

    Takakuwa Koichi

    2011-06-01

    Full Text Available Abstract Background Pregnancy in patients with Parkinson disease is a rare occurrence. To the best of our knowledge, the effect of pregnancy as well as treatment in genetically confirmed autosomal recessive juvenile parkinsonism (ARJP has never been reported. Here, we report the first case of pregnancy in a patient with ARJP associated with a parkin gene mutation, ARJP/PARK2. Case presentation A 27-year-old woman with ARJP/PARK2 was diagnosed as having a spontaneous dichorionic/diamniotic twin pregnancy. Exacerbation of motor disability was noted between ovulation and menstruation before pregnancy as well as during late pregnancy, suggesting that her parkinsonism might have been influenced by fluctuations in the levels of endogenous sex hormones. During the organogenesis period, she was only treated with levodopa/carbidopa, although she continued to receive inpatient hospital care for assistance in the activities of daily living. After the organogenesis period, she was administered sufficient amounts of antiparkinsonian drugs. She delivered healthy male twins, and psychomotor development of both the babies was normal at the age of 2 years. Conclusion Pregnancy may worsen the symptoms of ARJP/PARK2, although appropriate treatments with antiparkinsonian drugs and adequate assistance in the activities of daily living might enable successful pregnancy and birth of healthy children.

  11. Where do we stand in trial readiness for autosomal recessive limb girdle muscular dystrophies?

    Science.gov (United States)

    Straub, Volker; Bertoli, Marta

    2016-02-01

    Autosomal recessive limb girdle muscular dystrophies (LGMD2) are a group of genetically heterogeneous diseases that are typically characterised by progressive weakness and wasting of the shoulder and pelvic girdle muscles. Many of the more than 20 different conditions show overlapping clinical features with other forms of muscular dystrophy, congenital, myofibrillar or even distal myopathies and also with acquired muscle diseases. Although individually extremely rare, all types of LGMD2 together form an important differential diagnostic group among neuromuscular diseases. Despite improved diagnostics and pathomechanistic insight, a curative therapy is currently lacking for any of these diseases. Medical care consists of the symptomatic treatment of complications, aiming to improve life expectancy and quality of life. Besides well characterised pre-clinical tools like animal models and cell culture assays, the determinants of successful drug development programmes for rare diseases include a good understanding of the phenotype and natural history of the disease, the existence of clinically relevant outcome measures, guidance on care standards, up to date patient registries, and, ideally, biomarkers that can help assess disease severity or drug response. Strong patient organisations driving research and successful partnerships between academia, advocacy, industry and regulatory authorities can also help accelerate the elaboration of clinical trials. All these determinants constitute aspects of translational research efforts and influence patient access to therapies. Here we review the current status of determinants of successful drug development programmes for LGMD2, and the challenges of translating promising therapeutic strategies into effective and accessible treatments for patients. PMID:26810373

  12. The ADAMTS18 gene is responsible for autosomal recessive early onset severe retinal dystrophy

    Directory of Open Access Journals (Sweden)

    Peluso Ivana

    2013-01-01

    Full Text Available Abstract Background Inherited retinal dystrophies, including Retinitis Pigmentosa and Leber Congenital Amaurosis among others, are a group of genetically heterogeneous disorders that lead to variable degrees of visual deficits. They can be caused by mutations in over 100 genes and there is evidence for the presence of as yet unidentified genes in a significant proportion of patients. We aimed at identifying a novel gene for an autosomal recessive form of early onset severe retinal dystrophy in a patient carrying no previously described mutations in known genes. Methods An integrated strategy including homozygosity mapping and whole exome sequencing was used to identify the responsible mutation. Functional tests were performed in the medaka fish (Oryzias latipes model organism to gain further insight into the pathogenic role of the ADAMTS18 gene in eye and central nervous system (CNS dysfunction. Results This study identified, in the analyzed patient, a homozygous missense mutation in the ADAMTS18 gene, which was recently linked to Knobloch syndrome, a rare developmental disorder that affects the eye and the occipital skull. In vivo gene knockdown performed in medaka fish confirmed both that the mutation has a pathogenic role and that the inactivation of this gene has a deleterious effect on photoreceptor cell function. Conclusion This study reveals that mutations in the ADAMTS18 gene can cause a broad phenotypic spectrum of eye disorders and contribute to shed further light on the complexity of retinal diseases.

  13. Naturally- and experimentally-designed restorations of the Parkin gene deficit in autosomal recessive juvenile parkinsonism

    International Nuclear Information System (INIS)

    Intranuclear events due to mutations in the Parkin gene remain elusive in autosomal recessive juvenile parkinsonism (ARJP). We identified a mutant PARKIN protein in fibroblast cultures from a pair of siblings with ARJP who were homozygous for the exon 4-deleted Parkin gene. Disease was mild in one patient and debilitating in the other. The detected mutant, encoded by a transcript lacking exon 3 as well as exon 4, is an in-frame deletion that removes 121 aa, resulting in a 344-aa protein (PaDel3,4). Cell culture and transfection studies revealed negative correlations between expression levels of PaDel3,4 and those of cell cycle proteins, including cyclin E, CDK2, ppRb, and E2F-1, and demonstrated that GFP-PaDel3,4 entered nucleus and ubiquitinated cyclin E as a part of SCFhSel-10 ligase complex in the patient cells. In addition, nuclear localization signal-tagged PaDel3,4 expressed in the transfected patient cells most effectively ubiquitinated cyclin E and reduced DNA damage, protecting cells from oxidative stress. Antisense-oligonucleotide treatment promoted skipping of exon 3 and thus generated PaDel3,4, increasing cell survival. Collectively, we propose that naturally- and experimentally-induced exon skipping at least partly restores the mutant Parkin gene deficit, providing a molecular basis for the development of therapeutic exon skipping.

  14. Whole exome analysis identifies frequent CNGA1 mutations in Japanese population with autosomal recessive retinitis pigmentosa.

    Directory of Open Access Journals (Sweden)

    Satoshi Katagiri

    Full Text Available OBJECTIVE: The purpose of this study was to investigate frequent disease-causing gene mutations in autosomal recessive retinitis pigmentosa (arRP in the Japanese population. METHODS: In total, 99 Japanese patients with non-syndromic and unrelated arRP or sporadic RP (spRP were recruited in this study and ophthalmic examinations were conducted for the diagnosis of RP. Among these patients, whole exome sequencing analysis of 30 RP patients and direct sequencing screening of all CNGA1 exons of the other 69 RP patients were performed. RESULTS: Whole exome sequencing of 30 arRP/spRP patients identified disease-causing gene mutations of CNGA1 (four patients, EYS (three patients and SAG (one patient in eight patients and potential disease-causing gene variants of USH2A (two patients, EYS (one patient, TULP1 (one patient and C2orf71 (one patient in five patients. Screening of an additional 69 arRP/spRP patients for the CNGA1 gene mutation revealed one patient with a homozygous mutation. CONCLUSIONS: This is the first identification of CNGA1 mutations in arRP Japanese patients. The frequency of CNGA1 gene mutation was 5.1% (5/99 patients. CNGA1 mutations are one of the most frequent arRP-causing mutations in Japanese patients.

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  16. Founder mutations in the lipase H (LIPH) gene in families with autosomal recessive woolly hair/hypotrichosis

    OpenAIRE

    Shimomura, Yutaka; Wajid, Muhammad; Zlotogorski, Abraham; Lee, Young Jin; Rice, Robert H.; Christiano, Angela M.

    2009-01-01

    Autosomal recessive woolly hair (ARWH)/hypotrichosis is a hereditary hair disorder which is characterized by tightly curled hair, and is occasionally associated with sparse hair. ARWH can be caused by mutations in the P2RY5 or lipase H (LIPH) gene. Disruption of both genes results in phenotypes with features of both WH and hypotrichosis. In this study, we identified two Guyanese families with ARWH. Both families are of recent Indian descent. Mutation analysis resulted in the identification of...

  17. Autosomal recessive woolly hair with hypotrichosis caused by a novel homozygous mutation in the P2RY5 gene

    OpenAIRE

    Shimomura, Yutaka; Garzon, Maria C.; Christiano, Angela M.

    2008-01-01

    During the last decade, several causative genes for hereditary hair diseases have been identified, which have disclosed the molecular mechanisms involved in hair follicle morphogenesis and cycling. We and others recently reported that mutations in the P2RY5 gene, encoding an orphan G protein-coupled receptor, underlie autosomal recessive woolly hair and/or hypotrichosis. Although these findings clearly reveal the involvement of P2RY5 mutations in hereditary hair diseases, the clinical manifes...

  18. Identification of two novel mutations in CDHR1 in consanguineous Spanish families with autosomal recessive retinal dystrophy

    OpenAIRE

    Konstantinos Nikopoulos; Almudena Avila-Fernandez; Marta Corton; Maria Isabel Lopez-Molina; Raquel Perez-Carro; Lara Bontadelli; Silvio Alessandro Di Gioia; Olga Zurita; Blanca Garcia-Sandoval; Carlo Rivolta; Carmen Ayuso

    2015-01-01

    Inherited retinal dystrophies present extensive phenotypic and genetic heterogeneity, posing a challenge for patients’ molecular and clinical diagnoses. In this study, we wanted to clinically characterize and investigate the molecular etiology of an atypical form of autosomal recessive retinal dystrophy in two consanguineous Spanish families. Affected members of the respective families exhibited an array of clinical features including reduced visual acuity, photophobia, defective color vision...

  19. Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS: typical clinical and neuroimaging features in a Brazilian family

    Directory of Open Access Journals (Sweden)

    J L Pedroso

    2011-01-01

    Full Text Available Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS is a neurodegenerative disorder characterized by late-infantile onset spastic ataxia and other neurological features. ARSACS has a high prevalence in northeastern Quebec, Canada. Several ARSACS cases have been reported outside Canada in recent decades. This is the first report of typical clinical and neuroimaging features in a Brazilian family with probable diagnosis of ARSACS.

  20. Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS): typical clinical and neuroimaging features in a Brazilian family

    OpenAIRE

    Pedroso, J.L.; P Braga-Neto; A Abrahão; R L M Rivero; C Abdalla; N. Abdala; O G P Barsottini

    2011-01-01

    Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurodegenerative disorder characterized by late-infantile onset spastic ataxia and other neurological features. ARSACS has a high prevalence in northeastern Quebec, Canada. Several ARSACS cases have been reported outside Canada in recent decades. This is the first report of typical clinical and neuroimaging features in a Brazilian family with probable diagnosis of ARSACS.

  1. Mutation in WNT10A Is Associated with an Autosomal Recessive Ectodermal Dysplasia: The Odonto-onycho-dermal Dysplasia

    OpenAIRE

    Adaimy, Lynn ; Chouery, Eliane ; Mégarbané, Hala ; Mroueh, Salman ; Delague, Valérie ; Nicolas, Elsa ; Belguith, Hanen ; de Mazancourt, Philippe ; Mégarbané, André 

    2007-01-01

    Odonto-onycho-dermal dysplasia is a rare autosomal recessive syndrome in which the presenting phenotype is dry hair, severe hypodontia, smooth tongue with marked reduction of fungiform and filiform papillae, onychodysplasia, keratoderma and hyperhidrosis of palms and soles, and hyperkeratosis of the skin. We studied three consanguineous Lebanese Muslim Shiite families that included six individuals affected with odonto-onycho-dermal dysplasia. Using a homozygosity-mapping strategy, we assigned...

  2. Mutations in GANAB, Encoding the Glucosidase IIα Subunit, Cause Autosomal-Dominant Polycystic Kidney and Liver Disease.

    Science.gov (United States)

    Porath, Binu; Gainullin, Vladimir G; Cornec-Le Gall, Emilie; Dillinger, Elizabeth K; Heyer, Christina M; Hopp, Katharina; Edwards, Marie E; Madsen, Charles D; Mauritz, Sarah R; Banks, Carly J; Baheti, Saurabh; Reddy, Bharathi; Herrero, José Ignacio; Bañales, Jesús M; Hogan, Marie C; Tasic, Velibor; Watnick, Terry J; Chapman, Arlene B; Vigneau, Cécile; Lavainne, Frédéric; Audrézet, Marie-Pierre; Ferec, Claude; Le Meur, Yannick; Torres, Vicente E; Harris, Peter C

    2016-06-01

    Autosomal-dominant polycystic kidney disease (ADPKD) is a common, progressive, adult-onset disease that is an important cause of end-stage renal disease (ESRD), which requires transplantation or dialysis. Mutations in PKD1 or PKD2 (∼85% and ∼15% of resolved cases, respectively) are the known causes of ADPKD. Extrarenal manifestations include an increased level of intracranial aneurysms and polycystic liver disease (PLD), which can be severe and associated with significant morbidity. Autosomal-dominant PLD (ADPLD) with no or very few renal cysts is a separate disorder caused by PRKCSH, SEC63, or LRP5 mutations. After screening, 7%-10% of ADPKD-affected and ∼50% of ADPLD-affected families were genetically unresolved (GUR), suggesting further genetic heterogeneity of both disorders. Whole-exome sequencing of six GUR ADPKD-affected families identified one with a missense mutation in GANAB, encoding glucosidase II subunit α (GIIα). Because PRKCSH encodes GIIβ, GANAB is a strong ADPKD and ADPLD candidate gene. Sanger screening of 321 additional GUR families identified eight further likely mutations (six truncating), and a total of 20 affected individuals were identified in seven ADPKD- and two ADPLD-affected families. The phenotype was mild PKD and variable, including severe, PLD. Analysis of GANAB-null cells showed an absolute requirement of GIIα for maturation and surface and ciliary localization of the ADPKD proteins (PC1 and PC2), and reduced mature PC1 was seen in GANAB(+/-) cells. PC1 surface localization in GANAB(-/-) cells was rescued by wild-type, but not mutant, GIIα. Overall, we show that GANAB mutations cause ADPKD and ADPLD and that the cystogenesis is most likely driven by defects in PC1 maturation. PMID:27259053

  3. Autosomal-Recessive Hearing Impairment Due to Rare Missense Variants within S1PR2

    Science.gov (United States)

    Santos-Cortez, Regie Lyn P.; Faridi, Rabia; Rehman, Atteeq U.; Lee, Kwanghyuk; Ansar, Muhammad; Wang, Xin; Morell, Robert J.; Isaacson, Rivka; Belyantseva, Inna A.; Dai, Hang; Acharya, Anushree; Qaiser, Tanveer A.; Muhammad, Dost; Ali, Rana Amjad; Shams, Sulaiman; Hassan, Muhammad Jawad; Shahzad, Shaheen; Raza, Syed Irfan; Bashir, Zil-e-Huma; Smith, Joshua D.; Nickerson, Deborah A.; Bamshad, Michael J.; Riazuddin, Sheikh; Ahmad, Wasim; Friedman, Thomas B.; Leal, Suzanne M.

    2016-01-01

    The sphingosine-1-phosphate receptors (S1PRs) are a well-studied class of transmembrane G protein-coupled sphingolipid receptors that mediate multiple cellular processes. However, S1PRs have not been previously reported to be involved in the genetic etiology of human traits. S1PR2 lies within the autosomal-recessive nonsyndromic hearing impairment (ARNSHI) locus DFNB68 on 19p13.2. From exome sequence data we identified two pathogenic S1PR2 variants, c.323G>C (p.Arg108Pro) and c.419A>G (p.Tyr140Cys). Each of these variants co-segregates with congenital profound hearing impairment in consanguineous Pakistani families with maximum LOD scores of 6.4 for family DEM4154 and 3.3 for family PKDF1400. Neither S1PR2 missense variant was reported among ∼120,000 chromosomes in the Exome Aggregation Consortium database, in 76 unrelated Pakistani exomes, or in 720 Pakistani control chromosomes. Both DNA variants affect highly conserved residues of S1PR2 and are predicted to be damaging by multiple bioinformatics tools. Molecular modeling predicts that these variants affect binding of sphingosine-1-phosphate (p.Arg108Pro) and G protein docking (p.Tyr140Cys). In the previously reported S1pr2−/− mice, stria vascularis abnormalities, organ of Corti degeneration, and profound hearing loss were observed. Additionally, hair cell defects were seen in both knockout mice and morphant zebrafish. Family PKDF1400 presents with ARNSHI, which is consistent with the lack of gross malformations in S1pr2−/− mice, whereas family DEM4154 has lower limb malformations in addition to hearing loss. Our findings suggest the possibility of developing therapies against hair cell damage (e.g., from ototoxic drugs) through targeted stimulation of S1PR2. PMID:26805784

  4. A large animal model for CNGB1 autosomal recessive retinitis pigmentosa.

    Directory of Open Access Journals (Sweden)

    Paige A Winkler

    Full Text Available Retinal dystrophies in dogs are invaluable models of human disease. Progressive retinal atrophy (PRA is the canine equivalent of retinitis pigmentosa (RP. Similar to RP, PRA is a genetically heterogenous condition. We investigated PRA in the Papillon breed of dog using homozygosity mapping and haplotype construction of single nucleotide polymorphisms within a small family group to identify potential positional candidate genes. Based on the phenotypic similarities between the PRA-affected Papillons, mouse models and human patients, CNGB1 was selected as the most promising positional candidate gene. CNGB1 was sequenced and a complex mutation consisting of the combination of a one basepair deletion and a 6 basepair insertion was identified in exon 26 (c.2387delA;2389_2390insAGCTAC leading to a frameshift and premature stop codon. Immunohistochemistry (IHC of pre-degenerate retinal sections from a young affected dog showed absence of labeling using a C-terminal CNGB1 antibody. Whereas an antibody directed against the N-terminus of the protein, which also recognizes the glutamic acid rich proteins arising from alternative splicing of the CNGB1 transcript (upstream of the premature stop codon, labeled rod outer segments. CNGB1 combines with CNGA1 to form the rod cyclic nucleotide gated channel and previous studies have shown the requirement of CNGB1 for normal targeting of CNGA1 to the rod outer segment. In keeping with these previous observations, IHC showed a lack of detectable CNGA1 protein in the rod outer segments of the affected dog. A population study did not identify the CNGB1 mutation in PRA-affected dogs in other breeds and documented that the CNGB1 mutation accounts for ~70% of cases of Papillon PRA in our PRA-affected canine DNA bank. CNGB1 mutations are one cause of autosomal recessive RP making the CNGB1 mutant dog a valuable large animal model of the condition.

  5. A Founder Mutation in VPS11 Causes an Autosomal Recessive Leukoencephalopathy Linked to Autophagic Defects

    Science.gov (United States)

    Schaffner, Adam; Fedick, Anastasia; Kaye, Lauren E.; Liao, Jun; Yachelevich, Naomi; Chu, Mary-Lynn; Boles, Richard G.; Moran, Ellen; Tokita, Mari; Gorman, Elizabeth; Zhang, Wei; Xia, Fan; Leduc, Magalie; Yang, Yaping; Eng, Christine; Wong, Lee-Jun; Schiffmann, Raphael; Diaz, George A.; Kornreich, Ruth; Thummel, Ryan; Wasserstein, Melissa; Yue, Zhenyu; Edelmann, Lisa

    2016-01-01

    Genetic leukoencephalopathies (gLEs) are a group of heterogeneous disorders with white matter abnormalities affecting the central nervous system (CNS). The causative mutation in ~50% of gLEs is unknown. Using whole exome sequencing (WES), we identified homozygosity for a missense variant, VPS11: c.2536T>G (p.C846G), as the genetic cause of a leukoencephalopathy syndrome in five individuals from three unrelated Ashkenazi Jewish (AJ) families. All five patients exhibited highly concordant disease progression characterized by infantile onset leukoencephalopathy with brain white matter abnormalities, severe motor impairment, cortical blindness, intellectual disability, and seizures. The carrier frequency of the VPS11: c.2536T>G variant is 1:250 in the AJ population (n = 2,026). VPS11 protein is a core component of HOPS (homotypic fusion and protein sorting) and CORVET (class C core vacuole/endosome tethering) protein complexes involved in membrane trafficking and fusion of the lysosomes and endosomes. The cysteine 846 resides in an evolutionarily conserved cysteine-rich RING-H2 domain in carboxyl terminal regions of VPS11 proteins. Our data shows that the C846G mutation causes aberrant ubiquitination and accelerated turnover of VPS11 protein as well as compromised VPS11-VPS18 complex assembly, suggesting a loss of function in the mutant protein. Reduced VPS11 expression leads to an impaired autophagic activity in human cells. Importantly, zebrafish harboring a vps11 mutation with truncated RING-H2 domain demonstrated a significant reduction in CNS myelination following extensive neuronal death in the hindbrain and midbrain. Thus, our study reveals a defect in VPS11 as the underlying etiology for an autosomal recessive leukoencephalopathy disorder associated with a dysfunctional autophagy-lysosome trafficking pathway. PMID:27120463

  6. Novel and recurrent AID mutations underlie prevalent autosomal recessive form of HIGM in consanguineous patients.

    Science.gov (United States)

    Ouadani, Hanen; Ben-Mustapha, Imen; Ben-ali, Meriem; Ben-khemis, Leila; Larguèche, Beya; Boussoffara, Raoudha; Maalej, Sonia; Fetni, Ilhem; Hassayoun, Saida; Mahfoudh, Abdelmajid; Mellouli, Fethi; Yalaoui, Sadok; Masmoudi, Hatem; Bejaoui, Mohamed; Barbouche, Mohamed-Ridha

    2016-01-01

    Immunoglobulin class switch recombination deficiencies (Ig-CSR-D) are characterized by normal or elevated serum IgM level and absence of IgG, IgA, and IgE. Most reported cases are due to X-linked CD40L deficiency. Activation-induced cytidine deaminase deficiency is the most frequent autosomal recessive form, whereas CD40 deficiency is more rare. Herein, we present the first North African study on hyper IgM (HIGM) syndrome including 16 Tunisian patients. Phenotypic and genetic studies allowed us to determine their molecular basis. Three CD40LG mutations have been identified including two novels (c.348_351dup and c.782_*2del) and one already reported mutation (g.6182G>A). No mutation has been found in another patient despite the lack of CD40L expression. Interestingly, three AICDA mutations have been identified in 11 patients. Two mutations were novel (c.91T>C and c.389A>C found in one and five patients respectively), and one previously reported splicing mutation (c.156+1T>G) was found in five patients. Only one CD40-deficient patient, bearing a novel mutation (c.109T>G), has been identified. Thus, unlike previous reports, AID deficiency is the most frequent underlying molecular basis (68%) of Ig-CSR-D in Tunisian patients. This finding and the presence of specific recurrent mutations are probably due to the critical role played by inbreeding in North African populations. PMID:26545377

  7. A defect in the TUSC3 gene is associated with autosomal recessive mental retardation.

    Science.gov (United States)

    Garshasbi, Masoud; Hadavi, Valeh; Habibi, Haleh; Kahrizi, Kimia; Kariminejad, Roxana; Behjati, Farkhondeh; Tzschach, Andreas; Najmabadi, Hossein; Ropers, Hans Hilger; Kuss, Andreas Walter

    2008-05-01

    Recent studies have shown that autosomal recessive mental retardation (ARMR) is extremely heterogeneous, and there is reason to believe that the number of underlying gene defects goes into the thousands. To date, however, only four genes have been implicated in nonsyndromic ARMR (NS-ARMR): PRSS12 (neurotrypsin), CRBN (cereblon), CC2D1A, and GRIK2. As part of an ongoing systematic study aiming to identify ARMR genes, we investigated a large consanguineous family comprising seven patients with nonsyndromic ARMR in four sibships. Genome-wide SNP typing enabled us to map the relevant genetic defect to a 4.6 Mbp interval on chromosome 8. Haplotype analyses and copy-number studies led to the identification of a homozygous deletion partly removing TUSC3 (N33) in all patients. All obligate carriers of this family were heterozygous, but none of 192 unrelated healthy individuals from the same population carried this deletion. We excluded other disease-causing mutations in the coding regions of all genes within the linkage interval by sequencing; moreover, we verified the complete absence of a functional TUSC3 transcript in all patients through RT-PCR. TUSC3 is thought to encode a subunit of the endoplasmic reticulum-bound oligosaccharyltransferase complex that catalyzes a pivotal step in the protein N-glycosylation process. Our data suggest that in contrast to other genetic defects of glycosylation, inactivation of TUSC3 causes nonsyndromic MR, a conclusion that is supported by a separate report in this issue of AJHG. TUSC3 is only the fifth gene implicated in NS-ARMR and the first for which mutations have been reported in more than one family. PMID:18452889

  8. Mutations in the Beta Propeller WDR72 Cause Autosomal-Recessive Hypomaturation Amelogenesis Imperfecta

    Science.gov (United States)

    El-Sayed, Walid; Parry, David A.; Shore, Roger C.; Ahmed, Mushtaq; Jafri, Hussain; Rashid, Yasmin; Al-Bahlani, Suhaila; Al Harasi, Sharifa; Kirkham, Jennifer; Inglehearn, Chris F.; Mighell, Alan J.

    2009-01-01

    Healthy dental enamel is the hardest and most highly mineralized human tissue. Though acellular, nonvital, and without capacity for turnover or repair, it can nevertheless last a lifetime. Amelogenesis imperfecta (AI) is a collective term for failure of normal enamel development, covering diverse clinical phenotypes that typically show Mendelian inheritance patterns. One subset, known as hypomaturation AI, is characterised by near-normal volumes of organic enamel matrix but with weak, creamy-brown opaque enamel that fails prematurely after tooth eruption. Mutations in genes critical to enamel matrix formation have been documented, but current understanding of other key events in enamel biomineralization is limited. We investigated autosomal-recessive hypomaturation AI in a consanguineous Pakistani family. A whole-genome SNP autozygosity screen identified a locus on chromosome 15q21.3. Sequencing candidate genes revealed a point mutation in the poorly characterized WDR72 gene. Screening of WDR72 in a panel of nine additional hypomaturation AI families revealed the same mutation in a second, apparently unrelated, Pakistani family and two further nonsense mutations in Omani families. Immunohistochemistry confirmed intracellular localization in maturation-stage ameloblasts. WDR72 function is unknown, but as a putative β propeller is expected to be a scaffold for protein-protein interactions. The nearest homolog, WDR7, is involved in vesicle mobilization and Ca2+-dependent exocytosis at synapses. Vesicle trafficking is important in maturation-stage ameloblasts with respect to secretion into immature enamel and removal of cleaved enamel matrix proteins via endocytosis. This raises the intriguing possibility that WDR72 is critical to ameloblast vesicle turnover during enamel maturation. PMID:19853237

  9. New approaches to the autosomal recessive polycystic kidney disease patient with dual kidney-liver complications.

    Science.gov (United States)

    Telega, Grzegorz; Cronin, David; Avner, Ellis D

    2013-06-01

    Improved neonatal medical care and renal replacement technology have improved the long-term survival of patients with ARPKD. Ten-yr survival of those surviving the first year of life is reported to be 82% and is continuing to improve further. However, despite increases in overall survival and improved treatment of systemic hypertension and other complications of their renal disease, nearly 50% of survivors will develop ESRD within the first decade of life. In addition to renal pathology, patients with ARPKD develop ductal plate malformations with cystic dilation of intra- and extrahepatic bile ducts resulting in CHF and Caroli syndrome. Many patients with CHF will develop portal hypertension with resulting esophageal varices, splenomegaly, hypersplenism, protein losing enteropathy, and gastrointestinal bleeding. Management of portal hypertension may require EBL of esophageal varices or porto-systemic shunting. Complications of hepatic involvement can include ascending cholangitis, cholestasis with malabsorption of fat-soluble vitamins, and rarely benign or malignant liver tumors. Patients with ARPKD who eventually reach ESRD, and ultimately require kidney transplantation, present a unique set of complications related to their underlying hepato-biliary disease. In this review, we focus on new approaches to these challenging patients, including the indications for liver transplantation in ARPKD patients with severe chronic kidney disease awaiting kidney transplant. While survival in patients with ARPKD and isolated kidney transplant is comparable to that of age-matched pediatric patients who have received kidney transplants due to other primary renal diseases, 64-80% of the mortality occurring in ARPKD kidney transplant patients is attributed to cholangitis/sepsis, which is related to their hepato-biliary disease. Recent data demonstrate that surgical mortality among pediatric liver transplant recipients is decreased to <10% at one yr. The immunosuppressive regimen used for kidney transplant recipients is adequate for most liver transplant recipients. We therefore suggest that in a select group of ARPKD patients with recurrent cholangitis or complications of portal hypertension, combined liver-kidney transplant is a viable option. Although further study is necessary to confirm our approach, we believe that combined liver-kidney transplantation can potentially decrease overall mortality and morbidity in carefully selected ARPKD patients with ESRD and clinically significant CHF. PMID:23593929

  10. Autosomal recessive polycystic kidney disease and congenital hepatic fibrosis (ARPKD/CHF)

    Energy Technology Data Exchange (ETDEWEB)

    Turkbey, Baris; Choyke, Peter L. [National Institutes of Health, Molecular Imaging Program, National Cancer Institute, Bethesda, MD (United States); Ocak, Iclal [National Institutes of Health, Molecular Imaging Program, National Cancer Institute, Bethesda, MD (United States); University of Pittsburgh Medical Center, Department of Radiology, Pittsburgh, PA (United States); Daryanani, Kailash [National Institutes of Health, Clinical Center, Department of Radiology, Bethesda, MD (United States); Font-Montgomery, Esperanza; Lukose, Linda; Bryant, Joy; Tuchman, Maya; Gahl, William A. [National Institutes of Health, National Human Genome Research Institute, Medical Genetics Branch, Bethesda, MD (United States); Mohan, Parvathi [George Washington University, Department of Pediatric Gastroenterology, Washington, DC (United States); Heller, Theo [National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD (United States); Gunay-Aygun, Meral [National Institutes of Health, National Human Genome Research Institute, Medical Genetics Branch, Bethesda, MD (United States); National Institutes of Health, Intramural Program, Office of Rare Diseases, Office of the Directors, Bethesda, MD (United States)

    2009-02-15

    ARPKD/CHF is an inherited disease characterized by non-obstructive fusiform dilatation of the renal collecting ducts leading to enlarged spongiform kidneys and ductal plate malformation of the liver resulting in congenital hepatic fibrosis. ARPKD/CHF has a broad spectrum of clinical presentations involving the kidney and liver. Imaging plays an important role in the diagnosis and follow-up of ARPKD/CHF. Combined use of conventional and high-resolution US with MR cholangiography in ARPKD/CHF patients allows detailed definition of the extent of kidney and hepatobiliary manifestations without requiring ionizing radiation and contrast agents. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Dongping Chen

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

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

    OpenAIRE

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

    2015-01-01

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

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

    OpenAIRE

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

    2016-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

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

    OpenAIRE

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

    2011-01-01

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

  16. A Case of Autosomal Recessive Woolly Hair/Hypotrichosis with Alternation in Severity: Deterioration and Improvement with Age

    OpenAIRE

    Matsuno, Naoko; Kunisada, Makoto; Kanki, Haruhisa; Simomura, Yutaka; Nishigori, Chikako

    2013-01-01

    Autosomal recessive woolly hair/hypotrichosis (ARWH/H) is a nonsyndromic hair abnormality characterized by sparse, short and curly hair (WH/H). We report the case of a 3-year-old female, with no consanguineous ancestry, who exhibited WH/H. Normal hair was observed at birth, but severe hair loss had developed within the first 6 months; however, her hair density had improved somewhat by age 3. Light microscopy showed hair shaft invaginations, and polarized light microscopy suggested complete me...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-03-01

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

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Cheema Abdul

    2008-11-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2013-11-01

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

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

    Science.gov (United States)

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

    2010-07-01

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2002-01-01

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

  5. Novel mutations confirm that COL11A2 is responsible for autosomal recessive non-syndromic hearing loss DFNB53.

    Science.gov (United States)

    Chakchouk, Imen; Grati, M'hamed; Bademci, Guney; Bensaid, Mariem; Ma, Qi; Chakroun, Amine; Foster, Joseph; Yan, Denise; Duman, Duygu; Diaz-Horta, Oscar; Ghorbel, Abdelmonem; Mittal, Rahul; Farooq, Amjad; Tekin, Mustafa; Masmoudi, Saber; Liu, Xue Zhong

    2015-08-01

    Hearing loss (HL) is a major public health issue. It is clinically and genetically heterogeneous.The identification of the causal mutation is important for early diagnosis, clinical follow-up, and genetic counseling. HL due to mutations in COL11A2, encoding collagen type XI alpha-2, can be non-syndromic autosomal-dominant or autosomal-recessive, and also syndromic as in Otospondylomegaepiphyseal Dysplasia, Stickler syndrome type III, and Weissenbacher-Zweymuller syndrome. However, thus far only one mutation co-segregating with autosomal recessive non-syndromic hearing loss (ARNSHL) in a single family has been reported. In this study, whole exome sequencing of two consanguineous families with ARNSHL from Tunisia and Turkey revealed two novel causative COL11A2 mutations, c.109G > T (p.Ala37Ser) and c.2662C > A (p.Pro888Thr). The variants identified co-segregated with deafness in both families. All homozygous individuals in those families had early onset profound hearing loss across all frequencies without syndromic findings. The variants are predicted to be damaging the protein function. The p.Pro888Thr mutation affects a -Gly-X-Y- triplet repeat motif. The novel p.Ala37Ser is the first missense mutation located in the NC4 domain of the COL11A2 protein. Structural model suggests that this mutation will likely obliterate, or at least partially compromise, the ability of NC4 domain to interact with its cognate ligands. In conclusion, we confirm that COL11A2 mutations cause ARNSHL and broaden the mutation spectrum that may shed new light on genotype-phenotype correlation for the associated phenotypes and clinical follow-up. PMID:25633957

  6. Autozygosity mapping of a large consanguineous Pakistani family reveals a novel non-syndromic autosomal recessive mental retardation locus on 11p15-tel

    DEFF Research Database (Denmark)

    Rehman, Shoaib ur; Baig, Shahid Mahmood; Eiberg, Hans;

    2011-01-01

    Autosomal recessive inherited mental retardation is an extremely heterogeneous disease and accounts for approximately 25% of all non-syndromic mental retardation cases. Autozygosity mapping of a large consanguineous Pakistani family revealed a novel locus for non-syndromic autosomal recessive...... mental retardation (NS-ARMR). The affected individuals showed low IQ and cognitive impairment without any neurological, skeletal, and biochemical abnormalities. All known NS-ARMR genes were excluded by STS markers, so autozygosity mapping by microarray single-nucleotide polymorphism (SNP) analysis were......¿=¿3.31 was calculated for the mapped region. These results suggest a novel genetic locus, MRT17, for NS-ARMR....

  7. Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci.

    Science.gov (United States)

    Najmabadi, Hossein; Motazacker, Mohammad Mahdi; Garshasbi, Masoud; Kahrizi, Kimia; Tzschach, Andreas; Chen, Wei; Behjati, Farkhondeh; Hadavi, Valeh; Nieh, Sahar Esmaeeli; Abedini, Seyedeh Sedigheh; Vazifehmand, Reza; Firouzabadi, Saghar Ghasemi; Jamali, Payman; Falah, Masoumeh; Seifati, Seyed Morteza; Grüters, Annette; Lenzner, Steffen; Jensen, Lars R; Rüschendorf, Franz; Kuss, Andreas W; Ropers, H Hilger

    2007-03-01

    Autosomal recessive gene defects are arguably the most important, but least studied genetic causes of severe cognitive dysfunction. Homozygosity mapping in 78 consanguineous Iranian families with nonsyndromic autosomal recessive mental retardation (NS-ARMR) has enabled us to determine the chromosomal localization of at least 8 novel gene loci for this condition. Our data suggest that in the Iranian population NS-ARMR is very heterogeneous, and they argue against the existence of frequent gene defects that account for more than a few percent of the cases. PMID:17120046

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

    Directory of Open Access Journals (Sweden)

    Andrea Guala

    2007-01-01

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

  9. The Bowen-Conradi syndrome -- a highly lethal autosomal recessive syndrome of microcephaly, micrognathia, low birth weight, and joint deformities.

    Science.gov (United States)

    Hunter, A G; Woerner, S J; Montalvo-Hicks, L D; Fowlow, S B; Haslam, R H; Metcalf, P J; Lowry, R B

    1979-01-01

    This paper describes six Hutterite children from five families who appear to have been affected by the same syndrome that was described in two brothers by Bowen and Conradi [1]. Our additional cases confirm that the major features of the syndrome include porportionate intrauterine growth retardation, microcephaly, micrognathia, a prominent nose, rocker-bottom feet, joint limitation, and failure to thrive, with death within the first year of life. Bowen-Conradi syndrome is an autosomal recessive trait and pedigree records show that all six families now known are related to each other through two couples born in the late 1700s but that there are additional earlier possible sources of the responsible gene. The differential diagnosis of this syndrome is discussed. PMID:484596

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Andreas D Kistler

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

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

    Science.gov (United States)

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

    2014-01-01

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

  13. Autosomal recessive mental retardation: homozygosity mapping identifies 27 single linkage intervals, at least 14 novel loci and several mutation hotspots.

    Science.gov (United States)

    Kuss, Andreas Walter; Garshasbi, Masoud; Kahrizi, Kimia; Tzschach, Andreas; Behjati, Farkhondeh; Darvish, Hossein; Abbasi-Moheb, Lia; Puettmann, Lucia; Zecha, Agnes; Weissmann, Robert; Hu, Hao; Mohseni, Marzieh; Abedini, Seyedeh Sedigheh; Rajab, Anna; Hertzberg, Christoph; Wieczorek, Dagmar; Ullmann, Reinhard; Ghasemi-Firouzabadi, Saghar; Banihashemi, Susan; Arzhangi, Sanaz; Hadavi, Valeh; Bahrami-Monajemi, Gholamreza; Kasiri, Mahboubeh; Falah, Masoumeh; Nikuei, Pooneh; Dehghan, Atefeh; Sobhani, Masoumeh; Jamali, Payman; Ropers, Hans Hilger; Najmabadi, Hossein

    2011-02-01

    Mental retardation (MR) has a worldwide prevalence of around 2% and is a frequent cause of severe disability. Significant excess of MR in the progeny of consanguineous matings as well as functional considerations suggest that autosomal recessive forms of MR (ARMR) must be relatively common. To shed more light on the causes of autosomal recessive MR (ARMR), we have set out in 2003 to perform systematic clinical studies and autozygosity mapping in large consanguineous Iranian families with non-syndromic ARMR (NS-ARMR). As previously reported (Najmabadi et al. in Hum Genet 121:43-48, 2007), this led us to the identification of 12 novel ARMR loci, 8 of which had a significant LOD score (OMIM: MRT5-12). In the meantime, we and others have found causative gene defects in two of these intervals. Moreover, as reported here, tripling the size of our cohort has enabled us to identify 27 additional unrelated families with NS-ARMR and single-linkage intervals; 14 of these define novel loci for non-syndromic ARMR. Altogether, 13 out of 39 single linkage intervals observed in our cohort were found to cluster at 6 different loci on chromosomes, i.e., 1p34, 4q27, 5p15, 9q34, 11p11-q13 and 19q13, respectively. Five of these clusters consist of two significantly overlapping linkage intervals, and on chr 1p34, three single linkage intervals coincide, including the previously described MRT12 locus. The probability for this distribution to be due to chance is only 1.14 × 10(-5), as shown by Monte Carlo simulation. Thus, in contrast to our previous conclusions, these novel data indicate that common molecular causes of NS-ARMR do exist, and in the Iranian population, the most frequent ones may well account for several percent of the patients. These findings will be instrumental in the identification of the underlying genes. PMID:21063731

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

    International Nuclear Information System (INIS)

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  16. A Register-Based Study of Diseases With an Autosomal Recessive Origin in Small Children in Denmark According to Maternal Country of Origin

    DEFF Research Database (Denmark)

    Gundlund, Anna; Hansen, Anne Vinkel; Pedersen, Grete Skøtt;

    2015-01-01

    information on consanguinity is lacking, this suggestion is difficult to test. With an indirect approach, we addressed this question by comparing the risk of diseases with autosomal recessive inheritance in children born in Denmark of Danish-born women and of women born in these five countries, respectively...

  17. Autosomal-recessive posterior microphthalmos is caused by mutations in PRSS56, a gene encoding a trypsin-like serine protease

    DEFF Research Database (Denmark)

    Gal, Andreas; Rau, Isabella; El Matri, Leila;

    2011-01-01

    Posterior microphthalmos (MCOP) is a rare isolated developmental anomaly of the eye characterized by extreme hyperopia due to short axial length. The population of the Faroe Islands shows a high prevalence of an autosomal-recessive form (arMCOP) of the disease. Based on published linkage data, we...

  18. Screening for homozygosity by descent in families with autosomal recessive retinitis pigmentosa

    Indian Academy of Sciences (India)

    Kota Lalitha; Subhadra Jalali; Tejas Kadakia; Chitra Kannabiran

    2002-08-01

    Retinitis pigmentosa (RP) is a genetically heterogeneous disease and an important cause of blindness in the state of Andhra Pradesh in India. In an attempt to identify the disease locus in families with the recessive form of the disease, we used the approach of screening for homozygosity by descent in offspring of consanguineous and nonconsanguineous families with RP. Microsatellite markers closely flanking 21 known candidate genes for RP were genotyped in parents and affected offspring to determine whether there was homozygosity at these loci that was shared by affected individuals of a family. This screening approach may be a rapid preliminary method to test known loci for possible cosegregation with disease.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hartmut P.H. Neumann

    2012-10-01

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

  1. Inhibition of Intrahepatic Bile Duct Dilation of the Polycystic Kidney Rat with a Novel Tyrosine Kinase Inhibitor Gefitinib

    OpenAIRE

    Sato, Yasunori; Harada, Kenichi; Furubo, Shinichi; Kizawa, Kazuo; Sanzen, Takahiro; Yasoshima, Mitsue; Ozaki, Satoru; Isse, Kumiko; Sasaki, Motoko; Nakanuma, Yasuni

    2006-01-01

    The polycystic kidney (PCK) rat represents a liver and kidney cyst pathology corresponding to Caroli’s disease with congenital hepatic fibrosis and autosomal recessive polycystic kidney disease. We previously reported that an epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib (Iressa), significantly inhibited the abnormal growth of biliary epithelial cells of PCK rats in vitro. This study investigated the effects of gefitinib on cyst pathogenesis of the PCK rat both in vitr...

  2. Mutations in the histamine N-methyltransferase gene, HNMT, are associated with nonsyndromic autosomal recessive intellectual disability.

    Science.gov (United States)

    Heidari, Abolfazl; Tongsook, Chanakan; Najafipour, Reza; Musante, Luciana; Vasli, Nasim; Garshasbi, Masoud; Hu, Hao; Mittal, Kirti; McNaughton, Amy J M; Sritharan, Kumudesh; Hudson, Melissa; Stehr, Henning; Talebi, Saeid; Moradi, Mohammad; Darvish, Hossein; Arshad Rafiq, Muhammad; Mozhdehipanah, Hossein; Rashidinejad, Ali; Samiei, Shahram; Ghadami, Mohsen; Windpassinger, Christian; Gillessen-Kaesbach, Gabriele; Tzschach, Andreas; Ahmed, Iltaf; Mikhailov, Anna; Stavropoulos, D James; Carter, Melissa T; Keshavarz, Soraya; Ayub, Muhammad; Najmabadi, Hossein; Liu, Xudong; Ropers, Hans Hilger; Macheroux, Peter; Vincent, John B

    2015-10-15

    Histamine (HA) acts as a neurotransmitter in the brain, which participates in the regulation of many biological processes including inflammation, gastric acid secretion and neuromodulation. The enzyme histamine N-methyltransferase (HNMT) inactivates HA by transferring a methyl group from S-adenosyl-l-methionine to HA, and is the only well-known pathway for termination of neurotransmission actions of HA in mammalian central nervous system. We performed autozygosity mapping followed by targeted exome sequencing and identified two homozygous HNMT alterations, p.Gly60Asp and p.Leu208Pro, in patients affected with nonsyndromic autosomal recessive intellectual disability from two unrelated consanguineous families of Turkish and Kurdish ancestry, respectively. We verified the complete absence of a functional HNMT in patients using in vitro toxicology assay. Using mutant and wild-type DNA constructs as well as in silico protein modeling, we confirmed that p.Gly60Asp disrupts the enzymatic activity of the protein, and that p.Leu208Pro results in reduced protein stability, resulting in decreased HA inactivation. Our results highlight the importance of inclusion of HNMT for genetic testing of individuals presenting with intellectual disability. PMID:26206890

  3. A mutation in the FOXE3 gene causes congenital primary aphakia in an autosomal recessive consanguineous Pakistani family

    DEFF Research Database (Denmark)

    Anjum, Iram; Eiberg, Hans; Baig, Shahid Mahmood;

    2010-01-01

    PURPOSE: Aphakia is the complete absence of any lens in the eye, either due to surgical removal of the lens as a result of a perforating wound or ulcer, or due to a congenital anomaly. The purpose of this study was to elucidate the molecular genetics for a large consanguineous Pakistani family wi...... quite primitive in origin since the same mutation is responsible for the same phenotypic outcome in two families of geographically different descent.......PURPOSE: Aphakia is the complete absence of any lens in the eye, either due to surgical removal of the lens as a result of a perforating wound or ulcer, or due to a congenital anomaly. The purpose of this study was to elucidate the molecular genetics for a large consanguineous Pakistani family with...... a clear aphakia phenotype. METHODS: The initial homozygosity screening of the family was extended to all the known autosomal recessive cataract loci in order to exclude the possibility of surgical cataract removal leading to aphakia. The screening was performed using polymorphic nucleotide repeat...

  4. Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia.

    Science.gov (United States)

    Adaimy, Lynn; Chouery, Eliane; Megarbane, Hala; Mroueh, Salman; Delague, Valerie; Nicolas, Elsa; Belguith, Hanen; de Mazancourt, Philippe; Megarbane, Andre

    2007-10-01

    Odonto-onycho-dermal dysplasia is a rare autosomal recessive syndrome in which the presenting phenotype is dry hair, severe hypodontia, smooth tongue with marked reduction of fungiform and filiform papillae, onychodysplasia, keratoderma and hyperhidrosis of palms and soles, and hyperkeratosis of the skin. We studied three consanguineous Lebanese Muslim Shiite families that included six individuals affected with odonto-onycho-dermal dysplasia. Using a homozygosity-mapping strategy, we assigned the disease locus to an ~9-cM region at chromosome 2q35-q36.2, located between markers rs16853834 and D2S353, with a maximum multipoint LOD score of 5.7. Screening of candidate genes in this region led us to identify the same c.697G-->T (p.Glu233X) homozygous nonsense mutation in exon 3 of the WNT10A gene in all patients. At the protein level, the mutation is predicted to result in a premature truncated protein of 232 aa instead of 417 aa. This is the first report to our knowledge of a human phenotype resulting from a mutation in WNT10A, and it is the first demonstration of an ectodermal dysplasia caused by an altered WNT signaling pathway, expanding the list of WNT-related diseases. PMID:17847007

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  6. Possible influences on the expression of X chromosome-linked dystrophin abnormalities by heterozygosity for autosomal recessive Fukuyama congenital muscular dystrophy.

    OpenAIRE

    Beggs, A H; Neumann, P E; Arahata, K; Arikawa, E; Nonaka, I; Anderson, M S; Kunkel, L. M.

    1992-01-01

    Abnormalities of dystrophin, a cytoskeletal protein of muscle and nerve, are generally considered specific for Duchenne and Becker muscular dystrophy. However, several patients have recently been identified with dystrophin deficiency who, before dystrophin testing, were considered to have Fukuyama congenital muscular dystrophy (FCMD) on the basis of clinical findings. Epidemiologic data suggest that only 1/3500 males with autosomal recessive FCMD should have abnormal dystrophin. To explain th...

  7. GPR179 is required for depolarizing bipolar cell function and is mutated in autosomal-recessive complete congenital stationary night blindness

    OpenAIRE

    Peachey, Neal S.; Ray, Thomas A.; Florijn, Ralph; Rowe, Lucy B.; Sjoerdsma, Trijntje; Contreras-Alcantara, Susana; Baba, Kenkichi; Tosini, Gianluca; Pozdeyev, Nikita; Iuvone, P. Michael; Bojang, Pasano; Pearring, Jillian N.; Simonsz, Huibert Jan; van Genderen, Maria; Birch, David G.

    2012-01-01

    textabstractComplete congenital stationary night blindness (cCSNB) is a clinically and genetically heterogeneous group of retinal disorders characterized by nonprogressive impairment of night vision, absence of the electroretinogram (ERG) b-wave, and variable degrees of involvement of other visual functions. We report here that mutations in GPR179, encoding an orphan G protein receptor, underlie a form of autosomal-recessive cCSNB. The Gpr179nob5/nob5mouse model was initially discovered by th...

  8. Ultrasound-guided percutaneous drainage and sclerotherapy in a patient with isolated autosomal dominant polycystic liver disease

    Directory of Open Access Journals (Sweden)

    Ana Barbado-Cano

    2015-03-01

    Full Text Available Isolated polycystic liver disease (IPLD is a rare genetic condition characterized by the presence of multiple liver cysts with no association with polycystic kidney disease. Most patients are asymptomatic and acute complications (cyst torsion, bleeding, infection are uncommon. Imaging techniques, including abdominal ultrasounds, computerized axial tomography, and magnetic resonance imaging, represent a vital diagnostic modality. They are also useful for therapy support in this disease. Below we report a peculiar case of a female patient recently diagnosed with IPLD who, having received treatment with ultrasound-guided percutaneous drainage and sclerotherapy for a giant liver cyst, showed symptom and laboratory improvement.

  9. Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy.

    Science.gov (United States)

    Lesage, Suzanne; Drouet, Valérie; Majounie, Elisa; Deramecourt, Vincent; Jacoupy, Maxime; Nicolas, Aude; Cormier-Dequaire, Florence; Hassoun, Sidi Mohamed; Pujol, Claire; Ciura, Sorana; Erpapazoglou, Zoi; Usenko, Tatiana; Maurage, Claude-Alain; Sahbatou, Mourad; Liebau, Stefan; Ding, Jinhui; Bilgic, Basar; Emre, Murat; Erginel-Unaltuna, Nihan; Guven, Gamze; Tison, François; Tranchant, Christine; Vidailhet, Marie; Corvol, Jean-Christophe; Krack, Paul; Leutenegger, Anne-Louise; Nalls, Michael A; Hernandez, Dena G; Heutink, Peter; Gibbs, J Raphael; Hardy, John; Wood, Nicholas W; Gasser, Thomas; Durr, Alexandra; Deleuze, Jean-François; Tazir, Meriem; Destée, Alain; Lohmann, Ebba; Kabashi, Edor; Singleton, Andrew; Corti, Olga; Brice, Alexis

    2016-03-01

    Autosomal-recessive early-onset parkinsonism is clinically and genetically heterogeneous. The genetic causes of approximately 50% of autosomal-recessive early-onset forms of Parkinson disease (PD) remain to be elucidated. Homozygozity mapping and exome sequencing in 62 isolated individuals with early-onset parkinsonism and confirmed consanguinity followed by data mining in the exomes of 1,348 PD-affected individuals identified, in three isolated subjects, homozygous or compound heterozygous truncating mutations in vacuolar protein sorting 13C (VPS13C). VPS13C mutations are associated with a distinct form of early-onset parkinsonism characterized by rapid and severe disease progression and early cognitive decline; the pathological features were striking and reminiscent of diffuse Lewy body disease. In cell models, VPS13C partly localized to the outer membrane of mitochondria. Silencing of VPS13C was associated with lower mitochondrial membrane potential, mitochondrial fragmentation, increased respiration rates, exacerbated PINK1/Parkin-dependent mitophagy, and transcriptional upregulation of PARK2 in response to mitochondrial damage. This work suggests that loss of function of VPS13C is a cause of autosomal-recessive early-onset parkinsonism with a distinctive phenotype of rapid and severe progression. PMID:26942284

  10. Copeptin, a surrogate marker for vasopressin, is associated with kidney function decline in subjects with autosomal dominant polycystic kidney disease

    NARCIS (Netherlands)

    Boertien, Wendy E.; Meijer, Esther; Zittema, Debbie; van Dijk, Marjan A.; Rabelink, Ton J.; Breuning, Martijn H.; Struck, Joachim; Bakker, Stephan J. L.; Peters, Dorien J. M.; de Jong, Paul E.; Gansevoort, Ron T.

    2012-01-01

    The observational study by Boertin et al makes a valuable contribution to the research field of prevention and control of polycystic kidney disease, supports the assumption that copeptin is associated with disease severity in ADPKD and may have useful implications for the design of future clinical t

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  12. [18F-FDG PET/CT diagnosis of liver cyst infection in a patient with autosomal dominant polycystic kidney disease and fever of unknown origin].

    Science.gov (United States)

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

    2013-01-01

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

  13. An easy test but a hard decision: ethical issues concerning non-invasive prenatal testing for autosomal recessive disorders.

    Science.gov (United States)

    Skirton, Heather; Goldsmith, Lesley; Chitty, Lyn S

    2015-08-01

    Prenatal testing based on cell-free fetal DNA in maternal serum is now possible for specific monogenic conditions, and studies have shown that the use of non-invasive testing is supported by prospective parents and health professionals. However, some ethical issues have been raised concerning informed consent and paternal rights. The objective of this study was to explore ethical aspects of the use of non-invasive prenatal diagnostic testing for autosomal recessive disorders. We used a qualitative cross-sectional design, based on Thematic Analysis, and recruited 27 individuals of reproductive age who were carriers of one of four conditions: thalassaemia, sickle cell disease, cystic fibrosis or spinal muscular atrophy. Data were collected via focus groups or interviews. Participants were aware of the potential for such tests to be viewed as routine and suggested that obtaining written consent and allowing time for consideration is needed to facilitate autonomous choice and informed consent. All participants felt that mothers should be able to request such tests, but fathers who declined carrier testing should be made aware that fetal test results may reveal their status. We suggest that a written record of consent for non-invasive prenatal diagnosis should be used as a standard to help reinforce the serious nature of the test results. Where the father's carrier status could be revealed through fetal testing, he should be made aware of this before the results are available. Health professionals should discuss with the pregnant woman the best way to manage unsought information about the father's carrier status to minimise family disruption. PMID:25351779

  14. Genetic Linkage Analysis of 15 DFNB Loci in a Group of Iranian Families with Autosomal Recessive Hearing Loss

    Directory of Open Access Journals (Sweden)

    MA Tabatabaiefar

    2011-06-01

    Full Text Available "nBackground: Hearing loss (HL is the most frequent sensory birth defect in humans. Autosomal recessive non-syn­dromic HL (ARNSHL is the most common type of hereditary HL. It is extremely heterogeneous and over 70 loci (known as DFNB have been identified. This study was launched to determine the relative contribution of more frequent loci in a cohort of ARNSHL families."nMethods: Thirty-seven Iranian families including 36 ARNSHL families and 1 family with Pendred syndrome each with ≥ 4 affected individuals, from seven provinces of Iran, were ascertained. DFNB1 contribution was initially studied by DNA sequencing of GJB2 and linkage analysis using the relative STR markers. The excluded families were then sub­jected to homozygosity mapping for fifteen ARNSHL loci."nResults: Sixteen families were found to be linked to seven different known loci, including DFNB1 (6 families, DFNB4 (3 families +1 family with Pendred syndrome, DFNB63 (2 families, DFNB2 (1 family, DFNB7/11 (1 family, DFNB9 (1 family and DFNB21 (1 family. DNA sequencing of the corresponding genes is in progress to identify the pathogenic mu­tations. "nConclusion: The genetic causes were clarified in 43.2% of the studied families, giving an overview of the causes of ARNSHL in Iran. DFNB4 is ranked second after DFNB1 in the studied cohort. More genetic and epigenetic investiga­tions will have to be done to reveal the causes in the remaining families.   

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

    Science.gov (United States)

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

    2014-11-01

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

  16. [AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: HOW AND WHY SHOULD WE IDENTIFY THE PATIENTS "RAPIDLY PROGRESSING" TO END-STAGE RENAL DISEASE?].

    Science.gov (United States)

    Bodson, A; Meunier, P; Krzesinski, J-M; Jouret, F

    2016-04-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease characterised by the progressive development of multiple and bilateral cysts in kidneys and other organs. Most patients with ADPKD will develop, sooner or later, end-stage renal disease (ESRD). The morbidity and mortality associated with ESRD prompt physicians to identify early ADPKD patients considered as "rapid progressors", who have the greatest risk to rapidly develop ESRD. The rate of progression can be assessed by clinical--especially with the "predicting renal outcome in polycystic kidney disease score" (PROPKD-Score)-, biological (a decline of the glomerular filtration rate (GFR) of 4.4-5.9 ml/min/year and/or the doubling of serum creatinine within a 36-month period), or radiological criteria (total kidney volume (TKV) adjusted for the size > 600 cc/m and/or TKV annual growth rate > 5 %). Nowadays, there is no curative treatment for ADPKD. However, vasopressin-2 receptor antagonists, such as tolvaptan, appear to slow down the growth of renal cysts and the slope of GFR decline. The current management of ADPKD patients is mostly based on correcting the risk factors for progression, i.e. encouraging (over)-hydration, normalizing blood pressure, stimulating smoking cessation. PMID:27295898

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

    Science.gov (United States)

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

    2006-11-01

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

  18. Congenital sensorineural deafness in Australian stumpy-tail cattle dogs is an autosomal recessive trait that maps to CFA10.

    Directory of Open Access Journals (Sweden)

    Susan Sommerlad

    -value = 3.64, as was both coat colour and speckling. Fine mapping was then performed on 45 of these 50 dogs and a further 48 dogs (n = 93. Sequencing candidate gene Sox10 in 6 hearing ASCD, 2 unilaterally deaf ASCD and 2 bilaterally deaf ASCD did not reveal any disease-associated mutations. CONCLUSIONS: Deafness in ASCD is an incompletely penetrant autosomal recessive inherited disease that maps to CFA10.

  19. Skeletal Muscle, but not Cardiovascular Function, Is Altered in a Mouse Model of Autosomal Recessive Hypophosphatemic Rickets

    Science.gov (United States)

    Wacker, Michael J.; Touchberry, Chad D.; Silswal, Neerupma; Brotto, Leticia; Elmore, Chris J.; Bonewald, Lynda F.; Andresen, Jon; Brotto, Marco

    2016-01-01

    Autosomal recessive hypophosphatemic rickets (ARHR) is a heritable disorder characterized by hypophosphatemia, osteomalacia, and poor bone development. ARHR results from inactivating mutations in the DMP1 gene with the human phenotype being recapitulated in the Dmp1 null mouse model which displays elevated plasma fibroblast growth factor 23. While the bone phenotype has been well-characterized, it is not known what effects ARHR may also have on skeletal, cardiac, or vascular smooth muscle function, which is critical to understand in order to treat patients suffering from this condition. In this study, the extensor digitorum longus (EDL-fast-twitch muscle), soleus (SOL–slow-twitch muscle), heart, and aorta were removed from Dmp1 null mice and ex-vivo functional tests were simultaneously performed in collaboration by three different laboratories. Dmp1 null EDL and SOL muscles produced less force than wildtype muscles after normalization for physiological cross sectional area of the muscles. Both EDL and SOL muscles from Dmp1 null mice also produced less force after the addition of caffeine (which releases calcium from the sarcoplasmic reticulum) which may indicate problems in excitation contraction coupling in these mice. While the body weights of the Dmp1 null were smaller than wildtype, the heart weight to body weight ratio was higher. However, there were no differences in pathological hypertrophic gene expression compared to wildtype and maximal force of contraction was not different indicating that there may not be cardiac pathology under the tested conditions. We did observe a decrease in the rate of force development generated by cardiac muscle in the Dmp1 null which may be related to some of the deficits observed in skeletal muscle. There were no differences observed in aortic contractions induced by PGF2α or 5-HT or in endothelium-mediated acetylcholine-induced relaxations or endothelium-independent sodium nitroprusside-induced relaxations. In summary

  20. Skeletal muscle, but not cardiovascular function, is altered in a mouse model of autosomal recessive hypophosphatemic rickets

    Directory of Open Access Journals (Sweden)

    Michael J. Wacker

    2016-05-01

    Full Text Available Autosomal recessive hypophosphatemic rickets (ARHR is a heritable disorder characterized by hypophosphatemia, osteomalacia, and poor bone development. ARHR results from inactivating mutations in the DMP1 gene with the human phenotype being recapitulated in the Dmp1 null mouse model which displays elevated plasma fibroblast growth factor 23. While the bone phenotype has been well characterized, it is not known what effects ARHR may also have on skeletal, cardiac, or vascular smooth muscle function, which is critical to understand to treat patients suffering from this condition. In this study, the extensor digitorum longus (EDL- fast-twitch muscle, soleus (SOL- slow-twitch muscle, heart, and aorta were removed from Dmp1 null mice and ex-vivo functional tests were simultaneously performed in collaboration by three different laboratories. Dmp1 null EDL and SOL muscles produced less force than wildtype muscles after normalization for physiological cross sectional area of the muscles. Both EDL and SOL muscles from Dmp1 null mice also produced less force after the addition of caffeine (which releases calcium from the sarcoplasmic reticulum which may indicate problems in excitation contraction coupling in these mice. While the body weights of the Dmp1 null were smaller than wildtype, the heart weight to body weight ratio was higher. However, there were no differences in pathological hypertrophic gene expression compared to wildtype and maximal force of contraction was not different indicating that there may not be cardiac pathology under the tested conditions. We did observe a decrease in the rate of force development generated by cardiac muscle in the Dmp1 null which may be related to some of the deficits observed in skeletal muscle. There were no differences observed in aortic contractions induced by PGF2a or 5-HT or in endothelium-mediated acetylcholine-induced relaxations or endothelium-independent sodium nitroprusside-induced relaxations. In

  1. Skeletal Muscle, but not Cardiovascular Function, Is Altered in a Mouse Model of Autosomal Recessive Hypophosphatemic Rickets.

    Science.gov (United States)

    Wacker, Michael J; Touchberry, Chad D; Silswal, Neerupma; Brotto, Leticia; Elmore, Chris J; Bonewald, Lynda F; Andresen, Jon; Brotto, Marco

    2016-01-01

    Autosomal recessive hypophosphatemic rickets (ARHR) is a heritable disorder characterized by hypophosphatemia, osteomalacia, and poor bone development. ARHR results from inactivating mutations in the DMP1 gene with the human phenotype being recapitulated in the Dmp1 null mouse model which displays elevated plasma fibroblast growth factor 23. While the bone phenotype has been well-characterized, it is not known what effects ARHR may also have on skeletal, cardiac, or vascular smooth muscle function, which is critical to understand in order to treat patients suffering from this condition. In this study, the extensor digitorum longus (EDL-fast-twitch muscle), soleus (SOL-slow-twitch muscle), heart, and aorta were removed from Dmp1 null mice and ex-vivo functional tests were simultaneously performed in collaboration by three different laboratories. Dmp1 null EDL and SOL muscles produced less force than wildtype muscles after normalization for physiological cross sectional area of the muscles. Both EDL and SOL muscles from Dmp1 null mice also produced less force after the addition of caffeine (which releases calcium from the sarcoplasmic reticulum) which may indicate problems in excitation contraction coupling in these mice. While the body weights of the Dmp1 null were smaller than wildtype, the heart weight to body weight ratio was higher. However, there were no differences in pathological hypertrophic gene expression compared to wildtype and maximal force of contraction was not different indicating that there may not be cardiac pathology under the tested conditions. We did observe a decrease in the rate of force development generated by cardiac muscle in the Dmp1 null which may be related to some of the deficits observed in skeletal muscle. There were no differences observed in aortic contractions induced by PGF2α or 5-HT or in endothelium-mediated acetylcholine-induced relaxations or endothelium-independent sodium nitroprusside-induced relaxations. In summary, these

  2. Highly prevalent LIPH founder mutations causing autosomal recessive woolly hair/hypotrichosis in Japan and the genotype/phenotype correlations.

    Directory of Open Access Journals (Sweden)

    Kana Tanahashi

    Full Text Available Mutations in LIPH cause of autosomal recessive woolly hair/hypotrichosis (ARWH, and the 2 missense mutations c.736T>A (p.Cys246Ser and c.742C>A (p.His248Asn are considered prevalent founder mutations for ARWH in the Japanese population. To reveal genotype/phenotype correlations in ARWH cases in Japan and the haplotypes in 14 Japanese patients from 14 unrelated Japanese families. 13 patients had woolly hair, and 1 patient had complete baldness since birth. An LIPH mutation search revealed homozygous c.736T>A mutations in 10 of the patients. Compound heterozygous c.736T>A and c.742C>A mutations were found in 3 of the patients, and homozygous c.742C>A mutation in 1 patient. The phenotype of mild hypotrichosis with woolly hair was restricted to the patients with the homozygous c.736T>A mutation. The severe phenotype of complete baldness was seen in only 1 patient with homozygous c.742C>A. Haplotype analysis revealed that the alleles containing the LIPH c.736T>A mutation had a haplotype identical to that reported previously, although 4 alleles out of 5 chromosomes containing the LIPH c.742C>A mutation had a different haplotype from the previously reported founder allele. These alleles with c.742C>A are thought to be the third founder LIPH mutation causing ARWH. To accurately determine the prevalence of the founder mutations, we investigated allele frequencies of those mutations in 819 Japanese controls. Heterozygous c.736T>A mutations were found in 13 controls (allele frequency: 0.0079; carrier rate: 0.016, and heterozygous c.742C>A mutations were found in 2 controls (allele frequency: 0.0012; carrier rate: 0.0024. In conclusion, this study confirms the more accurate allele frequencies of the pathogenic founder mutations of LIPH and shows that there is a third founder mutation in Japan. In addition, the present findings suggest that the mutation patterns of LIPH might be associated with hypotrichosis severity in ARWH.

  3. Everolimus does not further reduce polycystic liver volume when added to long acting octreotide: Results from a randomized controlled trial

    NARCIS (Netherlands)

    Chrispijn, M.; Gevers, T.J.G.; Hol, J.C.; Monshouwer, R.; Dekker, H.M.; Drenth, J.P.H.

    2013-01-01

    BACKGROUND & AIMS: Polycystic liver disease (PLD) is associated with autosomal dominant polycystic kidney disease (ADPKD) or autosomal dominant polycystic liver disease (PCLD). The resulting hepatomegaly compromises quality of life. Somatostatin analogues reduce PLD volume by approximately 5% when g

  4. Cytochrome b558-negative, autosomal recessive chronic granulomatous disease: two new mutations in the cytochrome b558 light chain of the NADPH oxidase (p22-phox).

    OpenAIRE

    Boer, M.; Klein, A; Hossle, J P; Seger, R.; Corbeel, L; Weening, R S; Roos, D.

    1992-01-01

    Chronic granulomatous disease (CGD) is characterized by the failure of activated phagocytes to generate superoxide. Defects in at least four different genes lead to CGD. Patients with the X-linked form of CGD have mutations in the gene for the beta-subunit of cytochrome b558 (gp91-phox). Patients with a rare autosomal recessive form of CGD have mutations in the gene for the alpha-subunit of this cytochrome (p22-phox). Usually, this leads to the absence of cytochrome b558 in the phagocytes (A2...

  5. Structure of the Parkin in-between-ring domain provides insights for E3-ligase dysfunction in autosomal recessive Parkinson's disease

    OpenAIRE

    Beasley, Steven A; Hristova, Ventzislava A.; Shaw, Gary S.

    2007-01-01

    Mutations in Parkin are one of the predominant hereditary factors found in patients suffering from autosomal recessive juvenile Parkinsonism. Parkin is a member of the E3 ubiquitin ligase family that is defined by a tripartite RING1-in-between-ring (IBR)-RING2 motif. In Parkin, the IBR domain has been shown to augment binding of the E2 proteins UbcH7 and UbcH8, and the subsequent ubiquitination of the proteins synphilin-1, Sept5, and SIM2. To facilitate our understanding of Parkin function, t...

  6. The search for mutations in the gene for the beta subunit of the cGMP phosphodiesterase (PDEB) in patients with autosomal recessive retinitis pigmentosa

    DEFF Research Database (Denmark)

    Riess, O; Noerremoelle, A; Weber, B; Musarella, M A; Hayden, M R

    1992-01-01

    including 196 bp of the 5' region of the PDEB gene have been assessed for mutations by using single-strand conformational polymorphism analysis in 14 patients from 13 unrelated families with autosomal recessive retinitis pigmentosa (ARRP). No disease-causing mutations were found in this group of affected......The finding of a mutation in the beta subunit of the cyclic GMP (cGMP) phosphodiesterase gene causing retinal degeneration in mice (the Pdeb gene) prompted a search for disease-causing mutations in the human phosphodiesterase gene (PDEB gene) in patients with retinitis pigmentosa. All 22 exons...

  7. In vitro and in vivo characterization of histone deacetylase inhibitors as potential therapeutics for autosomal recessive proximal spinal muscular atrophy (SMA)

    OpenAIRE

    Rießland, Markus

    2009-01-01

    Spinal muscular atrophy is a common autosomal recessive neuromuscular disorder and the leading hereditary cause of death in early childhood. No cure is available. The disease determining gene for SMA is the survival motor neuron gene 1. SMN1 produces full length transcripts only, whereas the majority of transcripts derived from the copy gene SMN2 lack exon 7 due to alternative splicing. Although the amount of fully-functional SMN2-derived FL-SMN protein is not sufficient to overcome the absen...

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

    Directory of Open Access Journals (Sweden)

    Knight T

    2015-02-01

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

  9. A novel c.5308_5311delGAGA mutation in Senataxin in a Cypriot family with an autosomal recessive cerebellar ataxia

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    Zamba-Papanicolaou Eleni

    2008-04-01

    Full Text Available Abstract Background Senataxin (chromosome 9q34 was recently identified as the causative gene for an autosomal recessive form of Ataxia (ARCA, termed as Ataxia with Oculomotor Apraxia, type 2 (AOA2 and characterized by generalized incoordination, cerebellar atrophy, peripheral neuropathy, "oculomotor apraxia" and increased alpha-fetoprotein (AFP. Here, we report a novel Senataxin mutation in a Cypriot ARCA family. Methods We studied several Cypriot autosomal recessive cerebellar ataxia (ARCA families for linkage to known ARCA gene loci. We linked one family (909 to the SETX locus on chromosome 9q34 and screened the proband for mutations by direct sequencing. Results Sequence analysis revealed a novel c.5308_5311delGAGA mutation in exon 11 of the SETX gene. The mutation has not been detected in 204 control chromosomes from the Cypriot population, the remaining Cypriot ARCA families and 37 Cypriot sporadic cerebellar ataxia patients. Conclusion We identified a novel SETX homozygous c.5308_5311delGAGA mutation that co-segregates with ARCA with cerebellar atrophy and raised AFP.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-03-15

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

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

    International Nuclear Information System (INIS)

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

  12. Inhibitory action of chlorophyllin of autosome recessive lethals induced by irradiation; Accion inhibidora de la clorofilina de letales recesivos autosonicos inducidos por irradiacion

    Energy Technology Data Exchange (ETDEWEB)

    Salceda, V.M.; Pimentel, P.A.E.; Cruces, M.P. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)]. e-mail: vmss@nuclear.inin.mx

    2006-07-01

    The chlorolin is a sodium salt of the chlorophyll that has a strong protective action of the damage induced by different agents so much physical as chemical. In Drosophila there is reported this effect in somatic cells. In contrast, in germinal cells using tests with the sexual chromosomes has not been found such inhibitory action. For this reason, in this occasion we will refer to the effect of the lethality induced in autosome chromosomes, in particular to the chromosome II of this species. For such effect groups of males of the line Canton-S its were pre-treated for 24h with or without 69 mm of CCS and later on treaties with or without 40 Gy of gamma irradiation. The males were then subjected to the technical Cy L / Pm for the detection of recessive lethals. In the third generation the respective counts of the descendant of each one of them to determine the corresponding categories for each extracted chromosome were made. To be mendelian crosses it is expected for a normal chromosome a proportion 2:1 of individuals with genotype Cy L / +: +/+. The absence of individuals +/+ it is indicative of a lethal gene, until 10% of these individuals of each male's total descendant, it is considered that is carrying of a semi lethal gene. The sum of lethal and semi lethals constitutes the category detrimental. The obtained results indicated that the pre-treatment with CCS reduces in a significant way the frequency of induced lethals by 40 Gy of gamma rays. The fact that an effect inhibitor has not been observed in the test of recessive lethal bound to the sex obtained previously, it contrasts with the effect observed in the chromosome II, results of this study and with the one observed in the chromosome III in somatic cells. The above-mentioned shows a differential action of the CCS between sexual chromosomes and autosomal before the effect of the gamma radiation. At the moment we don't have an explanation to these evidences. To evaluate the action of the

  13. Autosomal Recessive Chronic Granulomatous Disease, IgA Deficiency and Refractory Autoimmune Thrombocytopenia Responding to Anti-CD20 Monoclonal Antibody

    Directory of Open Access Journals (Sweden)

    Shahin Shamsian Bibi

    2008-09-01

    Full Text Available Immunodeficiency and autoimmune disease may occur concomitantly in the same individual. Some of the immunodeficiency syndromes, especially humoral defects are associated with autoimmune disorders. Hematological manifestations such as thrombocytopenia and hemolytic anemia are the most common presentations. Persistent antigen stimulation due to an inherent defect in the ability of the immune system to eradicate pathogens is the primary cause leading to autoimmunity in patients with primary immunodeficiency states.We describe a 10 year old Iranian girl with chronic granulomatous disease -the autosomal recessive type with mutation of NCF1 gene P47- associated with selective IgA deficiency, refractory immune thrombocytopenia that showed an excellent response to Rituximab (Anti-CD20 monoclonal antibody.Patients with primary immunodeficiencies may have variable autoimmune manifestations. So for early detection and appropriate treatment, autoimmune diseases should always be suspected in such patients.

  14. Autosomal recessive spastic tetraplegia caused by AP4M1 and AP4B1 gene mutation: expansion of the facial and neuroimaging features.

    Science.gov (United States)

    Tüysüz, Beyhan; Bilguvar, Kaya; Koçer, Naci; Yalçınkaya, Cengiz; Çağlayan, Okay; Gül, Ece; Sahin, Sezgin; Çomu, Sinan; Günel, Murat

    2014-07-01

    Adaptor protein complex-4 (AP4) is a component of intracellular transportation of proteins, which is thought to have a unique role in neurons. Recently, mutations affecting all four subunits of AP4 (AP4M1, AP4E1, AP4S1, and AP4B1) have been found to cause similar autosomal recessive phenotype consisting of tetraplegic cerebral palsy and intellectual disability. The aim of this study was analyzing AP4 genes in three new families with this phenotype, and discussing their clinical findings with an emphasis on neuroimaging and facial features. Using homozygosity mapping followed by whole-exome sequencing, we identified two novel homozygous mutations in AP4M1 and a homozygous deletion in AP4B1 in three pairs of siblings. Spastic tetraplegia, microcephaly, severe intellectual disability, limited speech, and stereotypic laughter were common findings in our patients. All patients also had similar facial features consisting of coarse and hypotonic face, bitemporal narrowing, bulbous nose with broad nasal ridge, and short philtrum which were not described in patients with AP4M1 and AP4B1 mutations previously. The patients presented here and previously with AP4M1, AP4B1, and AP4E1 mutations shared brain abnormalities including asymmetrical ventriculomegaly, thin splenium of the corpus callosum, and reduced white matter volume. The patients also had hippocampal globoid formation and thin hippocampus. In conclusion, disorders due to mutations in AP4 complex have similar neurological, facial, and cranial imaging findings. Thus, these four genes encoding AP4 subunits should be screened in patients with autosomal recessive spastic tetraplegic cerebral palsy, severe intellectual disability, and stereotypic laughter, especially with the described facial and cranial MRI features. PMID:24700674

  15. A gene for autosomal recessive symmetrical spastic cerebral palsy maps to chromosome 2q24-25.

    OpenAIRE

    McHale, D P; Mitchell, S.; Bundey, S; Moynihan, L; Campbell, D. A.; Woods, C G; LENCH, N. J.; Mueller, R F; Markham, A F

    1999-01-01

    Cerebral palsy has an incidence of approximately 1/500 births, although this varies between different ethnic groups. Genetic forms of the disease account for approximately 1%-2% of cases in most countries but contribute a larger proportion in populations with extensive inbreeding. We have clinically characterized consanguineous families with multiple children affected by symmetrical spastic cerebral palsy, to locate recessive genes responsible for this condition. The eight families studied we...

  16. PPAR-γ agonists in polycystic kidney disease with frequent development of cardiovascular disorders.

    Science.gov (United States)

    Nagao, Shizuko; Yamaguchi, Tamio

    2012-06-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common of the monogenic disorders and is characterized by bilateral renal cysts; cysts in other organs including liver, pancreas, spleen, testis and ovary; vascular abnormalities including intracranial aneurysms and subarachnoid hemorrhage; and cardiac disorders such as left ventricular hypertrophy (LVH), mitral valve regurgitation, mitral valve prolapse and aortic regurgitation. Autosomal recessive polycystic kidney disease (ARPKD) is an early-onset multisystem disorder characterized by polycysts divided from the renal collecting ducts, congenital hepatic fibrosis, and ductal plate malformation complicated by pulmonary hyperplasia and systemic hypertension. In these polycystic kidney diseases (PKD), progressive enlargement of the cysts results from the aberrant proliferation of tubule epithelial cells and trans-epithelial fluid secretion leading to extensive nephron loss and interstitial fibrosis. Peroxisome proliferator-activated receptor-γ (PPAR-γ), a member of the ligand-dependent nuclear receptor superfamily, is expressed in a variety of tissues, including kidneys and liver, and plays important roles in cell proliferation, fibrosis, and inflammation. PPAR-γ agonists ameliorate polycystic kidney, polycystic liver and cardiac defects through β-catenin, c-Myc, CFTR, MCP-1, S6, ERK, and TGF-β signaling pathways in animal models of PKD. In this review, we describe the possible therapeutic value of PPAR-γ agonists in the treatment of renal and hepatic manifestations, and cardiac defects in progressive PKD. PMID:22122459

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

    Directory of Open Access Journals (Sweden)

    Annapareddy Shiva Nagendra Reddy

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-08-15

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

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

    International Nuclear Information System (INIS)

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

  20. PLEKHG5 deficiency leads to an intermediate form of autosomal-recessive Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Azzedine, Hamid; Zavadakova, Petra; Planté-Bordeneuve, Violaine; Vaz Pato, Maria; Pinto, Nuno; Bartesaghi, Luca; Zenker, Jennifer; Poirot, Olivier; Bernard-Marissal, Nathalie; Arnaud Gouttenoire, Estelle; Cartoni, Romain; Title, Alexandra; Venturini, Giulia; Médard, Jean-Jacques; Makowski, Edward; Schöls, Ludger; Claeys, Kristl G; Stendel, Claudia; Roos, Andreas; Weis, Joachim; Dubourg, Odile; Leal Loureiro, José; Stevanin, Giovanni; Said, Gérard; Amato, Anthony; Baraban, Jay; LeGuern, Eric; Senderek, Jan; Rivolta, Carlo; Chrast, Roman

    2013-10-15

    Charcot-Marie-Tooth disease (CMT) comprises a clinically and genetically heterogeneous group of peripheral neuropathies characterized by progressive distal muscle weakness and atrophy, foot deformities and distal sensory loss. Following the analysis of two consanguineous families affected by a medium to late-onset recessive form of intermediate CMT, we identified overlapping regions of homozygosity on chromosome 1p36 with a combined maximum LOD score of 5.4. Molecular investigation of the genes from this region allowed identification of two homozygous mutations in PLEKHG5 that produce premature stop codons and are predicted to result in functional null alleles. Analysis of Plekhg5 in the mouse revealed that this gene is expressed in neurons and glial cells of the peripheral nervous system, and that knockout mice display reduced nerve conduction velocities that are comparable with those of affected individuals from both families. Interestingly, a homozygous PLEKHG5 missense mutation was previously reported in a recessive form of severe childhood onset lower motor neuron disease (LMND) leading to loss of the ability to walk and need for respiratory assistance. Together, these observations indicate that different mutations in PLEKHG5 lead to clinically diverse outcomes (intermediate CMT or LMND) affecting the function of neurons and glial cells. PMID:23777631

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

    International Nuclear Information System (INIS)

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

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

    Institute of Scientific and Technical Information of China (English)

    薛澄; 梅长林

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Doroteya Raykova

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

  4. Autosomal-Recessive Mutations in the tRNA Splicing Endonuclease Subunit TSEN15 Cause Pontocerebellar Hypoplasia and Progressive Microcephaly.

    Science.gov (United States)

    Breuss, Martin W; Sultan, Tipu; James, Kiely N; Rosti, Rasim O; Scott, Eric; Musaev, Damir; Furia, Bansri; Reis, André; Sticht, Heinrich; Al-Owain, Mohammed; Alkuraya, Fowzan S; Reuter, Miriam S; Abou Jamra, Rami; Trotta, Christopher R; Gleeson, Joseph G

    2016-07-01

    The tRNA splicing endonuclease is a highly evolutionarily conserved protein complex, involved in the cleavage of intron-containing tRNAs. In human it consists of the catalytic subunits TSEN2 and TSEN34, as well as the non-catalytic TSEN54 and TSEN15. Recessive mutations in the corresponding genes of the first three are known to cause pontocerebellar hypoplasia (PCH) types 2A-C, 4, and 5. Here, we report three homozygous TSEN15 variants that cause a milder version of PCH2. The affected individuals showed progressive microcephaly, delayed developmental milestones, intellectual disability, and, in two out of four cases, epilepsy. None, however, displayed the central visual failure seen in PCH case subjects where other subunits of the TSEN are mutated, and only one was affected by the extensive motor defects that are typical in other forms of PCH2. The three amino acid substitutions impacted the protein level of TSEN15 and the stoichiometry of the interacting subunits in different ways, but all resulted in an almost complete loss of in vitro tRNA cleavage activity. Taken together, our results demonstrate that mutations in any known subunit of the TSEN complex can cause PCH and progressive microcephaly, emphasizing the importance of its function during brain development. PMID:27392077

  5. Validation of a clinical practice-based algorithm for the diagnosis of autosomal recessive cerebellar ataxias based on NGS identified cases.

    Science.gov (United States)

    Mallaret, Martial; Renaud, Mathilde; Redin, Claire; Drouot, Nathalie; Muller, Jean; Severac, Francois; Mandel, Jean Louis; Hamza, Wahiba; Benhassine, Traki; Ali-Pacha, Lamia; Tazir, Meriem; Durr, Alexandra; Monin, Marie-Lorraine; Mignot, Cyril; Charles, Perrine; Van Maldergem, Lionel; Chamard, Ludivine; Thauvin-Robinet, Christel; Laugel, Vincent; Burglen, Lydie; Calvas, Patrick; Fleury, Marie-Céline; Tranchant, Christine; Anheim, Mathieu; Koenig, Michel

    2016-07-01

    Establishing a molecular diagnosis of autosomal recessive cerebellar ataxias (ARCA) is challenging due to phenotype and genotype heterogeneity. We report the validation of a previously published clinical practice-based algorithm to diagnose ARCA. Two assessors performed a blind analysis to determine the most probable mutated gene based on comprehensive clinical and paraclinical data, without knowing the molecular diagnosis of 23 patients diagnosed by targeted capture of 57 ataxia genes and high-throughput sequencing coming from a 145 patients series. The correct gene was predicted in 61 and 78 % of the cases by the two assessors, respectively. There was a high inter-rater agreement [K = 0.85 (0.55-0.98) p < 0.001] confirming the algorithm's reproducibility. Phenotyping patients with proper clinical examination, imaging, biochemical investigations and nerve conduction studies remain crucial for the guidance of molecular analysis and to interpret next generation sequencing results. The proposed algorithm should be helpful for diagnosing ARCA in clinical practice. PMID:27142713

  6. Mutations in CDC14A, Encoding a Protein Phosphatase Involved in Hair Cell Ciliogenesis, Cause Autosomal-Recessive Severe to Profound Deafness.

    Science.gov (United States)

    Delmaghani, Sedigheh; Aghaie, Asadollah; Bouyacoub, Yosra; El Hachmi, Hala; Bonnet, Crystel; Riahi, Zied; Chardenoux, Sebastien; Perfettini, Isabelle; Hardelin, Jean-Pierre; Houmeida, Ahmed; Herbomel, Philippe; Petit, Christine

    2016-06-01

    By genetic linkage analysis in a large consanguineous Iranian family with eleven individuals affected by severe to profound congenital deafness, we were able to define a 2.8 Mb critical interval (at chromosome 1p21.2-1p21.1) for an autosomal-recessive nonsyndromic deafness locus (DFNB). Whole-exome sequencing allowed us to identify a CDC14A biallelic nonsense mutation, c.1126C>T (p.Arg376(∗)), which was present in the eight clinically affected individuals still alive. Subsequent screening of 115 unrelated individuals affected by severe or profound congenital deafness of unknown genetic cause led us to identify another CDC14A biallelic nonsense mutation, c.1015C>T (p.Arg339(∗)), in an individual originating from Mauritania. CDC14A encodes a protein tyrosine phosphatase. Immunofluorescence analysis of the protein distribution in the mouse inner ear showed a strong labeling of the hair cells' kinocilia. By using a morpholino strategy to knockdown cdc14a in zebrafish larvae, we found that the length of the kinocilia was reduced in inner-ear hair cells. Therefore, deafness caused by loss-of-function mutations in CDC14A probably arises from a morphogenetic defect of the auditory sensory cells' hair bundles, whose differentiation critically depends on the proper growth of their kinocilium. PMID:27259055

  7. A novel autosomal recessive non-syndromic hearing impairment locus (DFNB47) maps to chromosome 2p25.1-p24.3.

    Science.gov (United States)

    Hassan, Muhammad Jawad; Santos, Regie Lyn P; Rafiq, Muhammad Arshad; Chahrour, Maria H; Pham, Thanh L; Wajid, Muhammad; Hijab, Nadine; Wambangco, Michael; Lee, Kwanghyuk; Ansar, Muhammad; Yan, Kai; Ahmad, Wasim; Leal, Suzanne M

    2006-01-01

    Hereditary hearing impairment (HI) displays extensive genetic heterogeneity. Autosomal recessive (AR) forms of prelingual HI account for approximately 75% of cases with a genetic etiology. A novel AR non-syndromic HI locus (DFNB47) was mapped to chromosome 2p25.1-p24.3, in two distantly related Pakistani kindreds. Genome scan and fine mapping were carried out using microsatellite markers. Multipoint linkage analysis resulted in a maximum LOD score of 4.7 at markers D2S1400 and D2S262. The three-unit support interval was bounded by D2S330 and D2S131. The region of homozygosity was found within the three-unit support interval and flanked by markers D2S2952 and D2S131, which corresponds to 13.2 cM according to the Rutgers combined linkage-physical map. This region contains 5.3 Mb according to the sequence-based physical map. Three candidate genes, KCNF1, ID2 and ATP6V1C2 were sequenced, and were found to be negative for functional sequence variants. PMID:16261342

  8. The human intrinsic factor-vitamin B12 receptor, cubilin: molecular characterization and chromosomal mapping of the gene to 10p within the autosomal recessive megaloblastic anemia (MGA1) region

    DEFF Research Database (Denmark)

    Kozyraki, R; Kristiansen, M; Silahtaroglu, A;

    1998-01-01

    -5445 on the short arm of chromosome 10. This is within the autosomal recessive megaloblastic anemia (MGA1) 6-cM region harboring the unknown recessive-gene locus of juvenile megaloblastic anemia caused by intestinal malabsorption of cobalamin (Imerslund-Gräsbeck's disease). In conclusion, the present...... molecular and genetic information on human cubilin now provides circumstantial evidence that an impaired synthesis, processing, or ligand binding of cubilin is the molecular background of this hereditary form of megaloblastic anemia. Udgivelsesdato: 1998-May-15...

  9. Identification, by homozygosity mapping, of a novel locus for autosomal recessive congenital ichthyosis on chromosome 17p, and evidence for further genetic heterogeneity.

    Science.gov (United States)

    Krebsová, A; Küster, W; Lestringant, G G; Schulze, B; Hinz, B; Frossard, P M; Reis, A; Hennies, H C

    2001-07-01

    Autosomal recessive congenital ichthyosis (ARCI) comprises a group of severe disorders of keratinization, characterized by variable erythema and skin scaling. It is known for its high degree of genetic and clinical heterogeneity. Mutations in the gene for keratinocyte transglutaminase (TGM1) on chromosome 14q11 were shown in patients with ARCI, and a second locus was described, on chromosome 2q, in families from northern Africa. Three other loci for ARCI, on chromosomes 3p and 19p, were identified recently. We have embarked on a whole-genome scan for further loci for ARCI in four families from Germany, Turkey, and the United Arab Emirates. A novel ARCI locus was identified on chromosome 17p, between the markers at D17S938 and D17S1856, with a maximum LOD score of 3.38, at maximum recombination fraction 0.00, at D17S945, under heterogeneity. This locus is linked to the disease in the Turkish family and in the German family. Extensive genealogical studies revealed that the parents of the German patients with ARCI were eighth cousins. By homozygosity mapping, the localization of the gene could then be refined to the 8.4-cM interval between D17S938 and D17S1879. It could be shown, however, that ARCI in the two Arab families is linked neither to the new locus on chromosome 17p nor to one of the five loci known previously. Our findings give evidence of further genetic heterogeneity that is not linked to distinctive phenotypes. PMID:11398099

  10. The RIN2 syndrome: a new autosomal recessive connective tissue disorder caused by deficiency of Ras and Rab interactor 2 (RIN2).

    Science.gov (United States)

    Syx, Delfien; Malfait, Fransiska; Van Laer, Lut; Hellemans, Jan; Hermanns-Lê, Trinh; Willaert, Andy; Benmansour, Abdelmajid; De Paepe, Anne; Verloes, Alain

    2010-07-01

    Defects leading to impaired intracellular trafficking have recently been shown to play an important role in the pathogenesis of genodermatoses, such as the Ehlers-Danlos and the cutis laxa syndromes. A new genodermatosis, termed macrocephaly, alopecia, cutis laxa and scoliosis (MACS) syndrome has been described, resulting from a homozygous 1-bp deletion in RIN2. RIN2 encodes the Ras and Rab interactor 2, involved in the regulation of Rab5-mediated early endocytosis. We performed a clinical, ultrastructural and molecular study in a consanguineous Algerian family with three siblings affected by a distinctive autosomal recessive genodermatosis, reported in 2005 by Verloes et al. The most striking clinical features include progressive facial coarsening, gingival hypertrophy, severe scoliosis, sparse hair and skin and joint hyperlaxity. Ultrastructural studies of the skin revealed important abnormalities in the collagen fibril morphology, and fibroblasts exhibited a dilated endoplasmic reticulum and an abnormal Golgi apparatus with rarefied and dilated cisternae. Molecular analysis of RIN2 revealed a novel homozygous 2-bp deletion in all affected individuals. The c.1914_1915delGC mutation introduces a frameshift and creates a premature termination codon, leading to nonsense-mediated mRNA decay. These findings confirm that RIN2 defects are associated with a distinct genodermatosis and underscore the involvement of RIN2 and its associated pathways in the pathogenesis of connective tissue disorders. The current family displays considerable phenotypic overlap with MACS syndrome. However, our family shows a dermatological and ultrastructural phenotype belonging to the Ehlers-Danlos rather than the cutis laxa spectrum. Therefore, the MACS acronym is not entirely appropriate for the current family. PMID:20424861

  11. Prevalence and range of GJB2 and SLC26A4 mutations in patients with autosomal recessive non‑syndromic hearing loss.

    Science.gov (United States)

    Jiang, Hua; Chen, Jia; Shan, Xin-Ji; Li, Ying; He, Jian-Guo; Yang, Bei-Bei

    2014-07-01

    The frequency and distribution of genetic mutations that cause deafness differ significantly according to ethnic group and region. Zhejiang is a province in the southeast of China, with an exceptional racial composition of the population caused by mass migration in ancient China. The purpose of the present study was to investigate the prevalence and spectrum of gap junction‑β2 (GJB2), solute carrier family 26 (anion exchanger) member 4 (SLC26A4) and GJB3 mutations in patients with autosomal recessive non‑syndromic hearing loss (ARNHL) in this area. A total of 176 unrelated pediatric patients with ARNHL were enrolled in the study. A genomic DNA sample was extracted from the peripheral blood. Polymerase chain reaction was employed, and the products were sequenced to screen for mutations in GJB2. In addition, a SNaPshot sequencing method was utilized to detect four hotspot mutations in SLC26A4 (IVS7‑2A>G and c.2168A>G) and GJB3 (c.538C>T and c.547G>A). All patients were subjected to a temporal bone computed tomography scan to identify enlarged vestibular aqueducts (EVA). In total, 14 different mutations, including two new mutations (p.W44L and p.D66N) of GJB2, were detected. The most common pathogenic mutation of GJB2 was c.235delC (15.1%), followed by c.176_191del16 (1.7%), c.299_300delAT (1.7%), c.508_511dup (0.85%) and c.35delG (0.28%) of the total alleles. Mutation analysis of SLC26A4 demonstrated that 13.6% (24/176) of patients carried at least one mutant allele. The patients with EVA (84.2%) had SLC26A4 mutations, and 31% had homozygous mutations. Only one patient carried a heterozygous mutation of GJB3 (c.538C>T). Compared with the other regions of China, in the present population cohort, the prevalence and spectrum of mutations in GJB2 was unique, and in patients with EVA the frequency of a homozygous mutation in SLC26A4 was significantly lower. These findings may be of benefit in genetic counseling and risk assessment for families from this area of

  12. Al-Aqeel Sewairi Syndrome, a new autosomal recessive disorder with multicentric osteolysis, nodulosis and arthropathy. The first genetic defect of matrix metalloproteinase 2 gene

    International Nuclear Information System (INIS)

    We report a distinctive autosomal recessive multicentric osteolysis in Saudi Arabian families with distal arthropathy of the metacarpal, metatarsal and interphalangeal joints, with ultimate progression to the proximal joints with decreased range of movements and deformities with ankylosis and generalized osteopenia. In addition, they had large, painful to touch palmar and plantar pads. Hirsutism and mild dysmorphic facial features including proptosis, a narrow nasal bridge, bulbous nose and micrognathia. Using a genome-wide search for microsatellite markers from 11 members of the family from the Armed Forces Hospital and King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia, localized the disease gene to chromosome 16q12-21. Haplotype analysis with additional markers narrowed the critical region to 1.2cM and identified the matrix metalloproteinase 2 (MMP-2), (gelatinase A, collagenase type IV, EC 3.4, 24,24) gene as a disease candidate at Mount Sinai School of Medicine, New York, United States of America in April 2000. Some affected individuals were homoallelic for a nonsense mutation (TCA>TAA) in codon 244 of exon 5, predicting the replacement of a tyrosine residue by a stop codon in the first fibronectin type II domain (Y244X). Other affected members had a missense mutation in exon 2 arginine 101-histidine (R101H) leading to no MMP-2 enzyme activity in serum or fibroblast or both of affected individuals. In other affected members, a non-pathogenic homoallelic GT transversion resulted in the substitution of an aspartate with a tyrosine residue in codon 210 of exon 4 (D210Y). The MMP-2-null mouse has no developmental defects, but are small, which may reflect genetic redundancy. The discovery that deficiency of this well-characterized gelatinase/collagenase results in an inherited form of an osteolytic and arthritic disorder provides an invaluable insights for the understanding of osteolysis and arthritis and is the first genetic

  13. Do consanguineous parents of a child affected by an autosomal recessive disease have more DNA identical-by-descent than similarly-related parents with healthy offspring? Design of a case-control study

    Directory of Open Access Journals (Sweden)

    Cornel Martina C

    2010-07-01

    Full Text Available Abstract Background The offspring of consanguineous relations have an increased risk of congenital/genetic disorders and early mortality. Consanguineous couples and their offspring account for approximately 10% of the global population. The increased risk for congenital/genetic disorders is most marked for autosomal recessive disorders and depends on the degree of relatedness of the parents. For children of first cousins the increased risk is 2-4%. For individual couples, however, the extra risk can vary from zero to 25% or higher, with only a minority of these couples having an increased risk of at least 25%. It is currently not possible to differentiate between high-and low-risk couples. The quantity of DNA identical-by-descent between couples with the same degree of relatedness shows a remarkable variation. Here we hypothesize that consanguineous partners with children affected by an autosomal recessive disease have more DNA identical-by-descent than similarly-related partners who have only healthy children. The aim of the study is thus to establish whether the amount of DNA identical-by-descent in consanguineous parents of children with an autosomal recessive disease is indeed different from its proportion in consanguineous parents who have healthy children only. Methods/Design This project is designed as a case-control study. Cases are defined as consanguineous couples with one or more children with an autosomal recessive disorder and controls as consanguineous couples with at least three healthy children and no affected child. We aim to include 100 case couples and 100 control couples. Control couples are matched by restricting the search to the same family, clan or ethnic origin as the case couple. Genome-wide SNP arrays will be used to test our hypothesis. Discussion This study contains a new approach to risk assessment in consanguineous couples. There is no previous study on the amount of DNA identical-by-descent in consanguineous

  14. A comparison of ultrasound and magnetic resonance imaging shows kidney length predicts chronic kidney disease in autosomal dominant polycystic kidney disease

    OpenAIRE

    Bhutani, Harpreet; Smith, Vikram; Rahbari-Oskoui, Frederic; Mittal, Ankush; Grantham, Jared J.; Torres, Vicente E.; Mrug, Michal; Bae, Kyongtae T.; Wu, Zhiyuan; Ge, Yinghui; Landslittel, Doug; Gibbs, Patrice; O’Neill, W. Charles; Arlene B Chapman; ,

    2015-01-01

    ADPKD is marked by gradual renal cyst and kidney enlargement and ultimately renal failure. Magnetic resonance-based, height-adjusted total kidney volume (htTKV) over 600 ml/m predicts the development of CKD Stage 3 within 8 years in the Consortium for Radiologic Imaging in Polycystic Kidney Disease cohort. Here we compared simultaneous ultrasound and magnetic resonance imaging to determine if ultrasound and kidney length (KL) predict future CKD Stage 3 over longer periods of follow-up. A tota...

  15. Addressing key issues in the consanguinity-related risk of autosomal recessive disorders in consanguineous communities: lessons from a qualitative study of British Pakistanis.

    Science.gov (United States)

    Darr, A; Small, N; Ahmad, W I U; Atkin, K; Corry, P; Modell, B

    2016-01-01

    Currently, there is no consensus regarding services required to help families with consanguineous marriages manage their increased genetic reproductive risk. Genetic services for communities with a preference for consanguineous marriage in the UK remain patchy, often poor. Receiving two disparate explanations of the cause of recessive disorders (cousin marriage and recessive inheritance) leads to confusion among families. Further, the realisation that couples in non-consanguineous relationships have affected children leads to mistrust of professional advice. British Pakistani families at-risk for recessive disorders lack an understanding of recessive disorders and their inheritance. Such an understanding is empowering and can be shared within the extended family to enable informed choice. In a three-site qualitative study of British Pakistanis, we explored family and health professional perspectives on recessively inherited conditions. Our findings suggest, firstly, that family networks hold strong potential for cascading genetic information, making the adoption of a family-centred approach an efficient strategy for this community. However, this is dependent on provision of high-quality and timely information from health care providers. Secondly, families' experience was of ill-coordinated and time-starved services, with few having access to specialist provision from Regional Genetics Services; these perspectives were consistent with health professionals' views of services. Thirdly, we confirm previous findings that genetic information is difficult to communicate and comprehend, further complicated by the need to communicate the relationship between cousin marriage and recessive disorders. A communication tool we developed and piloted is described and offered as a useful resource for communicating complex genetic information. PMID:26363620

  16. Identification and functional characterization of a genetic defect in the kinetochore protein BOD1 associated with autosomal recessive mental retardation and oligomenorrhea

    OpenAIRE

    Esmaeeli-Nieh, Sahar

    2011-01-01

    Im Zuge unserer klinischen und molekularen Studien zur Identifizierung der genetischen Ursachen autosomal-rezessiver geistiger Behinderung, untersuchten wir eine iranische Familie mit vier Patientinnen, welche einen milden bis mittelschweren Grad geistiger Behinderung sowie Oligomenorrhoe aufweisen. Mittels Autozygosity Mapping wurde ein 4,3 Mbp Intervall auf Chromosom 5 identifiziert, welches 28 Gene beinhaltet. Die kodierenden Bereiche dieser Gene wurden sequenziert und als einzige Nukleoti...

  17. Microcefalia primária autossômica recessiva em três famílias pernambucanas: aspectos clínicos e moleculares Autosomal recessive primary microcephaly in three families from Pernambuco: clinical and molecular aspects

    Directory of Open Access Journals (Sweden)

    Gabriela F. Leal

    2005-06-01

    Full Text Available OBJETIVOS: descrever os aspectos clínicos de três famílias pernambucanas com microcefalia primária autossômica recessiva e as análises de ligação em uma delas (família 2. MÉTODOS: três famílias consangüíneas pernambucanas, não relacionadas biologicamente, com microcefalia primária, foram estudadas. Os heredogramas e a história clínica dos afetados foram construídos com base em informações obtidas de seus pais e outros parentes. O exame físico foi realizado em todos os afetados, seus genitores e na quase totalidade dos irmãos normais dos afetados. O DNA genômico dos afetados da família 2 e de seus pais foi usado em reações de PCR (polimerase chain reaction com primers elaborados para amplificar marcadores microssatélites ligados aos locos já conhecidos de microcefalia primária autossômica recessiva. Os marcadores amplificados foram submetidos a eletroforese e seus alelos analisados. RESULTADOS: nas três famílias, os afetados apresentavam perímetro cefálico muito reduzido acompanhado de retardo mental e apenas uma paciente (da família 3 manifestava outras alterações neurológicas, mas sem dismorfias associadas. Estudos moleculares demonstraram que a microcefalia, na família 2, não apresentava ligação com nenhum dos locos associados à microcefalia primária autossômica recessiva já conhecidos. CONCLUSÕES: pelo menos mais um gene associado à microcefalia primária autossômica recessiva existe e aguarda identificação.OBJECTIVES: to describe the clinical findings in three families from Pernambuco with autosomal recessive primary microcephaly, and the linkage analysis in one of them (family 2. METHODS: three consanguineous families from Pernambuco, not related one to another and with primary microcephaly, were studied. The genealogical data and the clinical history of the affected individuals were obtained from their parents and other family members. All the affected subjects, almost all their normal

  18. Confirmation of the 2p locus for the mild autosomal recessive lim-girdle muscular dystrophy gene (LGMD2B) in three families allows refinement of the candidate region

    Energy Technology Data Exchange (ETDEWEB)

    Bashir, R.; Iughetti, P.; Strachan, T. [Univ. of Newcastle upon Tyne (United Kingdom)] [and others

    1995-05-01

    The mild autosomal recessive limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of muscle diseases. The first gene to be mapped and associated with this phenotype was a locus on 15q geographic isolate. These results have been confirmed in other populations, but it was shown that there is genetic heterogeneity for this form of LGMD. Recently, a second locus has been mapped to chromosome 2p. The confirmation of the mapping of this second locus in LGMD families from different populations is of utmost importance for the positional cloning of this gene (HGMW-approved symbol LGMD2B). In this publication, haplotypes generated from five chromosome 2 markers from all of the known large families linked to chromosome 2p are reported together with the recombinants that show the current most likely location of the LGMD 2B gene. 9 refs., 2 figs., 1 tab.

  19. 家族性高胆固醇血症亚型--隐性遗传性高胆固醇血症研究进展%The subtype of familial hypercholesterolemia--the progression of autosomal recessive hypercholesterolemia

    Institute of Scientific and Technical Information of China (English)

    马斐斐; 王绿娅

    2006-01-01

    家族性高胆固醇血症(familial hypercholesterolemia,FH;MIM 143890)是一种常染色体显性遗传性疾病,是脂质代谢疾病中最严重的一种,导致早期发生较为严重的冠心病(coronary artery disease,CAD).FH存在一些亚型,其中常染色体隐性遗传性高胆固醇血症(autosomal recessive hypercholesterolemia,ARH;MIM 603813)纯合患者,可表现为胆固醇水平异常升高、皮肤肌腱黄色瘤和早发的冠心病,临床表现与FH极为相似.

  20. Deficient T Cell Receptor Excision Circles (TRECs) in autosomal recessive hyper IgE syndrome caused by DOCK8 mutation: implications for pathogenesis and potential detection by newborn screening.

    Science.gov (United States)

    Dasouki, Majed; Okonkwo, Kingsley C; Ray, Abhishek; Folmsbeel, Caspian K; Gozales, Diana; Keles, Sevgi; Puck, Jennifer M; Chatila, Talal

    2011-11-01

    Loss of function of DOCK8 is the major cause of autosomal recessive hyper IgE syndrome, a primary immunodeficiency with adaptive and innate immune dysfunction. Patients affected with ARHIES have atopic dermatitis and recurrent, potentially life-threatening viral and bacterial infections. Three consanguineous Pakistani siblings presented with severe atopic dermatitis and superinfection. Direct sequencing of DOCK8 in all three affected siblings demonstrated homozygosity for a deleterious, novel exon 14 frame shift mutation. Current newborn screening for severe combined immunodeficiency syndrome (SCID) and related T cell disorders relies on the quantitation of T Cell Receptor Excision Cells (TRECs) in dried blood spots (DBS). Significantly, both older affected siblings had undetectable TRECs, and TREC copy number was reduced in the youngest sibling. These findings suggest that AR-HIES may be detected by TREC newborn screening, and this diagnosis should be considered in the evaluation of newborns with abnormal TRECs who do not have typical SCID. PMID:21763205

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-11-01

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

  3. Congenital hepatic fibrosis in the Franches-Montagnes horse is associated with the polycystic kidney and hepatic disease 1 (PKHD1 gene.

    Directory of Open Access Journals (Sweden)

    Michaela Drögemüller

    Full Text Available Congenital hepatic fibrosis has been described as a lethal disease with monogenic autosomal recessive inheritance in the Swiss Franches-Montagnes horse breed. We performed a genome-wide association study with 5 cases and 12 controls and detected an association on chromosome 20. Subsequent homozygosity mapping defined a critical interval of 952 kb harboring 10 annotated genes and loci including the polycystic kidney and hepatic disease 1 (autosomal recessive gene (PKHD1. PKHD1 represents an excellent functional candidate as variants in this gene were identified in human patients with autosomal recessive polycystic kidney and hepatic disease (ARPKD as well as several mouse and rat mutants. Whereas most pathogenic PKHD1 variants lead to polycystic defects in kidney and liver, a small subset of the human ARPKD patients have only liver symptoms, similar to our horses with congenital hepatic fibrosis. The PKHD1 gene is one of the largest genes in the genome with multiple alternative transcripts that have not yet been fully characterized. We sequenced the genomes of an affected foal and 46 control horses to establish a comprehensive list of variants in the critical interval. We identified two missense variants in the PKHD1 gene which were strongly, but not perfectly associated with congenital hepatic fibrosis. We speculate that reduced penetrance and/or potential epistatic interactions with hypothetical modifier genes may explain the imperfect association of the detected PKHD1 variants. Our data thus indicate that horses with congenital hepatic fibrosis represent an interesting large animal model for the liver-restricted subtype of human ARPKD.

  4. 早发型帕金森病DJ-1基因突变的分析%THE MUTATIONAL ANALYSIS OF DJ-1 GENE IN PATIENTS WITH AUTOSOMAL RECESSIVE EARLY-ONSET PARKINSON'S DISEASE

    Institute of Scientific and Technical Information of China (English)

    袁志刚; 罗曙光; 窦霄云; 华荣; 谭建强; 胡启平; 马军; 方玲; 舒伟

    2009-01-01

    目的:分析广西地区早发型帕金森病(Parkinsion's disease,PD)患者及常染色体隐性遗传早发型帕金森病(autosomal recessive early-onset Parkinsion's disease,AREP)家系患者DJ-1基因外显子的突变特点,探讨DJ-1基因外显子的突变与广西地区PD关系.方法:应用聚合酶链式反应(PCR)、单链构象多态性(SSCP)及DNA测序等技术查找DJ-1基因缺失突变及点突变.结果:45例早发型散发性PD患者和12例分别来自5个常染色体隐性遗传早发型PD家系的DJ-1基因的2~7号外显子全部被成功扩增,未见大片段缺失.产物经SSCP方法和测序检测,未见点突变与缺失突变.结论:DJ-1基因的突变不是广西地区早发型PD患者的发病的危险因素.

  5. Exome sequencing identifies a founder frameshift mutation in an alternative exon of USH1C as the cause of autosomal recessive retinitis pigmentosa with late-onset hearing loss.

    Directory of Open Access Journals (Sweden)

    Samer Khateb

    Full Text Available We used a combined approach of homozygosity mapping and whole exome sequencing (WES to search for the genetic cause of autosomal recessive retinitis pigmentosa (arRP in families of Yemenite Jewish origin. Homozygosity mapping of two arRP Yemenite Jewish families revealed a few homozygous regions. A subsequent WES analysis of the two index cases revealed a shared homozygous novel nucleotide deletion (c.1220delG leading to a frameshift (p.Gly407Glufs*56 in an alternative exon (#15 of USH1C. Screening of additional Yemenite Jewish patients revealed a total of 16 homozygous RP patients (with a carrier frequency of 0.008 in controls. Funduscopic and electroretinography findings were within the spectrum of typical RP. While other USH1C mutations usually cause Usher type I (including RP, vestibular dysfunction and congenital deafness, audiometric screening of 10 patients who are homozygous for c.1220delG revealed that patients under 40 years of age had normal hearing while older patients showed mild to severe high tone sensorineural hearing loss. This is the first report of a mutation in a known USH1 gene that causes late onset rather than congenital sensorineural hearing loss. The c.1220delG mutation of USH1C accounts for 23% of RP among Yemenite Jewish patients in our cohort.

  6. Rationale for early treatment of polycystic kidney disease.

    Science.gov (United States)

    Grantham, Jared J

    2015-07-01

    In hereditary cystic disorders, renal injury begins with the formation of the first cyst. Renal injury may manifest as large kidneys, abdominal pain, hypertension and hematuria in children and young adults with autosomal dominant polycystic kidney disease (ADPKD). In autosomal recessive PKD (ARPKD) and ADPKD, cysts form primarily in collecting ducts and expand progressively. Collecting duct cysts that block urine flow have the potential to block urine formation in large numbers of upstream nephrons. In an ARPKD rat congenitally lacking vasopressin, only a few cysts developed until exogenous arginine vasopressin (AVP) was administered. AVP elevates cyclic AMP in vulnerable tubule cells to stimulate mitogenesis and fluid secretion, thereby causing cysts to form and enlarge indefinitely. The administration of an AVP-V2 receptor inhibitor or the consumption of sufficient water to persistently lower plasma AVP levels will ameliorate disease progression. Renal volume measurements provide the most reliable way to forecast long-term outcome in individual children and adult patients with ADPKD. Many drugs that have demonstrated efficacy in small clinical trials, preclinical trials and cell-based studies are in the treatment pipeline. Counseling, regular exercise, limitation of dietary calories, salt, protein and fat, increased fluid intake throughout the day and treatment of hypertension are components of a rational treatment program that can be offered at an early age to those with, or at risk for developing PKD. PMID:25022529

  7. Familial megacalyces with autosomal recessive inheritance

    International Nuclear Information System (INIS)

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

  8. Genetics Home Reference: autosomal recessive primary microcephaly

    Science.gov (United States)

    ... are the most common cause of the disorder, accounting for about half of all cases. The genes ... 7 ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific articles on PubMed (1 link) PubMed OMIM (7 links) ...

  9. Autosomal-dominant osteopetrosis: An incidental finding

    Directory of Open Access Journals (Sweden)

    Rajathi Maria

    2010-01-01

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

  10. Mutation analysis of genes associated with autosomal recessive in early-onset parkinsonism%常染色体隐性遗传早发性帕金森综合征致病基因的突变分析

    Institute of Scientific and Technical Information of China (English)

    严新翔; 曹立; 沈璐; 江泓; 赵国华; 唐北沙; 张玉虎; 郭纪锋; 李静; 夏昆; 蔡芳; 潘乾; 龙志高; 陈涛

    2005-01-01

    目的研究常染色体隐性遗传早发性帕金森综合征(autosomal recessive early-onset parkinsonism,AREP)parkin、PINK1及DJ-1基因的突变.方法应用聚合酶链反应、DNA直接测序和限制性核酸内切酶酶切等技术对15个AREP家系进行parkin、PINK1及DJ-1基因的突变分析.结果在3个家系中发现parkin基因3个杂合突变,分别为202-203delAG和新发现的1069-1074delGTGTCC与T1422C突变.在2个家系中发现2个新的PINK1基因突变,分别为C938T及C1474T.未见DJ-1基因突变.3个PARK2家系平均发病年龄(25.2±5.7)岁,临床上肌张力障碍、姿势不稳、腱反射活跃、症状晨轻暮重常见,对多巴制剂反应好,左旋多巴诱导的运动障碍常见;2个PARK6家系平均发病年龄(25.8±10.0)岁,临床特征与PARK2相似,但未见肌张力障碍、姿势不稳及左旋多巴诱导的运动障碍.结论 parkin、PINK1基因突变是AREP的常见病因;DJ-1在我国AREP中可能罕见;PARK2和PARK6具有相似临床表现,但均具有临床异质性.

  11. Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy: parallels with Stiff-Person Syndrome and other movement disorders

    Directory of Open Access Journals (Sweden)

    Woods C Geoffrey

    2004-11-01

    Full Text Available Abstract Background Cerebral palsy (CP is an heterogeneous group of neurological disorders of movement and/or posture, with an estimated incidence of 1 in 1000 live births. Non-progressive forms of symmetrical, spastic CP have been identified, which show a Mendelian autosomal recessive pattern of inheritance. We recently described the mapping of a recessive spastic CP locus to a 5 cM chromosomal region located at 2q24-31.1, in rare consanguineous families. Methods Here we present data that refine this locus to a 0.5 cM region, flanked by the microsatellite markers D2S2345 and D2S326. The minimal region contains the candidate gene GAD1, which encodes a glutamate decarboxylase isoform (GAD67, involved in conversion of the amino acid and excitatory neurotransmitter glutamate to the inhibitory neurotransmitter γ-aminobutyric acid (GABA. Results A novel amino acid mis-sense mutation in GAD67 was detected, which segregated with CP in affected individuals. Conclusions This result is interesting because auto-antibodies to GAD67 and the more widely studied GAD65 homologue encoded by the GAD2 gene, are described in patients with Stiff-Person Syndrome (SPS, epilepsy, cerebellar ataxia and Batten disease. Further investigation seems merited of the possibility that variation in the GAD1 sequence, potentially affecting glutamate/GABA ratios, may underlie this form of spastic CP, given the presence of anti-GAD antibodies in SPS and the recognised excitotoxicity of glutamate in various contexts. Table 4 GAD1 single nucleotide substitutions detected on mutation analysis and occurring in sequences submitted to NCBI SNP database and in the literature. This is not a definitive list, but includes those described at the time of the mutational analysis. *Nucleotide positions were not provided by Maestrini et al. [47]. Source SNP position in mRNA, from the translational start site (bp Gene position of SNP(bp Amino acid change (ALappalainen et al. (2002 A(-478Del Exon

  12. [Polycystic kidney disease: from genetics to dialysis].

    Science.gov (United States)

    Ortiz Arduan, Alberto

    2012-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of end stage renal disease. In addition, end-stage renal disease is complicated by acquired polycystic kidney disease. Recent advances in our understanding of the pathogenesis of ADPKD have identified the primary cilium as key to cystogenesis, and have defined the molecular, cellular and tissue pathogenesis of the disease, leading to the design of clinical trials that may ultimately lead to effective therapy of the disease. In 2012 a key trial has shown that blockade of vasopressin receptors with tolvaptan slows the rate of cyst growth and may slow the loss of renal function. PMID:24298871

  13. Complete staghorn calculus in polycystic kidney disease: infection is still the cause

    OpenAIRE

    Mao, Zhiguo; Xu, Jing; YE, CHAOYANG; Chen, Dongping; Mei, Changlin

    2013-01-01

    Background Kidney stones in patients with autosomal dominant polycystic kidney disease are common, regarded as the consequence of the combination of anatomic abnormality and metabolic risk factors. However, complete staghorn calculus is rare in polycystic kidney disease and predicts a gloomy prognosis of kidney. For general population, recent data showed metabolic factors were the dominant causes for staghorn calculus, but for polycystic kidney disease patients, the cause for staghorn calculu...

  14. Reducing Polycystic Liver Volume in ADPKD: Effects of Somatostatin Analogue Octreotide

    OpenAIRE

    Caroli, Anna; Antiga, Luca; Cafaro, Mariateresa; Fasolini, Giorgio; Remuzzi, Andrea; Remuzzi, Giuseppe; Ruggenenti, Piero

    2010-01-01

    Background and objectives: No medical treatment is available for polycystic liver disease, a frequent manifestation of autosomal-dominant polycystic kidney disease (ADPKD). In a prospective, randomized, double-blind, crossover study, 6 months of octreotide (40 mg every 28 days) therapy limited kidney volume growth more effectively than placebo in 12 patients with ADPKD.

  15. Polycystic kidney disease gene in the Lewis polycystic kidney rat is mapped to chromosome 10q21–q26

    Directory of Open Access Journals (Sweden)

    Yengkopiong JP

    2012-08-01

    Full Text Available Jada Pasquale YengkopiongDr John Garang Memorial University of Science and Technology, Faculty of Science and Technology, Bor, Republic of South SudanBackground: Polycystic kidney disease (PKD is a life-threatening disorder that affects the kidneys of millions of people across the world. The disease is normally inherited, but it can also be acquired, and leads to development of many cysts in the renal nephrons. In this study, the aim was to characterize PKD in the Lewis polycystic kidney (LPK rat, the newest model for human PKD.Methods: Mating experiments were performed between male LPK rats with PKD and female Brown Norway and Wistar Kyoto rats without PKD to raise second filial (F2 and backcross 1 (BC1 progeny, respectively. Rats that developed PKD were identified. Histological examination of the kidneys and liver was performed. Liver tissue samples were collected from each rat and used to extract DNA. The extracted DNA was amplified, and mapping and linkage analyses were performed to identify the quantitative trait locus that controlled the disease phenotypes.Results: It was established that the disease was controlled by a recessive mutation in a single gene (F2: PKD = 42, non-PKD = 110, χ2 = 0.53; BC1: PKD = 67, non-PKD = 72, χ2 = 0.18, P > 0.05 and that the disease was inherited as autosomal recessive polycystic kidney disease (ARPKD. The rats with PKD developed larger fluid-filled cystic kidneys, higher systolic blood pressure, and anemia. However, there were no extrarenal cysts and no pup deaths. Mapping studies and linkage analyses associated the disease phenotypes in both the F2 and BC1 rats to chromosome 10q21–q26, giving a maximum LOD score of 7.9 (P = 0.00001 between peak markers D10Rat180 and D10Rat26.Conclusion: The quantitative trait locus on chromosome 10q21–q26 does not contain the Pkhd-1 gene, and it is different from quantitative trait loci that control ARPKD in other murine models. The candidate genes located in the

  16. Detection of PKD1 mutations in autosomal dominant polycystic kidney disease by Ion Torrent semiconductor sequencing%应用Ion Torrent半导体测序技术检测常染色体显性多囊肾患者PKD1基因致病突变

    Institute of Scientific and Technical Information of China (English)

    马定远; 胡平; 罗春玉; 张菁菁; 成建; 王玉国; 蒋涛; 许争峰

    2015-01-01

    目的 基于Ion Torrent半导体测序技术建立常染色体显性多囊肾患者PKD1基因致病突变检测方法并评价其临床应用价值.方法 遗传病分子诊断.收集2013年7月至2014年8月在南京市妇幼保健院就诊的多囊肾患者5例,提取外周血DNA,采用9个长链PCR反应特异性扩增PKD1基因全部编码区,PCR产物混合后进行酶切,经模板制备、乳液PCR和磁珠颗粒富集,应用Ion Torrent个体化基因组测序仪进行PKD1基因测序,对发现的致病突变通过Sanger测序验证.结果 应用Ion Torrent半导体测序技术检测到4例患者存在PKD1基因致病突变,分别为外显子12微小缺失突变(c.2966_2970delCGGCG),外显子15微小缺失突变(c.5014_5015delAG),内含子23剪接位点突变(c.8972-2A> G),外显子36错义突变(c.10675G> A).结论 基于长链PCR技术和Ion Torrent 半导体测序技术,建立了常染色体显性多囊肾病基因诊断方法,该方法能够特异性检测PKD1基因致病突变,具有较高的临床应用价值.%Objective To develop and validate a method for detectiug PKD1 mutations in autosomal dominant polycystic kidney disease by Ion Torrent semiconductor sequencing.Methods Molecular diagnosis of genetic diseases.Five Chinese patients with polycystic kidney disease were recruited frown Nanjing Maternity and Child Health Care Hospital for genetic counseling from July 2013 to August 2014.Peripheral blood samples were collected for DNA analysis.The entire PKD1 coding region was amplified by nine long-range PCR reactions.Pooled amplicons from individual patients were sheared to short fragments using fragmentase.After template preparation,emulsion PCR,and ion sphere particles enrichment,the barcoded libraries were subsequently sequenced using the Ion Torrent sequencer.Candidate variants were validated by Sanger sequencing.Results By using the targeted Ion Torrent sequencing method,four PKD1 mutations were identified from 4 patients,including c.2966

  17. Diagnosing recessions

    OpenAIRE

    Òscar Jordà

    2010-01-01

    The beginnings and ends of recessions are officially dated about 12 months after the fact. A common rule of thumb declares recessions as two quarters of consecutive negative GDP growth, but this is very inaccurate. A better option is to apply medical diagnostic evaluation methods to the business conditions indexes of the Chicago and Philadelphia Federal Reserve Banks, which suggests the recent recession ended sometime between June and August 2009.

  18. Polycystic kidney disease: The cadence of kidney growth in ADPKD.

    Science.gov (United States)

    Chapman, Arlene

    2009-06-01

    Autosomal-dominant polycystic kidney disease is characterized by the development and expansion of cysts, which ultimately results in kidney failure. The rate of this expansion can now be quantified within a short period of time, which has implications for assessing the risk of renal failure in affected patients. PMID:19474826

  19. Long-term rapamycin therapy in the Han:SPRD rat model of polycystic kidney disease (PKD)

    OpenAIRE

    Zafar, Iram; Belibi, Franck A; He, Zhibin; Edelstein, Charles L

    2009-01-01

    Background. Short-term studies have demonstrated that rapamycin or everolimus treatment decreases cyst formation and improves renal function in animal models of polycystic kidney disease (PKD). Autosomal dominant polycystic kidney disease (ADPKD) patients would likely require life-long treatment with rapamycin.

  20. Aneurisma gigante do segmento intracavernoso da carótida interna associado a doença renal policística autossômica dominante: relato de caso Giant aneurysm of the intracavernous internal carotid artery associated with autosomal dominant polycystic kidney disease: case report

    Directory of Open Access Journals (Sweden)

    Keven F. Ponte

    2006-09-01

    Full Text Available Apresenta-se o caso de mulher de 60 anos com doença renal policística autossômica dominante (DRPAD que desenvolveu quadro de cefaléia e oftalmoplegia completa à direita. A TC levantou a hipótese de um aneurisma gigante do segmento intracavernoso da carótida interna direita, o que foi confirmado pela arteriografia. Realizou-se, então, tratamento endovascular por oclusão do vaso parental com molas destacáveis no segmento supraclinóideo. A paciente evoluiu com a interrupção da cefaléia e com redução parcial da ptose e da oftalmoplegia. Neste artigo, enfatiza-se a relação entre DRPAD e aneurismas intracranianos. Comenta-se a história natural dos aneurismas originados no segmento intracavernoso da artéria carótida interna e comparam-se as opções terapêuticas no manejo destas lesões.We report the case of a 60 years-old woman with autosomal dominant polycystic kidney disease (ADPKD that presented with headache and right complete ophthalmoplegia. The CT scan raised the possibility of a giant aneurysm of the right intracavernous internal carotid artery, confirmed by angiography. The patient underwent endovascular occlusion of parent vessel with detachable coils, then she presented interruption of headache and partial recovery of ptosis and ophthalmoplegia. We emphasize the relationship between ADPKD and intracranial aneurysms. We also discuss the natural history and compare the therapeutic options for the management of giant aneurysms of the cavernous portion of the carotid artery.

  1. Huge bilateral polycystic kidneys with suspicion of malignancy, recurrent bleeding in cysts, and acute abdomen

    OpenAIRE

    Bhatty, TAN; Moazin, MS; Haque, R.

    2012-01-01

    We present a case of huge bilateral polycystic kidneys, with suspicion of malignancy and repeated admissions with acute abdomen, secondary to bleeding in cysts, and anaemia, requiring affected side nephrectomy. Key message Autosomal dominant polycystic kidney disease (ADPKD) mostly ends up with end stage renal disease (ESRD), requiring haemodialysis, with increased risk of malignancy and enlargement of kidneys with its associated complications, mostly dealt with conservatively, except maligna...

  2. UNUSUAL CASE OF POLYCYSTIC LIVER DISEASE

    OpenAIRE

    Andreea Brumaru; Catalina Mihai; Cristina Cijevschi Prelipcean

    2005-01-01

    Polycystic liver disease (PCLD) is a rare disease defined as the presence of four or more thin-walled cyst within the hepatic parenchyma.The most common form of autosomal dominant PCLD coexist with renal cystic disease. In contrast to the concomitant renal and liver cystic disease, the isolated form of PCLD is a comparatively rare form, that displays no renal involvement.Only 7% of patients with PCDL do not have associated renal cyst. Most cases are asymptomatic. Patients generally have pre...

  3. Mutations in PDGFRB Cause Autosomal-Dominant Infantile Myofibromatosis

    OpenAIRE

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

    2013-01-01

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

  4. Recession Rebound

    Science.gov (United States)

    Weinstein, Margery

    2011-01-01

    A return to normal after a crisis is a good thing. Who doesn't want back what once seemed lost? The problem is it usually isn't a simple task figuring out how to patch together a scaled-back training program. When the recession hit in fall 2008, trainers were asked to scale down programming and make do with fewer resources. With a recovery in full…

  5. TH gene mutation in Chinese patients with autosomal recessive dopa-responsive dystonia%中国人常染色体隐性遗传性多巴反应性肌张力障碍TH基因突变分析

    Institute of Scientific and Technical Information of China (English)

    刘威; 唐北沙; 曹贵方; 陈涛; 李海燕

    2004-01-01

    目的研究中国人常染色体隐性遗传性(autosomal recessive,AR)多巴反应性肌张力障碍(dopa-responsive dystonia, DRD)患者酪氨酸羟化酶(tyrosine hydroxylase,TH)基因的突变特点.方法应用聚合酶链反应-单链构象多态性技术和DNA序列分析方法对5个AR-DRD家系的先证者和两例散发DRD患者进行TH基因突变分析. 结果 TH基因第1~2、5~11、13~14外显子的扩增产物未见异常电泳条带,DNA直接测序TH基因的第3、4、12外显子,结果未发现异常.结论 TH基因在中国人AR-DRD家系中突变率不高,提示我国AR-DRD患者具有遗传异质性,可能存在新的致病基因.

  6. Mutation analysis of DJ1 gene in patients with autosomal recessive early- onset Parkinsonism%常染色体隐性遗传性早发型帕金森综合征DJ1基因突变研究

    Institute of Scientific and Technical Information of China (English)

    郭纪锋; 严新翔; 曹立; 唐北沙; 张玉虎; 夏昆; 蔡芳; 潘乾; 沈璐; 江泓; 赵国华

    2005-01-01

    目的探讨常染色体隐性遗传性早发型帕金森综合征(autosomal recessive early-onset Parkinsonism,AR-EP)DJ1基因的突变特点.方法应用聚合酶链反应结合DNA直接序列分析方法,对11个常染色体隐性遗传性早发型帕金森综合征家系先证者的DJ1基因进行突变研究.结果本组AR-EP患者未发现DJ1基因的致病突变,在内含子区发现6个多态,分别为IVS1-15T→C、IVS4+30T→G、IVS4+45G→A、IVS4+46G→A、IVS5+31G→A和g.168-185del,其中3个(IVS1-15T→C、IVS4+45G→A、IVS4+46C→A)为新发现的多态.结论中国人常染色体隐性遗传性早发型帕金森综合征患者DJ1基因突变可能罕见.

  7. 三个常染色体隐性遗传早发型帕金森病家系的PARKIN基因研究%A study on PARKIN gene in three pedigrees with autosomal recessive early-onset Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    金淼; 焦劲松; 顾卫红; 王康; 邹海强; 陈彪; 王国相

    2005-01-01

    目的探讨PARKIN基因与中国人常染色体隐性遗传早发型帕金森病(autosomal recessive early-onset Parkinson's disease, AREP)家系的关系.方法对3个AREP家系的6例患者和23位成员进行系统的临床检查并进行PARKIN基因PCR扩增,产物通过变性高压液相色谱(denaturing high-performance liquid chromatography, DHPLC)进行突变检测,阳性结果标本进行基因测序.结果所有研究对象的PARKIN基因外显子均扩增成功.DHPLC检测和基因测序发现一个家系中存在PARKIN基因杂合Gly284Arg突变,另一个家系中存在PARKIN基因Ser167Asn多态性,且患者均有环境毒物接触史.结论 PARKIN基因杂合Gly284Arg突变在环境因素的协同作用下可能导致发病.PARKIN基因Ser167Asn多态性是帕金森病的易感因素,汞中毒与其共同作用可能导致发病.

  8. Urine Kidney Injury Molecule-1 can Predict the Progression of Autosomal Dominant Polycystic Kidney Disease in Early Stage Patients%尿肾损伤分子-1预示常染色体显性多囊肾病早期发展速度

    Institute of Scientific and Technical Information of China (English)

    马熠熠; 陈冬平; 梅长林; 郁胜强; 李林; 徐成钢

    2011-01-01

    目的:探讨尿KIM-1水平与早期ADPKD患者病情进展的相关性,及其预示作用.方法:(1)收集临床确诊为ADPKD患者(CKD1,2期)及体检健康人群各40例,并取其晨起后第2次尿液标本,采用ELISA方法测定尿液中Kim-1浓度,比较多囊肾病人群与正常人群在Kim-1表达程度的差异;(2)用多囊肾患者肾脏体积增长速度判断疾病进展状况,用MRI肾脏成像的方法计算6个月间隔后肾脏体积增长情况;(3)去除肾脏总体积大于1 500 cm3的患者,以肾脏体积半年增长率2.7%为界,将患者划分为高平均速度组和低平均速度组,比较两组间KIM-1水平差异.结果:(1)多囊肾患者与正常人群相比,eGFR水平(采用CKD-EPI公式计算)差异无统计学意义(P>0.05),但尿中Kim-1水平多囊肾病组显著升高[(837.9±821.5) pg/ml vs (440.3±270.2) pg/ml,P<0.05];(2)多囊肾患者半年肾脏体积增长速度为(4.88±3.86)%,显著高于国外报道的多囊肾患者半年体积增长速度;(3)高平均速度组KIM-1水平高于低平均速度组(P<0.05).结论:Kim-1作为肾小管损伤后出现的一种重要的生物标记物在多囊肾病患者群中表达显著升高,能预示早期肾脏体积并未发展到一定程度的多囊肾患者肾体积的增长快慢,但Kim-1在疾病进展中的作用机制仍需要进一步的实验研究阐明.%Objective:To study the correlation between urine Kidney injury molecule - 1( KIM - 1 ) and the progression of Autosomal Dominant Polycystic Kidney Disease ( ADPKD ) in early stage patients.Methods :( 1 )Human KIM - 1 Elisa kit was used to determine the different levels of urine KIM - 1 in 40 ADPKD patients and 40 healthy individuals.All the patients were diagnosed with stage Ⅰ or stage Ⅱ chronic kidney disease at the time of enrollment.( 2 )We used the increasing rate of total kidney volume to evaluate the progression of ADPKD patients.Increases in kidney volume in ADPKD patients were detected within 6 months by

  9. Gastrocnemius recession.

    Science.gov (United States)

    Anderson, John G; Bohay, Donald R; Eller, Erik B; Witt, Bryan L

    2014-12-01

    The Grand Rapids Arch Collapse classifications create a novel system for categorizing and correlating numerous common foot and ankle conditions related to a falling arch. The algorithm for treating these conditions is exceptionally replicable and has excellent outcomes. Gastrocnemius equinus diagnosis plays a crucial role in the pathology of arch collapse. A contracture of the gastrocnemius muscle is increasingly recognized as the cause of several foot and ankle conditions. The authors have expanded their indications for gastrocnemius recession to include arch pain without radiographic abnormality, calcaneus apophysitis, plantar fasciitis/fibromas, Achilles tendonosis, early-onset diabetic Charcot arthropathy, and neuropathic forefoot ulcers. PMID:25456721

  10. Pain determinants of pain in autosomal dominant polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    José Luiz Nishiura

    2013-09-01

    Full Text Available Pain is the most common symptom reported by ADPKD patients, afflicting approximately 60% of cases and may result from renal hemorrhage, calculi, urinary tract infections, cyst rupture, or due to stretching of the capsule or traction of the renal pedicle. We have recently investigated pain patterns in AD-PKD patients using a translated version of a pain questionnaire specific for AD-PKD population. The questionnaire revealed that 67% patients with ADPKD exhibited some type of pain. The findings of that study emphasized that pain appeared early in the course of ADPKD, when patients still exhibited preserved renal function. In the present study, a multivariate logistic regression analysis disclosed that renal volume (9-fold increased risk and nephrolithiasis (4-fold increased risk were the most important determinant factors for pain in ADPKD patients with preserved renal function, after adjustments for the presence of hypertension and duration of the disease.

  11. Clinical spectrum of early onset cerebellar ataxia with retained tendon reflexes: an autosomal recessive ataxia not to be missed Espectro clínico da ataxia cerebelar de início precoce com reflexos mantidos: uma ataxia autossômica recessiva para não ser esquecida

    Directory of Open Access Journals (Sweden)

    José Luiz Pedroso

    2013-06-01

    Full Text Available Autosomal recessive cerebellar ataxias are a heterogeneous group of neurological disorders. In 1981, a neurological entity comprised by early onset progressive cerebellar ataxia, dysarthria, pyramidal weakness of the limbs and retained or increased upper limb reflexes and knee jerks was described. This disorder is known as early onset cerebellar ataxia with retained tendon reflexes. In this article, we aimed to call attention for the diagnosis of early onset cerebellar ataxia with retained tendon reflexes as the second most common cause of autosomal recessive cerebellar ataxias, after Friedreich ataxia, and also to perform a clinical spectrum study of this syndrome. In this data, 12 patients from different families met all clinical features for early onset cerebellar ataxia with retained tendon reflexes. Dysarthria and cerebellar atrophy were the most common features in our sample. It is uncertain, however, whether early onset cerebellar ataxia with retained tendon reflexes is a homogeneous disease or a group of phenotypically similar syndromes represented by different genetic entities. Further molecular studies are required to provide definitive answers to the questions that remain regarding early onset cerebellar ataxia with retained tendon reflexes.As ataxias cerebelares autossômicas recessivas são um grupo heterogêneo de doenças neurológicas. Em 1981, foi descrita uma entidade neurológica incluindo ataxia cerebelar progressiva de início precoce, disartria, liberação piramidal e manutenção ou aumento dos reflexos tendíneos nos membros superiores e inferiores. Essa síndrome é conhecida como ataxia cerebelar de início precoce com reflexos mantidos. Neste artigo, o objetivo foi chamar a atenção para o diagnóstico de ataxia cerebelar de início precoce com reflexos mantidos como a segunda causa mais comum de ataxia cerebelar autossômica recessiva, após a ataxia de Friedreich, e também realizar um estudo do espectro cl

  12. DJ-1 gene rearrangement mutation in patients with autosomal recessive early-onset parkinsonism using real-time PCR%应用实时荧光定量PCR技术检测常染色体隐性遗传性早发型帕金森综合征的DJ-1基因外显子重排突变

    Institute of Scientific and Technical Information of China (English)

    张海南; 肖彬; 聂利珞; 郭纪锋; 王春喻; 王磊; 何丹; 严新翔; 唐北沙

    2010-01-01

    目的:建立应用实时荧光定量PCR技术(real-time polymerase chain reaction,real-time PCR)检测DJ-1基因外显子重排突变的技术平台,并应用该技术对常染色体隐性遗传性早发型帕金森综合征(autosomal recessive early-onset Parkinsonism, AREP)DJ-1基因进行外显子重排突变分析.方法:应用实时荧光定量PCR分析方法,对22个AREP家系先证者和30个正常对照的DJ-1基因进行外显子重排突变分析.结果:本研究中获得了扩增效率和特异性均满意的DJ-1基因各编码外显子实时荧光定量PCR反应条件及各外显子引物;本组AREP患者未发现DJ-1基因的外显子重排突变.结论:建立了应用实时荧光定量PCR技术进行DJ-1基因外显子重排突变检测的技术平台;中国人群AREP患者DJ-1基因外显子重排突变可能罕见.

  13. Pathogenic sequence for dissecting aneurysm formation in a hypomorphic polycystic kidney disease 1 mouse model

    NARCIS (Netherlands)

    Hassane, S.; Claij, N.; Lantinga-van Leeuwen, I.S.; Munsteren, J.C. van; Lent, N. van; Hanemaaijer, R.; Breuning, M.H.; Peters, D.J.M.; Ruiter, M.C. de

    2007-01-01

    OBJECTIVE - Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a multi-system disorder characterized by progressive cyst formation in the kidneys. Serious complications of ADPKD are intracranial and aortic aneurysms. The condition is mainly caused by mutations in the PKD1 or PKD2 gene. We have

  14. Polycystic kidney disease in four British shorthair cats with successful treatment of bacterial cyst infection.

    Science.gov (United States)

    Nivy, R; Lyons, L A; Aroch, I; Segev, G

    2015-09-01

    Polycystic kidney disease is the most common inherited disorder in cats. Renal cysts progressively increase in size and number, resulting in a gradual decrease in kidney function. An autosomal dominant mutation in exon 29 of the polycystin-1 gene has been identified, mostly in Persian and Persian-related breeds. This case study describes polycystic kidney disease in four British shorthair cats, of which two had the same genetic mutation reported in Persian and Persian-related cats. This likely reflects introduction of this mutation into the British shorthair breeding line because of previous outcrossing with Persian cats. An infected renal cyst was diagnosed and successfully treated in one of the cats. This is a commonly reported complication in human polycystic kidney disease, and to the authors' knowledge has not previously been reported in cats with polycystic kidney disease. PMID:25677715

  15. ADAM17 promotes proliferation of collecting duct kidney epithelial cells through ERK activation and increased glycolysis in polycystic kidney disease.

    Science.gov (United States)

    Beck Gooz, Monika; Maldonado, Eduardo N; Dang, Yujing; Amria, May Y; Higashiyama, Shigeki; Abboud, Hanna E; Lemasters, John J; Bell, P Darwin

    2014-09-01

    Polycystic kidney disease (PKD) is a common genetic disorder leading to cyst formation in the kidneys and other organs that ultimately results in kidney failure and death. Currently, there is no therapy for slowing down or stopping the progression of PKD. In this study, we identified the disintegrin metalloenzyme 17 (ADAM17) as a key regulator of cell proliferation in kidney tissues of conditional knockout Ift88(-/-) mice and collecting duct epithelial cells from Ift88°(rpk) mice, animal models of autosomal recessive polycystic kidney disease (ARPKD). Using Western blotting, an enzyme activity assay, and a growth factor-shedding assay in the presence or absence of the specific ADAM17 inhibitor TMI-005, we show that increased expression and activation of ADAM17 in the cystic kidney and in collecting duct epithelial cells originating from the Ift88°(rpk) mice (designated as PKD cells) lead to constitutive shedding of several growth factors, including heparin-binding EGF-like growth factor (HB-EGF), amphiregulin, and transforming growth factor-α (TGF-α). Increased growth factor shedding induces activation of the EGFR/MAPK/ERK pathway and maintains higher cell proliferation rate in PKD cells compared with control cells. PKD cells also displayed increased lactate formation and extracellular acidification indicative of aerobic glycolysis (Warburg effect), which was blocked by ADAM17 inhibition. We propose that ADAM17 is a key promoter of cellular proliferation in PKD cells by activating the EGFR/ERK axis and a proproliferative glycolytic phenotype. PMID:24899059

  16. Genetics Home Reference: autosomal recessive congenital stationary night blindness

    Science.gov (United States)

    ... Genet. 2012 Feb 10;90(2):321-30. doi: 10.1016/j.ajhg.2011.12.007. Erratum ... Hum Genet. 2009 Nov;85(5):720-9. doi: 10.1016/j.ajhg.2009.10.013. Epub ... Hum Genet. 2009 Nov;85(5):711-9. doi: 10.1016/j.ajhg.2009.10.003. Epub ...

  17. Genetics Home Reference: autosomal recessive axonal neuropathy with neuromyotonia

    Science.gov (United States)

    ... neuromyotonia is a disorder that affects the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles ... caused by damage to a particular part of peripheral nerves called axons , which are the extensions of nerve ...

  18. Autosomal recessive hypoparathyroidism with renal insufficiency and developmental delay.

    OpenAIRE

    Shaw, N J; Haigh, D; Lealmann, G T; Karbani, G.; Brocklebank, J. T.; Dillon, M J

    1991-01-01

    Four children (two boys and two girls) with hypoparathyroidism, renal insufficiency, and developmental delay are described. They were the products of consanguineous marriages in three related Asian families presenting over a six year period. All the children died within the first 15 months of life despite treatment. Postmortem examination on one child showed absent parathyroid glands. We believe these children represent a previously undescribed syndrome that appears to be inherited in an auto...

  19. Renal-hepatic-pancreatic dysplasia: an autosomal recessive malformation.

    OpenAIRE

    Torra, R.; Alós, L.; Ramos, J.; Estivill, X

    1996-01-01

    We report two brothers with a cystic malformation of the kidneys, liver, and pancreas. In both cases the malformation was fatal and the children died shortly after birth. The pathological findings, consisting of multicystic dysplastic kidneys, dilated and dysgenetic bile ducts, dilated pancreatic ducts, and polysplenia, correspond to those reported by Ivemark as renal-hepatic-pancreatic dysplasia. Many polymalformation syndromes include cystic affectation of these three organs, so this syndro...

  20. Autosomal recessive limb girdle myasthenia in two sisters.

    Directory of Open Access Journals (Sweden)

    Shankar A

    2002-10-01

    Full Text Available Limb girdle myasthenic syndromes are rare genetic disorders described under the broad heterogeneous group known as congenital myasthenic syndromes and present with mixed features of myasthenia and myopathy. The familial limb girdle myasthenia has been described as one with selective weakness of pectoral and pelvic girdles, showing a positive response to edrophonium chloride. A report of two sisters affected by this disorder is presented.

  1. TMPRSS3 mutations in autosomal recessive nonsyndromic hearing loss.

    Science.gov (United States)

    Battelino, Saba; Klancar, Gasper; Kovac, Jernej; Battelino, Tadej; Trebusak Podkrajsek, Katarina

    2016-05-01

    Nonsyndromic genetic deafness is highly heterogeneous in its clinical presentation, pattern of inheritance and underlying genetic causes. Mutations in TMPRSS3 gene encoding transmembrane serine protease account for Slovenia resulting in uniform phenotype with profound congenital hearing loss, and satisfactory hearing and speech recognition outcome after cochlear implantation. Consequently, TMPRSS3 gene analysis should be included in the first tier of genetic investigations of ARNSHL along with GJB2 and GJB6 genes. PMID:26036852

  2. Genetics Home Reference: autosomal recessive hyper-IgE syndrome

    Science.gov (United States)

    ... with AR-HIES have neurological problems, such as paralysis that affects the face or one side of the body (hemiplegia). Blockage of blood flow in the brain or abnormal bleeding in the brain, both of ...

  3. Sepiapterin reductase deficiency an autosomal recessive DOPA-responsive dystonia

    NARCIS (Netherlands)

    N.G. Abeling; M. Duran; H.D. Bakker; L. Stroomer; B. Thony; N. Blau; J. Booij; B.T. Poll-The

    2006-01-01

    The diagnosis of a 14-year-old girl with a new homoallelic mutation in the sepiapterin reductase (SR) gene is reported. Initially she presented at the age of 2 with hypotonia and mild cognitive developmental delay, and was diagnosed as having mild methylmalonic aciduria, which was recently identifie

  4. Autosomal recessive, early-onset Parkinson’s disease

    NARCIS (Netherlands)

    V. Bonifati (Vincenzo)

    2003-01-01

    textabstractParkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease, with a prevalence of 1-2% in the population aged 65 years.1 The disease is clinically defi ned by the presence of parkinsonism (the combination of akinesia, resting tremor, and muscul

  5. Autosomal recessive, early-onset Parkinson’s disease

    OpenAIRE

    Bonifati, Vincenzo

    2003-01-01

    textabstractParkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease, with a prevalence of 1-2% in the population aged 65 years.1 The disease is clinically defi ned by the presence of parkinsonism (the combination of akinesia, resting tremor, and muscular rigidity), and a good response to dopaminergic therapy. These features are associated at pathological level with neuronal loss and gliosis, mainly in the substantia nigra pars compacta but also ...

  6. Severe generalized recessive dystrophic epidermolysis bullosa (Hallopeau-Siemen's) - a case report

    OpenAIRE

    Hassan, Iffat; Keen, Mohammad Abid

    2013-01-01

    Dystrophic epidermolysis bullosa is a rare heterogenous group of genetic disorders that is clinically characterized by increased skin fragility, blister formation, followed by scarring of skin and mucus membranes, either spontaneously or after induction of minor trauma. It can either be inherited as an autosomal recessive or autosomal dominant form. We herein report a case of severe generalized recessive dystrophic epidermolysis bullosa in a 6 year old ethnic Kashmiri girl.

  7. Polycystic ovarian syndrome

    OpenAIRE

    Nina Madnani; Kaleem Khan; Phulrenu Chauhan; Girish Parmar

    2013-01-01

    Polycystic ovarian syndrome (PCOS) is a "multispeciality" disorder suspected in patients with irregular menses and clinical signs of hyperandrogenism such as acne, seborrhoea, hirsutism, irregular menses, infertility, and alopecia. Recently, PCOS has been associated with the metabolic syndrome. Patients may develop obesity, insulin resistance, acanthosis nigricans, Type 2 diabetes, dyslipidemias, hypertension, non-alcoholic liver disease, and obstructive sleep apnoea. Good clinical examinatio...

  8. A retrospective study on management of gross hematuria in autosomal dominant polycystic kidney disease patients%常染色体显性多囊肾病患者并发肉眼血尿治疗方法的回顾研究

    Institute of Scientific and Technical Information of China (English)

    马熠熠; 陈冬平; 梅长林; 郁胜强; 戎殳; 张彤; 李林

    2012-01-01

    目的 寻找治疗常染色体显性多囊肾病(ADPKD)并发肉眼血尿的理想疗法.方法 1993年以来曾在我科住院治疗以及目前在我科多囊肾病专科门诊定期就诊随访的ADPKD患者为对象.收集ADPKD患者出现肉眼血尿时的平均年龄、性别构成、肾功能水平、诱发因素、治疗方案、症状持续时间、血小板计数、凝血参数、肾脏囊肿大小等资料,分别以不同的肉眼血尿诱发因素及治疗方案进行分组,比较其各指标间的差异.结果 共筛选出ADPKD患者905例.279例(男150例,女129例)曾有肉眼血尿病史,其中146例能提供完整的病史和治疗经过,而只有101例能提供相关的实验室检查结果.在这101例中,肉眼血尿可出现在慢性肾脏病(CKD)任何一期;GFR为(56.4±44.1)ml·min-1·(1.73 m2)-1;症状持续时间(8.8±8.0)d;男、女患者症状持续时间差异无统计学意义[(8.2±7.3)d比(9.5±8.8)d,P=0.426);凝血参数均在正常参考范围内,其中91例患者血小板计数正常.不同诱发因素导致的肉眼血尿持续时间差异有统计学意义(P<0.05).卧床休息组症状持续时间显著短于其他组患者(P<0.05).各组间血小板计数、凝血酶时间和国际标准化比值等差异无统计学意义.结论 对出现肉眼血尿的ADPKD患者应首先明确其诱因.卧床休息应作为核心治疗措施.在考虑使用止血药物时建议使用抗纤维蛋白溶解类药物,不需要预防性使用抗生索.%Objective To seauch the ideal management for gross hematuria in autosomal dominant polycystic kidney disease (ADPKD).Methods ADPKD patients who were ever hospitalized and followed up in our department since 1993 were enrolled in the study.Demographic and clinical data were colloected,such as gender,age of gross hematuria,level of renal function,causative factors,management strategies,duration of gross hematuria,blood platelet count,activated partial thromboplastin time,prothrombin time

  9. Yersinia pseudotuberculosis aortitis in a patient with diverticulosis and polycystic kidney disease.

    Science.gov (United States)

    McCloskey, Sarah; Haslam, Philip; Price, David A; Sayer, John A

    2015-04-01

    An 81-year-old gentleman with chronic kidney disease presented with pyrexia and a new systolic cardiac murmur. Investigations revealed infective aortitis of a pre-existing aortic aneurysm graft repair. Peripheral blood cultures were positive for Yersinia pseudotuberculosis and the patient was successfully treated with an extended course of antibiotics. Abdominal imaging also revealed progressive bilateral polycystic kidney disease with associated diverticular disease, which was postulated as the source of the Y. pseudotuberculosis. An autosomal dominant polycystic kidney disease may present late in life and extra-renal manifestations of this disease are an important cause of morbidity. PMID:26634143

  10. 应用SYBR GreenⅠ实时荧光定量聚合酶链反应检测常染色体隐性遗传早发性帕金森综合征的parkin基因外显子重排突变%Analysis of exon rearrangements in the parkin gene in patients with autosomal recessive early-onset parkinsonism using SYBR Green Ⅰ Real-time PCR

    Institute of Scientific and Technical Information of China (English)

    唐北沙; 严新翔; 聂利珞; 郭纪锋; 张海南; 张学伟; 王磊; 沈璐; 江泓; 夏昆

    2009-01-01

    目的 建立应用SYBR GreenⅠ实时荧光定量聚合酶链反应(Real-time PCR,RT-PCR)检测parkin基因外显子重排突变的技术平台,应用该技术对常染色体隐性遗传早发型帕金森综合征(autosomal recessive early-onset parkinsonism,AREP) 家系进行parkin基因外显子重排突变分析.方法 应用SYBR GreenⅠRT-PCR技术对32个中国AREP家系进行parkin基因外显子重排突变分析.结果 14个家系先证者存在parkin基因外显子重排突变,其中3个为纯合缺失突变、3个为复杂杂合缺失突变和8个杂合缺失突变,未发现外显子重复突变,突变主要累及第2~4号外显子.结论 建立了应用SYBR GreenⅠRT-PCR技术检测parkin基因外显子重排突变的基因检测平台;中国AREP 家系的parkin基因外显子重排突变频率为43.8%,与国外报道相似.%Objective To develop a method of detection exon rearrangements in the parkin gene (PARK2) using SYBR Green Ⅰ real-time PCR and to analyze PARK2 exon rearrangement mutations in families with autosomal recessive early-onset parkinsonism (AREP) using this method. Methods Exon rearrangement in PARK2 was screened by SYBR Green Ⅰ real-time PCR in 32 families with AREP. Results Exon rearrangement mutations were found in 14 families, including 3 compound heterozygous deletions;3 homozygous deletions;and 8 heterozygous deletions. No duplication mutation was found. Hotspot for exon rearrangements clustered in exons 2 through 4. Conclusions We have developed a gene test method using SYBR Green Ⅰ Real-time PCR to detect exon rearrangements in the gene PARK2. The frequency of PARK2 mutation is 43.8% in Chinese families with AREP. This frequency is similar to reported findings in other countries.

  11. Caroli′s syndrome in a post renal transplant patient: Case report and review of the literature

    OpenAIRE

    Bawany, Muhammad Z; Osama Alaradi; Ali Nawras

    2012-01-01

    Caroli's syndrome is characterized by bile duct ectasia in association with hepatic fibrosis. It is usually transmitted in an autosomal recessive fashion and has been well documented to be associated with autosomal recessive polycystic kidney disease and occasionally with autosomal dominant polycystic kidney disease. However, there has been only few case reports published with Caroli's syndrome diagnosed postrenal transplantation.

  12. Forecasting US Recessions

    DEFF Research Database (Denmark)

    Christiansen, Charlotte; Eriksen, Jonas Nygaard; Møller, Stig Vinther

    2014-01-01

    We study the role of sentiment variables as predictors for US recessions. We combine sentiment variables with either classical recession predictors or common factors based on a large panel of macroeconomic and financial variables. Sentiment variables hold vast predictive power for US recessions in...

  13. Regime-dependent recession forecasts and the 2001 recession

    OpenAIRE

    Dueker, Michael J.

    2002-01-01

    Business recessions are notoriously hard to predict accurately, hence the quip that economists have predicted eight of the last five recessions. This article derives a six-month-ahead recession signal that reduces the number of false signals outside of recession, without impairing the ability to signal the recessions that occur. In terms of predicting the 1990-91 and 2001 recessions out of sample, the new recession signal, like other signals, largely misses the 1990-91 recession with its six-...

  14. Polycystic Kidney Disease

    Science.gov (United States)

    ... cysts abnormal heart valves diverticula brain aneurysms A health care provider diagnoses autosomal dominant PKD using imaging tests and genetic testing. A radiologist—a doctor who specializes in medical imaging—will ...

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

    Institute of Scientific and Technical Information of China (English)

    麻宏伟; 武盈玉; 王阳; 高薇; 薛燕宁

    2001-01-01

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

  16. POLYCYSTIC OVARY SYNDROME

    OpenAIRE

    Akula Annapurna

    2013-01-01

    Polycystic ovary syndrome is a condition in which a woman has an imbalance of female sex hormones. This may lead to menstrual cycle changes, cysts in the ovaries, trouble getting pregnant, and other health changes. In PCOS, mature eggs are not released from the ovaries. Instead, they can form very small cysts in the ovary. These changes can contribute to infertility. Common symptoms of PCOS include Menstrual disorders, Infertility, High levels of testosterone and Metabolic syndrome. Obesity, ...

  17. Exon rearrangement analysis of parkin gene in patients with autosomal recessive early-onset parkinsonism using fluorescent semi-quantitative PCR%应用荧光半定量聚合酶链反应方法检测常染色体隐性遗传早发性帕金森综合征parkin基因外显子重排突变分析

    Institute of Scientific and Technical Information of China (English)

    郭纪锋; 蔡芳; 潘乾; 沈璐; 江泓; 唐北沙; 夏昆; 严新翔; 张玉虎; 陈涛; 李静; 张学伟; 曹立

    2006-01-01

    目的探讨常染色体隐性遗传早发性帕金森综合征(autosomal recessive early-onset parkinsonism,AREP)parkin基因外显子重排突变情况.方法应用荧光半定量聚合酶链反应(PCR)方法对18个AREP家系进行parkin基因外显子重排突变分析.结果9个AREP家系含有parkin基因外显子重排突变,其中2个家系为外显子4纯合缺失,2个家系为外显子4杂合缺失,2个家系为外显子2杂合缺失,1家系为外显子3杂合缺失,1家系为外显子1杂合缺失,此外,1家系为外显子3和外显子4的复合杂合缺失.未见parkin基因外显子重复突变.结论我国AREP患者存在parkin基因外显子重排突变;parkin基因外显子重排突变可能是我国AREP患者的主要致病因素.

  18. Transcatheter Arterial Embolization Using Ethanol in a Dialysis Patient for Contracting Enlarged Polycystic Kidneys

    Energy Technology Data Exchange (ETDEWEB)

    Rim, Hark; Jung, Gyoo Sik; Jung, Yeon Soon [Kosin University College of Medicine, Gospel Hospital, Busan (Korea, Republic of)

    2010-10-15

    The mass effect of nephromegaly in patients with autosomal dominant polycystic kidney disease may cause pain and symptoms by compressing the alimentary tract, lungs, and heart. Conventional therapies exist to contract enlarged polycystic kidneys including surgical and interventional procedures. A surgical nephrectomy is often difficult to perform in dialysis patients due to the associated risks related to surgery. In contrast, renal transcatheter arterial embolization (TAE) with metallic coils, which is a less invasive interventional procedure, can also be utilized to contract enlarged kidneys in dialysis patients as an effective treatment. However, metallic coils present the possibility of recanalization and cost issues. Thus, we used ethanol instead of coils in renal TAE to resolve these issues. We report a dialysis patient with enlarged polycystic kidneys and poor oral intake due to abdominal distention that was successfully treated by TAE with absolute ethanol

  19. Transcatheter Arterial Embolization Using Ethanol in a Dialysis Patient for Contracting Enlarged Polycystic Kidneys

    International Nuclear Information System (INIS)

    The mass effect of nephromegaly in patients with autosomal dominant polycystic kidney disease may cause pain and symptoms by compressing the alimentary tract, lungs, and heart. Conventional therapies exist to contract enlarged polycystic kidneys including surgical and interventional procedures. A surgical nephrectomy is often difficult to perform in dialysis patients due to the associated risks related to surgery. In contrast, renal transcatheter arterial embolization (TAE) with metallic coils, which is a less invasive interventional procedure, can also be utilized to contract enlarged kidneys in dialysis patients as an effective treatment. However, metallic coils present the possibility of recanalization and cost issues. Thus, we used ethanol instead of coils in renal TAE to resolve these issues. We report a dialysis patient with enlarged polycystic kidneys and poor oral intake due to abdominal distention that was successfully treated by TAE with absolute ethanol

  20. Association between Nephrolithiasis, Hypertension and Obesity in Polycystic Kidney Disease

    Science.gov (United States)

    Bajrami, Valbona; Idrizi, Alma; Roshi, Enver; Barbullushi, Myftar

    2016-01-01

    AIM: We aim to define the correlations between nephrolithiasis, hypertension, age and obesity in patients with autosomal dominant polycystic kidney disease (ADPKD) in Albania. MATERIAL AND METHODS: We included 100 patients with autosomal dominant polycystic kidney from 2011 to 2014. The patients underwent X-ray and renal ultrasonography. We performed the metabolic evaluation of blood and urine. RESULTS: The patients with renal stones had a higher level of mean systolic and diastolic blood pressure compared with patients without stones (155 ± 12 mmHg vs. 145 ± 8 mmHg, and 105 ± 0.9 mmHg vs. 92 ± 1.28 mmHg, respectively). Patients with renal stones were older (47 ± 15 vs. 38 ± 5 years), had a higher prevalence of obesity [body mass index (BMI): 28 ± 2.4 vs. 25.7 ± 0.6], had higher levels of total cholesterol level (220 ± 5 mg/dl vs. 203 ± 4 mg/dl) as well as triglyceride levels (160 ± 9 mg/dl vs. 126 ± 4 mg/dl), compared with no renal stone individuals. CONCLUSION: ADPKD patients with renal stones in our study had a higher mean level of systolic and diastolic blood pressure, BMI and cholesterol and triglycerides levels compared with individuals without renal stones.

  1. Association between Nephrolithiasis, Hypertension and Obesity in Polycystic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Valbona Bajrami

    2015-12-01

    Full Text Available AIM: We aim to define the correlations between nephrolithiasis, hypertension, age and obesity in patients with autosomal dominant polycystic kidney disease (ADPKD in Albania. MATERIAL AND METHODS: We included 100 patients with autosomal dominant polycystic kidney from 2011 to 2014. The patients underwent X-ray and renal ultrasonography. We performed the metabolic evaluation of blood and urine. RESULTS: The patients with renal stones had a higher level of mean systolic and diastolic blood pressure compared with patients without stones (155 ± 12 mmHg vs. 145 ± 8 mmHg, and 105 ± 0.9 mmHg vs. 92 ± 1.28 mmHg, respectively. Patients with renal stones were older (47 ± 15 vs. 38 ± 5 years, had a higher prevalence of obesity [body mass index (BMI: 28 ± 2.4 vs. 25.7 ± 0.6], had higher levels of total cholesterol level (220 ± 5 mg/dl vs. 203 ± 4 mg/dl as well as triglyceride levels (160 ± 9 mg/dl vs. 126 ± 4 mg/dl, compared with no renal stone individuals. CONCLUSION: ADPKD patients with renal stones in our study had a higher mean level of systolic and diastolic blood pressure, BMI and cholesterol and triglycerides levels compared with individuals without renal stones.

  2. UNUSUAL CASE OF POLYCYSTIC LIVER DISEASE

    Directory of Open Access Journals (Sweden)

    Andreea Brumaru

    2005-01-01

    Full Text Available Polycystic liver disease (PCLD is a rare disease defined as the presence of four or more thin-walled cyst within the hepatic parenchyma.The most common form of autosomal dominant PCLD coexist with renal cystic disease. In contrast to the concomitant renal and liver cystic disease, the isolated form of PCLD is a comparatively rare form, that displays no renal involvement.Only 7% of patients with PCDL do not have associated renal cyst. Most cases are asymptomatic. Patients generally have preserved hepatic functions.The liver function tests are normal. Polycystic liver is rarely associated with portal hypertension , obstructive jaundice or infection of hepatic cysts. Autopsy series show that 20 % of patients with PCLD have associated intracranial aneurism. There are no effective medical therapies for PCLD.Surgical options for those with refractory symptoms or complications include percutaneous puncture and sclerosys of cysts, cysts fenestration by open or laparoscopic technique, hepatic resection, and isolated hepatic or combined liver kidney transplantation. We present the case of a 68 years male subject , diagnosed with alcoholic liver cirrhosis based on the chronic alcohol consumption,negative serological markers for the B and C hepatitis viruses, hepatoprive and biliar retention tests, portal hypertension. The abdominal echography revealed a diffuse enlargement of the liver , witch contains numerous cysts scattered throughout the liver. The cysts vary in size from less than 1 cm to more than 5 cm. There is no evidence of renal or pancreatic cysts. The treatment is addressed to the portal hypertension due to alcoholic liver disease. The PCLD is not complicated and therefore requires no surgical treatment.

  3. Lack of Benefit of Early Intervention with Dietary Flax and Fish Oil and Soy Protein in Orthologous Rodent Models of Human Hereditary Polycystic Kidney Disease

    Science.gov (United States)

    Monirujjaman, Md; Gabbs, Melissa

    2016-01-01

    Rationale for dietary advice in polycystic kidney disease (PKD) is based in part on animal studies that have examined non-orthologous models with progressive development of cystic disease. Since no model completely mimics human PKD, the purpose of the current studies was to examine the effects of dietary soy protein (compared to casein) or oils enriched in omega-3 fatty acids (fish or flax oil compared to soy oil) on early disease progression in two orthologous models of PKD. The models studied were Pkd2WS25/- mice as a model of autosomal dominant PKD, and PCK rats as a model of autosomal recessive PKD. After 13 weeks of feeding, dietary fish (but not flax) oil resulted in larger kidneys and greater kidney water content in female Pkd2WS25/- compared to control mice. After 12 weeks of feeding male PCK compared to control rats, both fish and flax compared to soy oil resulted in enlarged kidneys and livers, greater kidney water content and higher kidney cyst area in diseased rats. Dietary soy protein compared to casein had no effects in Pkd2WS25/- compared to control mice. In PCK rats, kidney and liver histology were not improved, but lower proteinuria and higher urine pH suggest that soy protein could be beneficial in the long term. Therefore, in contrast to studies in non-orthologous models during the progressive development phase, these studies in orthologous PKD models do not support dietary advice to increase soy protein or oils enriched in omega-3 oils in early PKD. PMID:27213553

  4. [Polycystic ovary syndrome].

    Science.gov (United States)

    Vrbíková, Jana

    2015-10-01

    For diagnosing of polycystic ovary syndrome (PCOS) it is currently recommended to follow the ESHRE criteria. For diagnosis according to them two of the following three symptoms are sufficient: 1. morphology of polycystic ovaria, 2. clinical manifestations of hyperandrogenism or laboratory proof of hyperandrogenemia, and 3. oligo-anovulation. PCOS is a complex disorder in whose pathogenesis genetic and environmental effects interact. It is not a gynecological disorder alone, the syndrome is accompanied by insulin resistance which leads to increased incidence of type 2 diabetes mellitus and impaired glucose tolerance (4 times and twice, independently of BMI). Also gestational DM occurs more frequently. Dyslipidemia, arterial hypertension, elevated CRP and homocysteine levels, endothelial dysfunction and greater intima-media thickness are also more frequent. It is not quite clear, however, whether women with PCOS suffer cardiovascular events more frequently as well. More often than is accidental PCOS is associated with depression, anxiety and eating disorders, further with nonalcoholic steatohepatitis and with the sleep apnoea syndrome - especially in obese women. Therapeutic measures include non-pharmacological methods - lifestyle adjustments focused on weight reduction in obese individuals, cosmetic measures for dermatologic manifestation of hyperandrogenism, in particular laser and pharmacotherapy (combined hormonal contraceptives and antiandrogens). Menstrual irregularities can be treated with contraceptives or cyclical administration of gestagens, also metformin can be used. PMID:26486483

  5. Recession in the Regions

    Science.gov (United States)

    Plant, Helen

    2009-01-01

    National policy stresses the key role of adult learning and skills in securing economic recovery. This close linking of adult learning policy to the recession agenda raises important questions. How has the recession impacted on the implementation of adult learning policy? What has it meant for service delivery? And what have been the consequences…

  6. Polycystic ovary syndrome and hirsutism

    OpenAIRE

    Evliyaoğlu, Olcay

    2011-01-01

    Polycystic ovary syndrome is a multi factorial heterogenous disorder characterized by chronic anovulation and hyperandrogenism Diagnosis is based on clinical or laboratory evidence of nbsp; hyperandrogenism nbsp; For diagnosis at least two of the three Rotterdam criteria oligo anovulation clinical or biochemical signs of hyperandrogenism polycystic ovaries nbsp; should be ensured Clinical symptoms usually begin around menarche nbsp; Oligomenorrhea amenorrhea hirsutism acne alopecia can be ass...

  7. 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....

  8. Polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    Nina Madnani

    2013-01-01

    Full Text Available Polycystic ovarian syndrome (PCOS is a "multispeciality" disorder suspected in patients with irregular menses and clinical signs of hyperandrogenism such as acne, seborrhoea, hirsutism, irregular menses, infertility, and alopecia. Recently, PCOS has been associated with the metabolic syndrome. Patients may develop obesity, insulin resistance, acanthosis nigricans, Type 2 diabetes, dyslipidemias, hypertension, non-alcoholic liver disease, and obstructive sleep apnoea. Good clinical examination with hematological and radiological investigations is required for clinical evaluation. Management is a combined effort involving a dermatologist, endocrinologist, gynecologist, and nutritionist. Morbidity in addition includes a low "self image" and poor quality of life. Long term medications and lifestyle changes are essential for a successful outcome. This article focuses on understanding the normal and abnormal endocrine functions involved in the pathogenesis of PCOS. Proper diagnosis and management of the patient is discussed.

  9. Polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Aziz, Mubeena; Sidelmann, Johannes J; Faber, Jens;

    2015-01-01

    INTRODUCTION: Polycystic ovary syndrome (PCOS) is associated with obesity and insulin resistance. The objective of this cross-sectional study was to investigate the impact of insulin resistance and body mass index (BMI) on inflammatory and hemostatic variables associated with long-term risk of...... cardiovascular disease in women with PCOS. MATERIAL AND METHODS: 149 premenopausal women with PCOS were recruited consecutively from April 2010 to February 2012 at three Danish University Hospitals. The study was conducted at the Department of Gynecology and Obstetrics, Herlev University Hospital, Denmark. PCOS...... measures were the biomarkers C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), and von Willebrand factor antigen. RESULTS: Normal weight insulin-resistant PCOS women were characterized by abdominal obesity and elevated levels of plasma PAI-1. Overweight/obese insulin-resistant PCOS women...

  10. Optimising the management of polycystic kidney disease.

    Science.gov (United States)

    Keenan, Declan; Maxwell, Alexander P

    2016-02-01

    Polycystic kidney disease (PKD) is the most common inherited renal disorder that results in chronic kidney disease. PKD has an autosomal dominant pattern of inheritance. The prevalence is between 1:500 and 1:1,000. Up to 10% of adults with end-stage renal disease (ESRD) have a genetic disorder such as PKD. A family history of PKD may be absent in up to 25% of affected individuals. The most common clinical features are visible haematuria, loin pain, UTI and hypertension. The typical clinical course is a progressive increase in the number and size of renal cysts associated with gradual loss of kidney function (falling eGFR). Risk factors for progression include: younger age at diagnosis; large kidney volume; rapid cyst growth; hypertension; male gender; and visible haematuria. Approximately 50% of individuals with PKD will require renal replacement therapy by the sixth decade of life. PKD is a multisystem disorder associated with multiple bilateral renal cysts, slowly increasing kidney size and progressive chronic kidney disease. Diagnosis of PKD is confirmed by ultrasound showing the presence of multiple kidney cysts. More than 80% will also have multiple liver cysts, which can lead to local pressure effects. Cerebral haemorrhage, secondary to rupture of a berry aneurysm, occurs in up to 8% of individuals. Mitral valve prolapse occurs in up to 25% of patients. PMID:27032221

  11. Who Suffers During Recessions?

    OpenAIRE

    Hilary Hoynes; Miller, Douglas L.; Jessamyn Schaller

    2012-01-01

    In this paper, we examine how business cycles affect labor market outcomes in the United States. We conduct a detailed analysis of how cycles affect outcomes differentially across persons of differing age, education, race, and gender, and we compare the cyclical sensitivity during the Great Recession to that in the early 1980s recession. We present raw tabulations and estimate a state panel data model that leverages variation across U.S. states in the timing and severity of business cycles. W...

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

    OpenAIRE

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

    1988-01-01

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

  13. POLYCYSTIC OVARY SYNDROME

    Directory of Open Access Journals (Sweden)

    Akula Annapurna

    2013-09-01

    Full Text Available Polycystic ovary syndrome is a condition in which a woman has an imbalance of female sex hormones. This may lead to menstrual cycle changes, cysts in the ovaries, trouble getting pregnant, and other health changes. In PCOS, mature eggs are not released from the ovaries. Instead, they can form very small cysts in the ovary. These changes can contribute to infertility. Common symptoms of PCOS include Menstrual disorders, Infertility, High levels of testosterone and Metabolic syndrome. Obesity, sedentary life style with inadequate physical activity, stress, junk food consumption are thought to be contributing factors in addition to genetic origin. In recent years many of the girls and women are suffering from PCOS because of wrong eating habits, stressful living conditions and lack of physical activity. Weight loss has been the major recommendation by physicians for women with PCOS. Lifestyle modifications including stress reduction, moderate exercise, and group support, along with a decrease in total calorie intake and avoiding junk food consumption have had positive results. A decrease of only 5% of total body weight is associated with decreased insulin levels, increased fertility, reduced hirsutism and acne, and lower testosterone levels. Whole grains, fruits and vegetables with foods containing protein and natural fat along with vitamins and minerals are beneficial.

  14. Bardet–Biedl syndrome proteins 1 and 3 regulate the ciliary trafficking of polycystic kidney disease 1 protein

    OpenAIRE

    Su, Xuefeng; Driscoll, Kaitlin; Yao, Gang; Raed, Anas; Wu, Maoqing; Beales, Philip L.; Zhou, Jing

    2014-01-01

    Bardet–Biedl syndrome (BBS) and autosomal dominant polycystic kidney disease (ADPKD) are two genetically distinct ciliopathies but share common phenotypes such as renal cysts. Seven BBS proteins form a complex called the BBSome which is localized at the basal body or ciliary axoneme and regulates the ciliary entry or flagellar exit of several signaling molecules. Here, we demonstrate that, unlike the seven-span somatostatin receptor 3 or the leptin receptor that interacts with all subunits of...

  15. Elevated Dehydroepiandrosterone Sulfate Levels as the Reproductive Phenotype in the Brothers of Women with Polycystic Ovary Syndrome

    OpenAIRE

    Legro, Richard S.; Kunselman, Allen R.; DEMERS, LAWRENCE; Wang, Steve C.; Bentley-Lewis, Rhonda; Dunaif, Andrea

    2002-01-01

    There is an inherited susceptibility to polycystic ovary syndrome (PCOS). Some investigators have suggested that premature male-pattern balding is a male phenotype in PCOS families, but this remains controversial. We recently reported evidence for an autosomal monogenic abnormality in ovarian and adrenal steroidogenesis in the sisters of women with PCOS. We performed this study to determine whether we could identify a clinical or biochemical phenotype in the brothers of women with PCOS. One h...

  16. PREDICTION OF RECESSION

    OpenAIRE

    Lee, Young Sub; Zhu, Qian

    2010-01-01

    The purpose of our research is to examine the predictive power of inverted yield curve for the recession in the near future. The data used in this research are between Jan 1, 1959 to Nov, 2008. There are 8 recessions during this period, including current one. We conducted two sets of tests. The first set consists of spread between 10-year Treasury bond and 3-month Treasury bill and spread between 10-year Treasury bond and 3-month LIBOR; and we find the predictive power of spread between 10-ye...

  17. Gingival Recessions and Biomechanics

    DEFF Research Database (Denmark)

    Laursen, Morten Godtfredsen

    Gingival recessions and biomechanics “Tissue is the issue, but bone sets the tone.“ A tooth outside the cortical plate can result in loss of bone and development of a gingival recession. The presentation aims to show biomechanical considerations in relation to movement of teeth with gingival...... by moving the root back in the alveolus. The tooth movement is accompanied by bone gain and thus increase the success rate for soft tissue augmentation. The choice of biomechanical system influences the treatment outcome. If a standard straight wire appliance is used, a biomechanical dilemma can arise...

  18. Overweight in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Ravn, P; Haugen, A G; Glintborg, D

    2013-01-01

    Aim: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in premenopausal women affecting 5-10%. Nearly 50% are overweight or obese, which result in a more severe phenotype of PCOS. Weight loss is therefore considered the first line treatment in overweight women with PCOS...

  19. LAMB3 mutations causing autosomal-dominant amelogenesis imperfecta.

    Science.gov (United States)

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

    2013-10-01

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

  20. Recession or Not?

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Economists are at odds over whether the United States has entered an economic recession,although several factors appear to indicate it has During the latter half of the year 2007, bad news about the U.S.economy would not stop coming.The sub- prime mortgage crisis appeared to

  1. Polycystic liver disease: an overview of pathogenesis, clinical manifestations and management.

    Science.gov (United States)

    Cnossen, Wybrich R; Drenth, Joost P H

    2014-01-01

    Polycystic liver disease (PLD) is the result of embryonic ductal plate malformation of the intrahepatic biliary tree. The phenotype consists of numerous cysts spread throughout the liver parenchyma. Cystic bile duct malformations originating from the peripheral biliary tree are called Von Meyenburg complexes (VMC). In these patients embryonic remnants develop into small hepatic cysts and usually remain silent during life. Symptomatic PLD occurs mainly in the context of isolated polycystic liver disease (PCLD) and autosomal dominant polycystic kidney disease (ADPKD). In advanced stages, PCLD and ADPKD patients have massively enlarged livers which cause a spectrum of clinical features and complications. Major complaints include abdominal pain, abdominal distension and atypical symptoms because of voluminous cysts resulting in compression of adjacent tissue or failure of the affected organ. Renal failure due to polycystic kidneys and non-renal extra-hepatic features are common in ADPKD in contrast to VMC and PCLD. In general, liver function remains prolonged preserved in PLD. Ultrasonography is the first instrument to assess liver phenotype. Indeed, PCLD and ADPKD diagnostic criteria rely on detection of hepatorenal cystogenesis, and secondly a positive family history compatible with an autosomal dominant inheritance pattern. Ambiguous imaging or screening may be assisted by genetic counseling and molecular diagnostics. Screening mutations of the genes causing PCLD (PRKCSH and SEC63) or ADPKD (PKD1 and PKD2) confirm the clinical diagnosis. Genetic studies showed that accumulation of somatic hits in cyst epithelium determine the rate-limiting step for cyst formation. Management of adult PLD is based on liver phenotype, severity of clinical features and quality of life. Conservative treatment is recommended for the majority of PLD patients. The primary aim is to halt cyst growth to allow abdominal decompression and ameliorate symptoms. Invasive procedures are required

  2. Two Cases of Polycystic Kidneys in Two Siblings

    Directory of Open Access Journals (Sweden)

    S.D. Kamyab

    1976-07-01

    Full Text Available Polycystic disease of th e kidneys is a genetalized lesion o f charact erist ic clinico-pathological enti ty. It has two c1in cial fo rms: adult and infantile . The adult type is transmitted as a dominan t disease where the latter is a recessive trait. The infantile form had two pathological patterns, Form "A" in which the kidney is large and spo ngy , of normal shape and the cyst s are numerous. Microscopically the co nnective tissue is not increased. The cysts are of eq ual size and shape. The ncph rons are not reduced . In th e form "B" t he kidney may not have a normal shape and is not as large as the form "A" . Microscopica ll y the connect ive t issue is increased intensively. The cysts are of spherical shape and different sizes. The nephrons are reduced in number.

  3. Chromosomal deletion unmasking a recessive disease: 22q13 deletion syndrome and metachromatic leukodystrophy

    DEFF Research Database (Denmark)

    Bisgaard, A-M; Kirchhoff, M; Nielsen, J E; Kibaek, M; Lund, A; Schwartz, M; Christensen, E

    2008-01-01

    A deletion on one chromosome and a mutant allele on the other may cause an autosomal recessive disease. We report on two patients with mental retardation, dysmorphic features and low catalytic activity of arylsulfatase A. One patient had a pathogenic mutation in the arylsulfatase A gene (ARSA) and...

  4. [Cardiovascular risk in polycystic kidney disease].

    Science.gov (United States)

    Di Lorenzo, Adelaide; Stallone, Giovanni; Infante, Barbara; Grandaliano, Giuseppe; Schena, Francesco Paolo

    2015-09-01

    Hypertension is common and occurs in the majority of autosomal dominant polycystic kidney disease (ADPKD) patients prior to loss of kidney function. Hypertension relates to progressive kidney enlargement, and is a significant independent risk factor for progression to end-stage renal disease. The pathogenesis of hypertension in ADPKD is complex and depends on many factors that influence each other. High expression of PKD1 and PKD2 genes is present in the cilia of tubular epithelial cells, in endothelial cells and in vascular smooth muscle cells. Decreased or absent polycystin-1 or -2 expression is associated with abnormal vascular structure and function. PKD1/PKD2 deficiency results in reduced nitric oxide levels, altered endothelial response to shear stress with attenuation in vascular relaxation. Activation of the renin-angiotensin-aldosterone system occurs in ADPKD due to decreased nitric oxide production as well as bilateral cyst expansion and intra-renal ischemia. With increasing cyst size, further activation of the renin-angiotensin-aldosterone system occurs, blood pressure increases and a vicious cycle ensues with enhanced cyst growth and hypertension ultimately leading to end-stage renal disease. Inhibition of the angiotensin-aldosterone system is possible with angiotensin-converting enzyme inhibitors and seems to be the first-line treatment for hypertension in these subjects. As suggested by the HALT-PKD study, an aggressive blood pressure control is safe and recommended and is associated with preservation of kidney function and a reduction in total kidney volume over time. A collaborative multidisciplinary approach between nephrologists and cardiologists is necessary for the monitoring of kidney and heart complications. PMID:26418387

  5. Deep sequencing reveals 50 novel genes for recessive cognitive disorders.

    Science.gov (United States)

    Najmabadi, Hossein; Hu, Hao; Garshasbi, Masoud; Zemojtel, Tomasz; Abedini, Seyedeh Sedigheh; Chen, Wei; Hosseini, Masoumeh; Behjati, Farkhondeh; Haas, Stefan; Jamali, Payman; Zecha, Agnes; Mohseni, Marzieh; Püttmann, Lucia; Vahid, Leyla Nouri; Jensen, Corinna; Moheb, Lia Abbasi; Bienek, Melanie; Larti, Farzaneh; Mueller, Ines; Weissmann, Robert; Darvish, Hossein; Wrogemann, Klaus; Hadavi, Valeh; Lipkowitz, Bettina; Esmaeeli-Nieh, Sahar; Wieczorek, Dagmar; Kariminejad, Roxana; Firouzabadi, Saghar Ghasemi; Cohen, Monika; Fattahi, Zohreh; Rost, Imma; Mojahedi, Faezeh; Hertzberg, Christoph; Dehghan, Atefeh; Rajab, Anna; Banavandi, Mohammad Javad Soltani; Hoffer, Julia; Falah, Masoumeh; Musante, Luciana; Kalscheuer, Vera; Ullmann, Reinhard; Kuss, Andreas Walter; Tzschach, Andreas; Kahrizi, Kimia; Ropers, H Hilger

    2011-10-01

    Common diseases are often complex because they are genetically heterogeneous, with many different genetic defects giving rise to clinically indistinguishable phenotypes. This has been amply documented for early-onset cognitive impairment, or intellectual disability, one of the most complex disorders known and a very important health care problem worldwide. More than 90 different gene defects have been identified for X-chromosome-linked intellectual disability alone, but research into the more frequent autosomal forms of intellectual disability is still in its infancy. To expedite the molecular elucidation of autosomal-recessive intellectual disability, we have now performed homozygosity mapping, exon enrichment and next-generation sequencing in 136 consanguineous families with autosomal-recessive intellectual disability from Iran and elsewhere. This study, the largest published so far, has revealed additional mutations in 23 genes previously implicated in intellectual disability or related neurological disorders, as well as single, probably disease-causing variants in 50 novel candidate genes. Proteins encoded by several of these genes interact directly with products of known intellectual disability genes, and many are involved in fundamental cellular processes such as transcription and translation, cell-cycle control, energy metabolism and fatty-acid synthesis, which seem to be pivotal for normal brain development and function. PMID:21937992

  6. Bank Profitability during Recessions

    OpenAIRE

    Wilko Bolt; Leo de Haan; Marco Hoeberichts; Maarten van Oordt; Job Swank

    2010-01-01

    This paper estimates the relation between bank profitability and economic downturns using a theoretical model that takes into account the bank's lending history as well as amortization and losses on outstanding loans. We focus on total bank profits and its components: net interest income, other income, and net provisioning plus other costs. Using both aggregate and individual bank panel datasets, our results confirm that pro-cyclicality of bank profits is stronger for deep recessions than dur...

  7. Fiscal Multipliers in Recessions

    OpenAIRE

    Canzoneri, Matthew; Collard, Fabrice; Dellas, Harris; Diba, Behzad

    2015-01-01

    The Great Recession, and the fiscal response to it, has revived interest in the size of fiscal multipliers. Standard business cycle models have difficulties generating multipliers greater than one. And they also cannot produce any significant state-dependence in the size of the multipliers over the business cycle. In this paper we employ a variant of the Curdia-Woodford model of costly financial intermediation and show that fiscal multipliers can be strongly state dependent in a countercyclic...

  8. [Diagnostics of polycystic ovary syndrome].

    Science.gov (United States)

    Lazúrová, Ivica; Figurová, Jana; Lazúrová, Zora

    2015-12-01

    Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy among women of reproductive age and the most frequent cause of menstruation cycle disorders. It is marked by a hyperandrogenic state (clinical and/or biochemical) and ovulatory dysfunction (anovulation and/or ultrasonographic finding of polycystic ovaries), which are also criteria for its diagnosis according to Androgen Excess and PCOS Society. The syndrome has multiple phenotypic expressions, among them besides the above characteristics also a metabolic syndrome, primarily obesity and insulin resistance. Diagnosing of PCOS may be rather exacting in clinical practice and it remains to be a diagnosis per exclusionem, following elimination of other causes of hyperandrogenic state and chronic oligo-anovulation. It requires a close cooperation between a gynecologist and endocrinologist and with regard to frequent metabolic complications also with an internist, diabetologist and possibly cardiologist. PMID:27124971

  9. A novel mutation causing nephronophthisis in the Lewis polycystic kidney rat localises to a conserved RCC1 domain in Nek8

    Directory of Open Access Journals (Sweden)

    McCooke John K

    2012-08-01

    Full Text Available Abstract Background Nephronophthisis (NPHP as a cause of cystic kidney disease is the most common genetic cause of progressive renal failure in children and young adults. NPHP is characterized by abnormal and/or loss of function of proteins associated with primary cilia. Previously, we characterized an autosomal recessive phenotype of cystic kidney disease in the Lewis Polycystic Kidney (LPK rat. Results In this study, quantitative trait locus analysis was used to define a ~1.6Mbp region on rat chromosome 10q25 harbouring the lpk mutation. Targeted genome capture and next-generation sequencing of this region identified a non-synonymous mutation R650C in the NIMA (never in mitosis gene a- related kinase 8 ( Nek8 gene. This is a novel Nek8 mutation that occurs within the regulator of chromosome condensation 1 (RCC1-like region of the protein. Specifically, the R650C substitution is located within a G[QRC]LG repeat motif of the predicted seven bladed beta-propeller structure of the RCC1 domain. The rat Nek8 gene is located in a region syntenic to portions of human chromosome 17 and mouse 11. Scanning electron microscopy confirmed abnormally long cilia on LPK kidney epithelial cells, and fluorescence immunohistochemistry for Nek8 protein revealed altered cilia localisation. Conclusions When assessed relative to other Nek8 NPHP mutations, our results indicate the whole propeller structure of the RCC1 domain is important, as the different mutations cause comparable phenotypes. This study establishes the LPK rat as a novel model system for NPHP and further consolidates the link between cystic kidney disease and cilia proteins.

  10. Metformin and Polycystic Ovary Syndrome

    OpenAIRE

    Omran, Maha Yousef Soliman

    2007-01-01

    The polycystic ovary syndrome (PCOS), one of the most common causes of infertility due to anovulation, affects 4–7% of women). Etiology of PCOS remains largely unknown, familial aggregation of cases suggests genetic susceptibility to the disorder. Though genes involved remain unknown, recent evidence points to a gene of the insulin receptor. Genes implicated in ovarian follicular development may also play a role. A fundamental aspect of the syndrome seems to be a defect in insulin metabolism....

  11. Polycystic Ovary Syndrome in Adolescence

    OpenAIRE

    Buggs, Colleen; Rosenfield, Robert L.

    2005-01-01

    Polycystic ovary syndrome (PCOS) is a syndrome of variable combinations of menstrual irregularity, hirsutism or acne, and obesity. It can be diagnosed in adolescence and has early childhood antecedents. PCOS is the single most common endocrine cause of anovulatory infertility and a major risk factor for the metabolic syndrome and, in turn, development of type 2 diabetes mellitus (T2DM) in women. Thus, it appears that PCOS increases a woman’s risk of developing cardiovascular disease. Therefor...

  12. 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

  13. An autosomal locus causing autoimmune disease: Autoimmune polyglandular disease type I assigned to chromosome 21

    OpenAIRE

    Aaltonen, Johanna; Björses, Petra; Sandkuijl, Lodewijk; Perheentupa, Jaakko; Peltonen, Leena Johanna

    1994-01-01

    textabstractAutoimmune polyglandular disease type I (APECED) is an autosomal recessive autoimmune disease characterized by a variable combination of the failure of the endocrine glands. The pathogenesis of this unique autoimmune disease is unknown; unlike many other autoimmune diseases, APECED does not show association to specific HLA haplotypes. Unravelling the APECED locus will identify a novel gene outside the HLA loci influencing the outcome of autoimmune diseases. We have assigned the di...

  14. 常染色体隐性遗传早发性帕金森病1个家系临床特征及parkin基因突变分析%The clinical characteristics and mutation analysis of parkin gene in a family with autosomal recessive early-onset parkinsonism

    Institute of Scientific and Technical Information of China (English)

    柳四新; 郭纪锋; 唐北沙; 李静; 严新翔

    2008-01-01

    目的 探讨1个常染色体隐性遗传早发性帕金森病(autosornal recessive early-onset parkinson-ism,AREP)家系的临床特征及parkin基因突变情况.方法 对1个AREP家系2例患者的临床资料进行回顾性分析,同时应用DNA直接测序、限制性内切酶酶切、荧光半定量PCR等技术方法进行parkin基因的突变分析.结果 该家系共2例患者,发病年龄轻,分别为22岁和23岁;病情进展相对缓慢,症状有波动,呈晨轻暮重,腱反射活跃;对小剂量多巴制剂反应良好.基因突变发现该家系存在parkin基因的复合杂合突变(第7号外显子杂合的G859T和第4外显子杂合缺失突变),其中G859T为新报道的点突变.结论 我国的AREP家系有帕金森病的一般临床表现,又有其独特的临床特征,存在parkin基因的突变.

  15. Gingival Recession: Review and Strategies in Treatment of Recession

    OpenAIRE

    Koppolu Pradeep; Palaparthy Rajababu; Durvasula Satyanarayana; Vidya Sagar

    2012-01-01

    One of the most common esthetic concerns associated with the periodontal tissues is gingival recession. Gingival recession is the exposure of root surfaces due to apical migration of the gingival tissue margins; gingival margin migrates apical to the cementoenamel junction. Although it rarely results in tooth loss, marginal tissue recession is associated with thermal and tactile sensitivity, esthetic complaints, and a tendency toward root caries. This paper reviews etiology, consequences, and...

  16. Escaping the Great Recession

    OpenAIRE

    Bianchi, Francesco; Melosi, Leonardo

    2013-01-01

    While high uncertainty is an inherent implication of entering the zero lower bound, deflation is not, because agents are likely to be uncertain about the way policy makers will deal with the large stock of debt arising from a severe recession. We draw this conclusion based on a standard new-Keynesian model in which policy makers' behavior can move between a Monetary and a Fiscally led regime and zero lower bound episodes are recurrent. Given that policy makers' behavior is constrained at the ...

  17. Experience of a single center with congenital hepatic fibrosis:A review of the literature

    Institute of Scientific and Technical Information of China (English)

    Ali; Shorbagi; Yusuf; Bayraktar

    2010-01-01

    Congenital hepatic fibrosis(CHF) is an autosomal recessive inherited malformation defined pathologically by a variable degree of periportal fibrosis and irregularly shaped proliferating bile ducts.It is one of the fibropolycystic diseases,which also include Caroli disease,autosomal dominant polycystic kidney disease,and autosomal recessive polycystic kidney disease. Clinically it is characterized by hepatic fibrosis,portal hypertension,and renal cystic disease.CHF is known to occur in association with a ran...

  18. Caroli′s syndrome in a post renal transplant patient: Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Muhammad Z Bawany

    2012-01-01

    Full Text Available Caroli′s syndrome is characterized by bile duct ectasia in association with hepatic fibrosis. It is usually transmitted in an autosomal recessive fashion and has been well documented to be associated with autosomal recessive polycystic kidney disease and occasionally with autosomal dominant polycystic kidney disease. However, there has been only few case reports published with Caroli′s syndrome diagnosed postrenal transplantation.

  19. Experience of a single center with congenital hepatic fibrosis: A review of the literature

    OpenAIRE

    Shorbagi, Ali; Bayraktar, Yusuf

    2010-01-01

    Congenital hepatic fibrosis (CHF) is an autosomal recessive inherited malformation defined pathologically by a variable degree of periportal fibrosis and irregularly shaped proliferating bile ducts. It is one of the fibropolycystic diseases, which also include Caroli disease, autosomal dominant polycystic kidney disease, and autosomal recessive polycystic kidney disease. Clinically it is characterized by hepatic fibrosis, portal hypertension, and renal cystic disease. CHF is known to occur in...

  20. Unemployment in the great recession

    OpenAIRE

    Christopher A. Pissarides

    2013-01-01

    This paper studies the responses of unemployment in Germany, the United States and Britain to the Great Recession of 2008-09 by making use of Beveridge curve analysis, and in the entire OECD with other techniques. It is shown that Britain suffered from recession but no structural problems; the United States suffered from structural unemployment during the recovery; Germany exhibited a much better performance both during and after the recession. The rise in OECD unemployment is broken down int...

  1. Crises and the Great Recession

    OpenAIRE

    Tatom, John A.

    2013-01-01

    The U.S. economy suffered in 2007–10 from crises in mortgage foreclosures and in financial markets, as well as a long recession that some have referred to as the Great Recession. The links between these events, or more broadly their causes, extent, and effects are sources of continuing controversy and uncertainty. This paper attempts to disentangle the links between the mortgage foreclosure crisis, the financial crisis, a possible banking crisis, and the Great Recession, at least in terms of ...

  2. Generation recession? How the recession may change America

    OpenAIRE

    Mark S. Sniderman

    2011-01-01

    Nobody yet knows the ultimate footprint that the Great Recession will have on the nation. We do know that much of it depends on the choices that Americans make in response—everything from personal saving to labor force participation is in play. Ultimately, these choices will help determine how “great” the recession really turns out to be.

  3. Polycystic Ovary Syndrome in Adolescents.

    Science.gov (United States)

    Witchel, Selma Feldman; Roumimper, Hailey; Oberfield, Sharon

    2016-06-01

    Polycystic ovary syndrome (PCOS) is a familial heterogeneous disorder affecting 6% to 10% of reproductive-age women. The use of criteria developed for adult women is problematic for the adolescent girl because the clinical features associated with PCOS are normal pubertal events. The recent consensus statement on PCOS in adolescents stated that hyperandrogenism and oligomenorrhea need to persist for at least 2 years to consider the diagnosis of PCOS. Although insulin resistance, hyperinsulinism, and obesity are often associated with PCOS, these features are not considered valid diagnostic criteria. Recent genomewide association studies implicate genetic loci involved in the hypothalamic-pituitary-ovarian axis. PMID:27241968

  4. STATINS IN POLYCYSTIC OVARY SYNDROME

    Directory of Open Access Journals (Sweden)

    P. S. Patel*, T. D. Goswami, A. D. Sharma and B. S. Arora

    2012-11-01

    Full Text Available Polycystic ovary syndrome (PCOS is the most common endocrine disorder in women. PCOS varies from a mild menstrual disorder to severe disturbance of reproductive and metabolic functions. Statins, 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA reductase inhibitors with intrinsic antioxidant properties, exert profound and broad-reaching effects on various types of tissues. By blocking an early step of the mevalonate pathway, statins inhibit proliferation of several cell types including vascular smooth muscles, hepatocytes, and several neoplastic cell lines. The pleiotropic effects of statins may be due to inhibition of cholesterol synthesis. Some common treatments lifestyle changes, insulin-sensitizing agents.

  5. THE RECESSING DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    MARINA LUMINITA SARBOVAN

    2012-05-01

    Full Text Available For some decades now, the social attention in our country and Europe focused on the ecological part of sustainable economy. Even now, the attention is focused on the foreign debt crisis, fiscal and monetary macroeconomic plans and measures being the most prominent part of the European economic policy. The follow up of this reality is that the rising employment long term goal of European Union did not get a spectacular achievement, in terms of rising employment and diminishing unemployment, as well. Close tied to the European evolution, our country crosses a recessing development because, given the current national effects of the austerity that we all have to face and determined by the global crisis, the economic output measured by GDP is raising, even in such conditions.

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

    Directory of Open Access Journals (Sweden)

    Bosl William J

    2010-06-01

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

  7. Morphologic,mechanical and functional sonographic parameters of arteries in autosomal dominant polycystic kidney disease

    Institute of Scientific and Technical Information of China (English)

    戎殳

    2006-01-01

    Objective To investigate whether the risk factors of cardiovascular disease exist in early stage of ADPKD patients with normal renal function. Methods Morphologic , mechanical and functional sonographic parameters of arteries were examined by high-frequency ultrasonography in 32 hypertensive and 28 normotensive ADPKD patients with preserved renal function, 25 patients with es-

  8. Asymmetric dimethylarginine and lipid peroxidation products in early autosomal dominant polycystic kidney disease

    DEFF Research Database (Denmark)

    Wang, Dan; Strandgaard, S.; Borresen, M.L.;

    2008-01-01

    nitric oxide synthase and the lipid peroxidation product 13-hydroxyoctadecadienoic acid (HODE) as a marker of oxidative stress in patients with early ADPKD. Study Design: Cross-sectional study. Setting & Participants: Patients with early ADPKD (n = 27) and age-matched volunteers (n = 30) from a single...... academic medical center. Factor: Patients with ADPKD versus controls. Outcomes & Measurement: Plasma (P) levels, urinary (U) excretion, and urinary clearance (C) of ADMA and HODE. Because of multiple comparisons, P for significance is considered less than 0.0167. Results: Patients with ADPKD had......-sectional nature of study, and limited number of markers of oxidative stress. Conclusions: P-ADMA and P-HODE levels are increased in patients with early ADPKD. Increased P-ADMA level is related to decreased CADMA and is accompanied by oxidative stress. Am J Kidney Dis 51:184-191. (c) 2008 by the National Kidney...

  9. Potential Deleterious Effects of Vasopressin in Chronic Kidney Disease and Particularly Autosomal Dominant Polycystic Kidney Disease

    NARCIS (Netherlands)

    Meijer, E.; Boertien, W. E.; Zietse, R.; Gansevoort, R. T.

    2011-01-01

    The antidiuretic hormone vasopressin is crucial for regulating free water clearance in normal physiology. However, it has also been hypothesized that vasopressin has deleterious effects on the kidney. Vasopressin is elevated in animals and patients with chronic kidney disease. Suppression of vasopre

  10. Polycystic ovarian syndrome in identical twins.

    OpenAIRE

    Hutton, C.; Clark, F.

    1984-01-01

    Two 21-year-old female twins are described. They presented simultaneously with hirsutism and oligomenorrhoea. Investigation showed they had polycystic ovaries, they were identical and were not cases of post-pubertal adrenogenital syndrome.

  11. Polycystic ovary syndrome: from phenotype to genetype

    NARCIS (Netherlands)

    Y.V. Louwers (Yvonne)

    2014-01-01

    markdownabstract__Abstract__ oligomenorrhea or amenorrhea, hirsutism or hyperandrogenism and polycystic ovarian morphology. Later in life, adverse metabolic implications, such as obesity, insulin resistance, type 2 diabetes and cardiovascular disease, become more prominent. In this thesis, we aimed

  12. Bilateral Parotid Swelling in Polycystic Ovarian Syndrome.

    Science.gov (United States)

    Yakubov, Yakov; Mandel, Louis

    2016-05-01

    Polycystic ovarian syndrome (PCOS) is recognized by the presence of polycystic ovaries, irregular menstruation, and increased androgen levels. Many patients have insulin resistance or impaired glucose tolerance and an associated development of type 2 diabetes mellitus. A patient with PCOS is presented whose cosmetic concerns centered on the prolonged existence of substantial bilateral parotid swelling. The pathophysiology, diagnosis, and therapy of sialosis are discussed. PMID:26657398

  13. Polycystic Ovary Syndrome - diagnosis and treatment

    OpenAIRE

    Hussain, Amna

    2015-01-01

    Abstract: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder, and a major cause of infertility in women. An excessive amount of androgen hormones are produced by polycystic ovaries in PCOS with irregular menstruation and anovulation as result. The most common early symptoms are infertility, hirsutism and acne. Type 2 diabetes mellitus, metabolic syndrome, and possibly cardiovascular disease and endometrial carcinoma are all associated as lifelong implications with t...

  14. Women's Health Implications of Polycystic Ovary Syndrome

    OpenAIRE

    Veltman-Verhulst, S.M.

    2012-01-01

    Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder of unknown etiology which affects approximately 12% of women. Principal features of PCOS are anovulation resulting in irregular or absent menstruation, excessive androgens (male sex hormones) and ovaries with multiple follicles (polycystic ovaries). PCOS has been associated with a variety of health complications of reproductive, metabolic, and psychological nature. Although PCOS is predominantly diagnosed in women of reproductiv...

  15. Recessive omodysplasia: five new cases and review of the literature

    International Nuclear Information System (INIS)

    Autosomal recessive omodysplasia (MIM 258315) is a rare skeletal dysplasia characterized by severe congenital micromelia with shortening and distal tapering of the humeri and femora to give a club-like appearance. Fewer than 20 cases have been reported in the literature so far. The purpose of this study was to more clearly describe the clinical and radiographic phenotypes and their changes with age. Five new patients, including two sibs, with autosomal recessive omodysplasia are presented. Clinical features are rhizomelic dwarfism with limited extension of elbows and knees and a distinct face with a short nose, depressed nasal bridge, long philtrum, midline haemangiomas in infants and cryptorchidism in males. Radiological findings are distal hypoplasia of the short humerus and femur with characteristic radial dislocation and radioulnar diastasis. Based on a review of these and 16 previously reported patients, the regressive nature of the humerofemoral changes and the obvious male predominance are stressed. Phenotypic similarities with the atelosteogenesis group of disorders and with diastrophic dysplasia suggest common pathogenetic mechanisms. (orig.)

  16. Seruin lipoprotein (a) levels in patients with polycystic ovarian disease

    OpenAIRE

    Kafkaslı, Dr. Ayşe; Akbaşak, Dr. Bülbin S.; Buhur, Dr. Ali; Turan, Bio. Fahri

    1996-01-01

    Lipoprotein (a) levels were studied in 5 patients whose biochemical and transvaginal ultrasonographic findings were consistent with polycystic ovarian syndrome. Eleveted serum lipoprotein (a) levels were detected in 4 out of 5 patients. Keywords: Polycystic ovarian disease, lipoprotein (a)

  17. Copper : recession and recovery

    International Nuclear Information System (INIS)

    In 2002, the world output for copper will fall for the first time in nearly a decade because of financial pressure and voluntary constraints. Cutbacks at copper mines amount to 760,000 tonnes per year. These cutbacks have occurred mostly in the United States which holds the largest share of high cost mines. This paper discussed recent developments in both copper supply and demand. The United States is unique as both a large consumer and producer of copper. At 1.35 million tonnes, US mine output in 2001 was at its lowest since 1987. The cutbacks in mining in general were described in this paper with particular reference to the huge loss of mining and metallurgical activity in the United States during a prolonged period of low prices in the mid 1980s. The author noted that this period was followed by an exceptional decade when much of the industry rebounded. Only 8 mines closed outright in the United States and a handful in Canada since the recession of the 1980s, but that is partly because mines got bigger and there are fewer small mines in North America. There are only 4 electrolytic refineries and 3 smelters still active in the entire United States, of which 2 are operating at a fraction of capacity. It was noted that only the buoyancy of China prevented a much bigger decline in copper demand on a global scale

  18. What Caused the Great Recession?

    OpenAIRE

    Homburg, Stefan

    2014-01-01

    This paper examines five possible explanations for the Great Recession of 2008 and 2009, using data for the United States and the eurozone. Of these five hypotheses, four are not supported by the data, while the fifth appears reasonable.

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

    OpenAIRE

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

    2006-01-01

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

  20. Whole Exome Sequencing Identifies Recessive PKHD1 Mutations in a Chinese Twin Family with Caroli Disease

    OpenAIRE

    Hao, Xiwei; Liu, Shiguo; Dong, Qian; Zhang, Hong; Zhao, Jing; Su, Lin

    2014-01-01

    Background Mutations in PKHD1 cause autosomal recessive Caroli disease, which is a rare congenital disorder involving cystic dilatation of the intrahepatic bile ducts. However, the mutational spectrum of PKHD1 and the phenotype-genotype correlations have not yet been fully established. Methods Whole exome sequencing (WES) was performed on one twin sample with Caroli disease from a Chinese family from Shandong province. Routine Sanger sequencing was used to validate the WES and to carry out se...

  1. A Great Recession in economics?

    OpenAIRE

    Sergio Da Silva

    2012-01-01

    The number of downloads of economics articles through the repository RePEc showed a sharp drop on the eve of the Great Recession in the economy. This unambiguously occurred with the Blue Ribbon journals, but can possibly be extended to other important journals. If we can perhaps talk of a great recession in economics, in the sense of a general lack of interest in reading economics papers, this may have been part of the overall bearish mood of the time.

  2. Uncertainty and the Great Recession

    OpenAIRE

    Born, Benjamin; Breuer, Sebastian; Elstner, Steffen

    2014-01-01

    Has heightened uncertainty been a major contributor to the Great Recession and the slow recovery in the U.S.? To answer this question, we identify exogenous changes in six uncertainty proxies and quantify their contributions to GDP growth and the unemployment rate. Our results are threefold. First, only a minor part of the rise in uncertainty measures during the Great Recession was driven by exogenous uncertainty shocks. Second, while increased uncertainty explains less than one percentage po...

  3. Combating automative engine valve recession

    OpenAIRE

    Lewis, R; Dwyer-Joyce, R.S.

    2003-01-01

    [INTRODUCTION] Valve recession occurs when wear of the valve or seat inserts in an automotive engine has caused the valve to sink or recede into the seat insert (as shown in Figure 1). Excessive recession leads to valves not seating correctly and cylinder pressure loss. Leaking hot combustion gases can also cause valve guttering or torching, which will accelerate valve failure. Although new valve materials and production techniques are constantly being developed, these advances h...

  4. Crises and the recent recession

    OpenAIRE

    Tatom, John

    2010-01-01

    The United States economy has suffered over the past four years from crises in mortgage foreclosures and in financial markets, as well as a long recession that some have referred to as the Great Recession. The links between these events, or more broadly the causes, extent and effects of these developments, are sources of continuing controversy and uncertainty. This paper attempts to disentangle the links between the mortgage foreclosure crisis, the financial crisis, a possible banking crisis ...

  5. Laminin 5 regulates polycystic kidney cell proliferation and cyst formation.

    Science.gov (United States)

    Joly, Dominique; Berissi, Sophie; Bertrand, Amélie; Strehl, Laetitia; Patey, Natacha; Knebelmann, Bertrand

    2006-09-29

    Renal cyst formation is the hallmark of autosomal dominant polycystic kidney disease (ADPKD). ADPKD cyst-lining cells have an increased proliferation rate and are surrounded by an abnormal extracellular matrix (ECM). We have previously shown that Laminin 5 (Ln-5, a alpha(3)beta(3)gamma(2) trimer) is aberrantly expressed in the pericystic ECM of ADPKD kidneys. We report that ADPKD cells in primary cultures produce and secrete Ln-5 that is incorporated to the pericystic ECM in an in vitro model of cystogenesis. In monolayers, purified Ln-5 induces ERK activation and proliferation of ADPKD cells, whereas upon epidermal growth factor stimulation blocking endogenously produced Ln-5 with anti-gamma(2) chain antibody reduces the sustained ERK activation and inhibits proliferation. In three-dimensional gel culture, addition of purified Ln-5 stimulates cell proliferation and cyst formation, whereas blocking endogenous Ln-5 strongly inhibits cyst formation. Ligation of alpha(6)beta(4) integrin, a major Ln-5 receptor aberrantly expressed by ADPKD cells, induces beta(4) integrin phosphorylation, ERK activation, cell proliferation, and cyst formation. These findings indicate that Ln-5 is an important regulator of ADPKD cell proliferation and cystogenesis and suggest that Ln-5 gamma(2) chain and Ln-5-alpha(6)beta(4) integrin interaction both contribute to these phenotypic changes. PMID:16870608

  6. Mutations in BRAT1 cause autosomal recessive progressive encephalopathy: Report of a Spanish patient

    Science.gov (United States)

    Fernández-Jáen, Alberto; Álvarez, Sara; So, Eui Young; Ouchi, Toru; de la Peña, Mar Jiménez; Duat, Anna; Fernández-Mayoralas, Daniel Martín; Fernández-Perrone, Ana Laura; Albert, Jacobo; Calleja-Pérez, Beatriz

    2016-01-01

    We describe a 4-year-old male child born to non-consanguineous Spanish parents with progressive encephalopathy (PE), microcephaly, and hypertonia. Whole exome sequencing revealed compound heterozygous BRAT1 mutations [c.1564G > A (p.Glu522Lys) and c.638dup (p.Val214Glyfs*189)]. Homozygous and compound heterozygous BRAT1 mutations have been described in patients with lethal neonatal rigidity and multifocal seizure syndrome (MIM# 614498). The seven previously described patients suffered from uncontrolled seizures, and all of those patients died in their first months of life. BRAT1 acts as a regulator of cellular proliferation and migration and is required for mitochondrial function. The loss of these functions may explain the cerebral atrophy observed in this case of PE. This case highlights the extraordinary potential of next generation technologies for the diagnosis of rare genetic diseases, including PE. Making a prompt diagnosis of PE is important for genetic counseling and disease management. PMID:26947546

  7. Loss-of-Function Mutations in HPSE2 Cause the Autosomal Recessive Urofacial Syndrome

    OpenAIRE

    Pang, Junfeng; Zhang, Shu; Yang, Ping; Hawkins-Lee, Bobbilynn; Zhong, Jixin; Zhang, Yushan; Ochoa, Bernardo; Agundez, Jose A.G.; Voelckel, Marie-Antoinette; Fisher, Richard B; Gu, Weikuan; Xiong, Wen-Cheng; Mei, Lin; She, Jin-Xiong; Wang, Cong-Yi

    2010-01-01

    Previously, we localized the defective gene for the urofacial syndrome (UFS) to a region on chromosome 10q24 by homozygosity mapping. We now report evidence that Heparanse 2 (HPSE2) is the culprit gene for the syndrome. Mutations with a loss of function in the Heparanase 2 (HPSE2) gene were identified in all UFS patients originating from Colombia, the United States, and France. HPSE2 encodes a 592 aa protein that contains a domain showing sequence homology to the glycosyl hydrolase motif in t...

  8. Homozygous mutation of STXBP5L explains an autosomal recessive infantile-onset neurodegenerative disorder

    NARCIS (Netherlands)

    Kumar, R.; Corbett, M.A.; Smith, N.J.; Jolly, L.A.; Tan, C.; Keating, D.J.; Duffield, M.D.; Utsumi, T.; Moriya, K.; Smith, K.R.; Hoischen, A.; Abbott, K.; Harbord, M.G.; Compton, A.G.; Woenig, J.A.; Arts, P.; Kwint, M.; Wieskamp, N.; Gijsen, S.; Veltman, J.A.; Bahlo, M.; Gleeson, J.G.; Haan, E.; Gecz, J.

    2015-01-01

    We report siblings of consanguineous parents with an infantile-onset neurodegenerative disorder manifesting a predominant sensorimotor axonal neuropathy, optic atrophy and cognitive deficit. We used homozygosity mapping to identify an approximately 12-Mbp interval identical by descent (IBD) between

  9. Genetic dissection of two Pakistani families with consanguineous localized autosomal recessive hypotrichosis (LAH

    Directory of Open Access Journals (Sweden)

    Seyyedha Abbas

    2014-07-01

    Conclusion:Both families were tested for linkage by genotyping polymorphic microsatellite markers linked to known alopecia loci. Family A excluded all known diseased regions that is suggestive of some novel chromosomal disorder. However, sequencing of P2RY5 gene in family B showed no pathogenic mutation.

  10. "Dermatoglyphic Observations in an Iranian Girl Affected with Congenital Cutis Laxa (Autosomal Recessive"

    Directory of Open Access Journals (Sweden)

    H Pour-Jafari

    2003-08-01

    Full Text Available The aim of the this work was to determine the finger patterns, Finger Ridge Count (FRC, Total Finger Ridge Count (TFRC, and Asymmetry of Finger Ridge Count (AFRC of an Iranian girl (aged 13 years affected with congenital cutis laxa (CCL.The fingerprints of the first phalanx of both hands were taken by using the standard method (stamp ink. The fingerprints were classified according to the Galton nomenclature. The patterns of palm creases were also studied. Besides, the ridges of fingerprints of all ten fingers were counted, then employing the related formulas, the FRC, TFRC and AFRC were calculated.Results showed that the finger patterns of all ten fingers were radial loop; the major creases of the palms existed but their sizes were not normal. TFRC, which is the sum of all ten FRCs, was 77 (“low”, and AFRC was 10.344, more than that of her normal sister, that was 7.280. It is concluded that in CCL, the TFRC and symmetry of the fingertips ridges count may decrease; also palm pattern may be unusual.

  11. A newly recognized autosomal recessive syndrome affecting neurologic function and vision

    OpenAIRE

    Salih, M.; A. Tzschach; Oystreck, D.; Hassan, H.; AlDrees, A.; Elmalik, S.; El Khashab, H.; Wienker, T; Abu-Amero, K; Bosley, T.

    2013-01-01

    Genetic factors represent an important etiologic group in the causation of intellectual disability. We describe a Saudi Arabian family with closley related parents in which four of six children were affected by a congenital cognitive disturbance. The four individuals (aged 18, 16, 13, and 2 years when last examined) had motor and cognitive delay with seizures in early childhood, and three of the four (sparing only the youngest child) had progressive, severe cognitive decline with spasticity. ...

  12. Familial carnitine deficiency: further evidence for autosomal recessive transmission with variable expression.

    OpenAIRE

    Shahar, E.; Brand, N; Shapira, Y.; Barash, V; Gutman, A

    1988-01-01

    Carnitine deficiency occurring in families has been rarely reported and the genetic transmission has not yet been clearly elucidated. Five members of one family showing marked heterogeneity of carnitine deficiency states are presented. In three patients, there was no correlation between measurable carnitine levels in serum and muscle and the clinical findings. The parents, who are remote relatives from an isolated village in Kurdistan (Iraq), had low muscle carnitine levels; however, they wer...

  13. Vici Syndrome: A Rare Autosomal Recessive Syndrome with Brain Anomalies, Cardiomyopathy, and Severe Intellectual Disability

    Directory of Open Access Journals (Sweden)

    R. Curtis Rogers

    2011-01-01

    Full Text Available Purpose. The objective of this study was to present and describe two additional patients diagnosed with Vici syndrome. Methods. Clinical, laboratory, and imaging findings of the two siblings are discussed in detail. The two patients' descriptions are compared with the other eleven patients reported in the literature. We also presented detailed autopsy results on the male sibling, which demonstrated cytoplasmic vacuoles of the cardiomyocytes and confirmed the clinical findings. Results. The patients reported here include the 13th and 14th patients reported with Vici syndrome. The summary of findings present in these patients includes postnatal growth retardation, developmental delay, bilateral cataracts, agenesis of the corpus callosum, cerebellar anomalies, gyral abnormalities, seizures, hypotonia, and cardiomyopathy. Conclusion. Vici syndrome should be suspected in any child with agenesis of the corpus callosum and one of the following findings: cardiomyopathy, cataracts, immune deficiency, or cutaneous hypopigmentation.

  14. Aquaporin-2: new mutations responsible for autosomal-recessive nephrogenic diabetes insipidus—update and epidemiology

    OpenAIRE

    Bichet, Daniel G.; El Tarazi, Abdulah; Matar, Jessica; Lussier, Yoann; Arthus, Marie-Françoise; Lonergan, Michèle; Bockenhauer, Detlef; Bissonnette, Pierre

    2012-01-01

    It is clinically useful to distinguish between two types of hereditary nephrogenic diabetes insipidus (NDI): a ‘pure’ type characterized by loss of water only and a complex type characterized by loss of water and ions. Patients with congenital NDI bearing mutations in the vasopressin 2 receptor gene, AVPR2, or in the aquaporin-2 gene, AQP2, have a pure NDI phenotype with loss of water but normal conservation of sodium, potassium, chloride and calcium. Patients with hereditary hypokalemic salt...

  15. Macrocephaly, epilepsy, autism, dysmorphic features, and mental retardation in two sisters: a new autosomal recessive syndrome?

    OpenAIRE

    Orstavik, K H; Strømme, P; van Ek, J.; Torvik, A; Skjeldal, O H

    1997-01-01

    We report two sisters with macrocephaly, epilepsy, and severe mental retardation. The first child was a 14 year old girl born at term after a normal pregnancy, with birth weight 3600 g and occipitofrontal circumference (OFC) 36 cm (75th centile). Her head size increased markedly during the first six months of life, and was later stable at 2-3 cm above the 97.5th centile. Her development was characterised by psychomotor delay, epilepsy, and autistic features. Her face appeared mildly dysmorphi...

  16. CLPB Variants Associated with Autosomal-Recessive Mitochondrial Disorder with Cataract, Neutropenia, Epilepsy, and Methylglutaconic Aciduria

    DEFF Research Database (Denmark)

    Saunders, Carol; Smith, Laurie; Wibrand, Flemming;

    2015-01-01

    type IV 3-MGA-uria characterized by cataracts, severe psychomotor regression during febrile episodes, epilepsy, neutropenia with frequent infections, and death in early childhood. Four of the individuals were of Greenlandic descent, and one was North American, of Northern European and Asian descent...

  17. FBXO7 mutations cause autosomal recessive, early-onset parkinsonian-pyramidal syndrome.

    NARCIS (Netherlands)

    Fonzo, A. Di; Dekker, M.C.J.; Montagna, P.; Baruzzi, A.; Yonova, E.H.; Correia Guedes, L.; Szczerbinska, A.; Zhao, T.; Dubbel-Hulsman, L.O.; Wouters, C.H.; Graaff, E. de; Oyen, W.J.G.; Simons, E.J.; Breedveld, G.J.; Oostra, B.A.; Horstink, M.W.I.M.; Bonifati, V.

    2009-01-01

    BACKGROUND: The combination of early-onset, progressive parkinsonism with pyramidal tract signs has been known as pallido-pyramidal or parkinsonian-pyramidal syndrome since the first description by Davison in 1954. Very recently, a locus was mapped in a single family with an overlapping phenotype, a

  18. Genetics Home Reference: cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy

    Science.gov (United States)

    ... Miyashita A, Yokoseki A, Kawata H, Koyama A, Arima K, Takahashi T, Ikeda M, Shiota H, Tamura ... Oide T, Nakayama H, Yanagawa S, Ito N, Ikeda S, Arima K. Extensive loss of arterial medial smooth muscle ...

  19. Valproate, bipolar disorder and polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    Okanović Milana

    2016-01-01

    Full Text Available Introduction. Polycystic ovarian syndrome is a syndrome of ovarian dysfunction with the principal features of hyperandrogenism and polycystic ovary morphology. A large number of studies conducted on this topic have suggested a possible role of anticonvulsants, particularly valproate, in the pathogenesis or risk factors associated with polycystic ovarian syndrome. Bipolar treatment guidelines from Canada and the United States of America recommend valproate as the first line strategy in the acute treatment of bipolar disorder. Discussion. Most persons with bipolar disorder require maintenance treatment. Long-term administration of valproate in women with bipolar disorder or epilepsy is believed to result in the increased risk of hyperandro­genism, menstrual abnormalities and polycystic ovaries. Valproate may also increase the risk of infertility and other associated symptoms of polycystic ovarian syndrome. Therefore, particular caution is indicated in the use of valproate in women of reproductive age. Conclusion. The treatment of the female patients with bipolar disorder presents various challenges for the clinician. Every woman of reproductive age needs to know the risk and benefits of her pharmacologic treatment options. Bipolar disorder should be considered chronic disorder, whose development is largely affected by hormonal changes and reproductive cycle in women. These issues should be researched more thoroughly in order to opt for the most appropriate treatment in women with bipolar disorder.

  20. The Great Recession was not so Great

    OpenAIRE

    van Ours, J.C.

    2015-01-01

    The Great Recession is characterized by a GDP-decline that was unprecedented in the past decades. This paper discusses the implications of the Great Recession analyzing labor market data from 20 OECD countries. Comparing the Great Recession with the 1980s recession it is concluded that there is a high cross-country correlation of the unemployment rates over the two recessions indicating that some labor markets are more vulnerable to fluctuations in economic growth than others. Young workers a...

  1. UAB HRFD Core Center: Core A: The Hepato/Renal Fibrocystic Diseases Translational Resource

    Science.gov (United States)

    2016-01-26

    Hepato/Renal Fibrocystic Disease; Autosomal Recessive Polycystic Kidney Disease; Joubert Syndrome; Bardet Biedl Syndrome; Meckel-Gruber Syndrome; Congenital Hepatic Fibrosis; Caroli Syndrome; Oro-Facial-Digital Syndrome Type I; Nephronophthisis; Glomerulocystic Kidney Disease

  2. Genetics Home Reference: autosomal dominant vitreoretinochoroidopathy

    Science.gov (United States)

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

  3. Diagnosis and Treatment of Polycystic Ovary Syndrome.

    Science.gov (United States)

    Williams, Tracy; Mortada, Rami; Porter, Samuel

    2016-07-15

    Polycystic ovary syndrome is the most common endocrinopathy among reproductive-aged women in the United States, affecting approximately 7% of female patients. Although the pathophysiology of the syndrome is complex and there is no single defect from which it is known to result, it is hypothesized that insulin resistance is a key factor. Metabolic syndrome is twice as common in patients with polycystic ovary syndrome compared with the general population, and patients with polycystic ovary syndrome are four times more likely than the general population to develop type 2 diabetes mellitus. Patient presentation is variable, ranging from asymptomatic to having multiple gynecologic, dermatologic, or metabolic manifestations. Guidelines from the Endocrine Society recommend using the Rotterdam criteria for diagnosis, which mandate the presence of two of the following three findings- hyperandrogenism, ovulatory dysfunction, and polycystic ovaries-plus the exclusion of other diagnoses that could result in hyperandrogenism or ovulatory dysfunction. It is reasonable to delay evaluation for polycystic ovary syndrome in adolescent patients until two years after menarche. For this age group, it is also recommended that all three Rotterdam criteria be met before the diagnosis is made. Patients who have marked virilization or rapid onset of symptoms require immediate evaluation for a potential androgen-secreting tumor. Treatment of polycystic ovary syndrome is individualized based on the patient's presentation and desire for pregnancy. For patients who are overweight, weight loss is recommended. Clomiphene and letrozole are first-line medications for infertility. Metformin is the first-line medication for metabolic manifestations, such as hyperglycemia. Hormonal contraceptives are first-line therapy for irregular menses and dermatologic manifestations. PMID:27419327

  4. Barriers for recess physical activity

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Tjørnhøj-Thomsen, Tine; Schipperijn, Jasper;

    2014-01-01

    ) with in total 111 children (53 boys) from fourth grade, with a mean age of 10.4 years. The focus groups included an open group discussion, go-along group interviews, and a gender segregated post-it note activity. A content analysis of the post-it notes was used to rank the children's perceived barriers......BACKGROUND: Many children, in particular girls, do not reach the recommended amount of daily physical activity. School recess provides an opportunity for both boys and girls to be physically active, but barriers to recess physical activity are not well understood. This study explores gender...... differences in children's perceptions of barriers to recess physical activity. Based on the socio-ecological model four types of environmental barriers were distinguished: natural, social, physical and organizational environment. METHODS: Data were collected through 17 focus groups (at 17 different schools...

  5. The Great Recession: a comparison of recession magnitudes in Europe, USA and Japan

    OpenAIRE

    Mazurek, Jiří

    2013-01-01

    In this article recession magnitudes in Europe, the USA and Japan during the Great Recession are compared. The strongest recessions (of severe category) occurred in Latvia, Lithuania and Estonia, while recessions in Japan and the USA were significantly weaker. Even the strongest recession (in Latvia) was found smaller in its magnitude than the Great Depression 1929-1933 in the USA. Hence, comparisons of the Great Recession to the Great Depression in the literature are somewhat exaggerated.

  6. Noncompaction of the Ventricular Myocardium and Polycystic Kidney Disease: A Case Report.

    Science.gov (United States)

    Fukino, Keiko; Ishiwata, Junpei; Shinohara, Hiroki; Oshima, Tsukasa; Kozaki, Tsunashi; Ikutomi, Masayasu; Amaki, Toshihiro; Nakamura, Fumitaka

    2016-06-01

    Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary disorders, characterized by the formation of multiple cysts in the kidneys and other organs, as well as noncystic manifestations such as cerebral aneurysm. The most common cardiovascular disorders associated with ADPKD include valvular abnormalities and aortic aneurysm. An association between ADPKD and impaired left ventricular function has occasionally been reported. We describe a 74-year-old woman with ADPKD and exertional dyspnea. Impaired left ventricular function resulting from noncompaction of the ventricular myocardium (NVM) and secondary left ventricular aneurysm were diagnosed. Cardiac sarcoidosis and ischemic heart disease were ruled out. Myocardial ischemia resulting from NVM was the presumptive cause of the ventricular aneurysm. To our knowledge, this is the first report of concurrent isolated NVM and left ventricular aneurysm in a patient with ADPKD. ADPKD and various cardiomyopathies, including NVM, are all reported to involve mutations of sarcomere genes, suggesting a possible link between the conditions. PMID:26873255

  7. Overexpression of Aquaporin 1 on cysts of patients with polycystic liver disease

    Directory of Open Access Journals (Sweden)

    Li Dingyang

    2016-02-01

    Full Text Available Background and objective: Polycystic liver disease (PCLD represents a group of genetic disorders that include autosomal dominant polycystic kidney disease (ADPKD and isolated polycystic liver disease (iPCLD. There is currently no definitive treatment except for liver transplantation. The aim of this study was to assess the expression level of aquaporin 1 (AQP1 on the PCLD cysts with different sizes and provide the potential therapeutic target. Methods: We collected 3 normal bile ducts, and recruited 8 patients with simple liver cyst disease, 24 patients with ADPKD, and 17 patients with iPCLD. AQP1 expression in different types of cyst walls and in normal bile ducts was detected using real time quantitative PCR, western blot and immunofluorescence staining. We also compared AQP1 expression levels in cysts of different sizes. Besides, ionic concentrations, pH and osmolality of cyst fluid were analyzed. Results: The results showed that AQP1 expression in PCLD cysts was significantly higher than that in simple liver cysts and the normal bile ducts. In addition, a comparable increasing trend was found in cysts of smaller sizes to cysts of larger sizes. pH values, the sodium and chloride concentrations were higher in cyst fluid than that in the serum. Conclusions: AQP1 was overexpressed in cystic cholangiocytes. A tendency of increased AQP1 protein expression in correlation with the cyst size was also found. These observations offered a direction into the molecular mechanisms of cyst expansion and maybe provide new treatment strategies to reduce fluid secretion into liver cysts.

  8. Algebra, Home Mortgages, and Recessions

    Science.gov (United States)

    Mariner, Jean A. Miller; Miller, Richard A.

    2009-01-01

    The current financial crisis and recession in the United States present an opportunity to discuss relevant applications of some topics in typical first-and second-year algebra and precalculus courses. Real-world applications of percent change, exponential functions, and sums of finite geometric sequences can help students understand the problems…

  9. Firms Still Training Despite Recession

    Science.gov (United States)

    Felstead, Alan; Green, Francis; Jewson, Nick

    2011-01-01

    It is commonly assumed that company training is one of the first casualties in times of recession. Falling recruitment, pressures to cut costs and a focus on short-term survival force businesses to put training on the backburner. Expecting the worst, the UK Commission for Employment and Skills (UKCES), the Confederation of British Industry (CBI)…

  10. Oncological repercussions of polycystic ovary syndrome

    DEFF Research Database (Denmark)

    de França Neto, Antônio H; Rogatto, Silvia; Do Amorim, Melania M R;

    2010-01-01

    Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine disorder that has been associated with insulin resistance and metabolic syndrome. Evidence has suggested that PCOS may be associated with the appearance of certain types of cancer, particularly endometrial, ovarian and breast cancer...

  11. Complementary Therapy in Polycystic Ovary Syndrome

    OpenAIRE

    Aquino, Carmen Imma; Nori, Stefania Lucia

    2014-01-01

    Polycystic Ovary Syndrome (PCOS) is an endocrine disease. PCOS afflicts 5 to 10 % of women of reproductive age. The symptoms are: amenorrhea, oligomenorrhea, hirsutism, obesity, infertility, chronic hyperandrogenic anovulation and acne. Other risk factors aggravate this condition: insulin resistance, obesity, hypertension, dyslipidemia, inflammation and subclinical cardiovascular disease. Anxiety, depression and reduced quality of life are also common. This review highlights the mechanisms an...

  12. Polycystic liver transplant: a case report.

    Science.gov (United States)

    Sakcak, Ibrahim; Olmez, Aydemir; Ozgor, Dincer; Eris, Cengiz; Kayaalp, Cuneyt; Yılmaz, Sezai

    2013-06-01

    A liver from a donor with brain death due to a ruptured cerebral aneurysm was transplanted. The liver had multiple bilobar simple cysts; the largest was less than 3 cm in diameter. The noncystic liver volume was greater than 50%, and the liver had neither fibrosis nor venous congestion. The donor surgery was performed in accordance with the standard protocol without rupture of the cysts. The recipient was a 40-year-old man with cirrhosis associated with hepatitis B. The recipient operation was done by using the piggyback method with no complications. Excessive drainage of chylous ascites (10 000 mL/d) started in the first days after surgery and continued, gradually decreasing until the end of the second month. The patient was discharged with no complications at the end of the third month. No growth in the cysts was observed on follow-up computed tomography scans. Excluding this particular case, a total of 7 other patients have received a polycystic liver transplant. In all 7 cases, the fact that the donor had polycystic liver disease was not known but was encountered by coincidence during procurement. The case reported here is the first case where the polycystic liver disease was diagnosed before procurement and the transplant was still carried out. It appears that, if the donor liver has enough healthy noncystic volume, polycystic livers can be transplanted. PMID:23782669

  13. Women's Health Implications of Polycystic Ovary Syndrome

    NARCIS (Netherlands)

    Veltman-Verhulst, S.M.

    2012-01-01

    Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder of unknown etiology which affects approximately 12% of women. Principal features of PCOS are anovulation resulting in irregular or absent menstruation, excessive androgens (male sex hormones) and ovaries with multiple follicles (polycy

  14. Recessive mutations in the CYP4V2 gene in East Asian and Middle Eastern patients with Bietti crystalline corneoretinal dystrophy

    OpenAIRE

    Lin, J; Nishiguchi, K.; Nakamura, M.; Dryja, T; Berson, E; Miyake, Y

    2005-01-01

    Background: Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessively inherited disorder characterised by tiny yellowish glittering retinal crystals, choroidal sclerosis, and crystals in the peripheral cornea, associated with progressive night blindness. CYP4V2, encoding a member of cytochrome p450 (CYP450) protein family, was recently identified as the causative gene.

  15. Are streamflow recession characteristics really characteristic?

    OpenAIRE

    Stoelzle, M.; Stahl, K.; Weiler, M.

    2012-01-01

    Streamflow recession has been investigated by a variety of methods, often involving the fit of a model to empirical recession plots to parameterize a non-linear storage-outflow relationship. Such recession analysis methods (RAMs) are used to estimate hydraulic conductivity, storage capacity, or aquifer thickness and to model streamflow recession curves for regionalization and prediction at the catchment scale. Numerous RAMs have been published, but little is known about how characteristic ...

  16. Present Day Recession Effects on Human Resources

    OpenAIRE

    Bujor Anca Liliana

    2012-01-01

    Specific characteristic for recession situation are: instability, anxiety, unpredictable attitude and behavior accentuation of knowledge, cognitive filters and erroneous interpretation of social, economic or existential realities. In this paper, for knowing this recession from the perspective of human resources, I started from determining some objectives such as: Knowledge of present recession peculiarities, of its area and depth, learning recession effects, its impact upon human resources, i...

  17. Are streamflow recession characteristics really characteristic?

    OpenAIRE

    Stoelzle, M.; Stahl, K.; Weiler, M.

    2013-01-01

    Streamflow recession has been investigated by a variety of methods, often involving the fit of a model to empirical recession plots to parameterize a non-linear storage–outflow relationship based on the dQ/dtQ method. Such recession analysis methods (RAMs) are used to estimate hydraulic conductivity, storage capacity, or aquifer thickness and to model streamflow recession curves for regionalization and prediction at the catchment scale...

  18. Cleft lip with or without cleft palate in Shanghai, China: Evidence for an autosomal major locus

    Energy Technology Data Exchange (ETDEWEB)

    Marazita, M.L. (Virginia Commonwealth Univ., Richmond, VA (United States)); Hu, Dan-Ning; Liu, You-E. (Zhabei Eye Institute, Shanghai (China)); Spence, A. (Univ. of California, Los Angeles, CA (United States)); Melnick, M. (Univ. of Southern California, Los Angeles, CA (United States))

    1992-09-01

    Orientals are at higher risk for cleft lip with our without cleft palate (CL[+-] P) than Caucasians or blacks. The authors collected demographic and family data to study factors contributing to the etiology of CL[+-]P in Shanghai. The birth incidence of nonsyndromic CL[+-]P (SHanghai 1980-87) was 1.11/1,000, with a male/female ratio of 1.42. Almost 2,000 nonsyndromic CL[+-]P probands were ascertained from individuals operated on during the years 1956-83 at surgical hospitals in Shanghai. Detailed family histories and medical examinations were obtained for the probands and all available family members. Genetic analysis of the probands' families were performed under the mixed model with major locus (ML) and multifactorial (MFT) components. The hypothesis of no familial transmission and of MFT alone could be rejected. Of the ML models, the autosomal recessive was significantly most likely and was assumed for testing three complex hypothesis: (1) ML and sporadics; (2) ML and MFT; (3) ML, MFT, and sporadics. None of the complex models were more likely than the ML alone model. In conclusion, the best-fitting, most parsimonious model for CL[+-]P in Shanghai was that of an autosomal recessive major locus. 37 refs., 1 tab.

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

    Science.gov (United States)

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

    2015-01-01

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

  20. Revised Recession of Reshaping Berm Breakwaters

    DEFF Research Database (Denmark)

    Andersen, Thomas Lykke; Moghim, Mohammad Navid; Burcharth, Hans F.

    2014-01-01

    In this paper data has been collected on berm breakwater stability from several laboratories. The total database contains more than 1500 model test data on berm recession. The data has been compared to five existing recession formulae and most of the existing recession formulae provide good...

  1. Are streamflow recession characteristics really characteristic?

    Directory of Open Access Journals (Sweden)

    M. Stoelzle

    2013-02-01

    Full Text Available Streamflow recession has been investigated by a variety of methods, often involving the fit of a model to empirical recession plots to parameterize a non-linear storage–outflow relationship based on the dQ/dtQ method. Such recession analysis methods (RAMs are used to estimate hydraulic conductivity, storage capacity, or aquifer thickness and to model streamflow recession curves for regionalization and prediction at the catchment scale. Numerous RAMs have been published, but little is known about how comparably the resulting recession models distinguish characteristic catchment behavior. In this study we combined three established recession extraction methods with three different parameter-fitting methods to the power-law storage–outflow model to compare the range of recession characteristics that result from the application of these different RAMs. Resulting recession characteristics including recession time and corresponding storage depletion were evaluated for 20 meso-scale catchments in Germany. We found plausible ranges for model parameterization; however, calculated recession characteristics varied over two orders of magnitude. While recession characteristics of the 20 catchments derived with the different methods correlate strongly, particularly for the RAMs that use the same extraction method, not all rank the catchments consistently, and the differences among some of the methods are larger than among the catchments. To elucidate this variability we discuss the ambiguous roles of recession extraction procedures and the parameterization of the storage–outflow model and the limitations of the presented recession plots. The results suggest strong limitations to the comparability of recession characteristics derived with different methods, not only in the model parameters but also in the relative characterization of different catchments. A multiple-methods approach to investigating streamflow recession

  2. Are streamflow recession characteristics really characteristic?

    Directory of Open Access Journals (Sweden)

    M. Stoelzle

    2012-09-01

    Full Text Available Streamflow recession has been investigated by a variety of methods, often involving the fit of a model to empirical recession plots to parameterize a non-linear storage-outflow relationship. Such recession analysis methods (RAMs are used to estimate hydraulic conductivity, storage capacity, or aquifer thickness and to model streamflow recession curves for regionalization and prediction at the catchment scale. Numerous RAMs have been published, but little is known about how characteristic the resulting recession models are to distinguish characteristic catchment behavior. In this study we combined three established recession extraction methods with three different parameter-fitting methods to the power-law storage-outflow model to compare the range of recession characteristics that result from the application of these different RAMs. Resulting recession characteristics including recession time and corresponding storage depletion were evaluated for 20 meso-scale catchments in Germany. We found plausible ranges for model parameterization, however, calculated recession characteristics varied over two orders of magnitude. While recession characteristics of the 20 catchments derived with the different methods correlate strongly, particularly for the RAMs that use the same extraction method and while they rank the catchments relatively consistent, there are still considerable differences among the methods. To elucidate this variability we discuss the ambiguous roles of recession extraction procedures and the parameterization of storage-outflow model and the limitations of the presented recession plots. The results suggest strong limitations to the comparability of recession characteristics derived with different methods, not only in the model parameters but also in the relative characterization of different catchments. A multiple methods approach to investigate streamflow recession characteristics should be considered for applications whenever possible.

  3. Recession, taxes and economic growth.

    OpenAIRE

    Szarowska, Irena

    2010-01-01

    The current economic situation forces the governments to find solution how to promote economic growth. Economic theory suggests that differences in taxation may play a role in explaining differences in economic performance. The paper summarizes common features tax related measures used to tackling the economic recession in the European Union and it also points out the effect of taxes on economic activity presented by empirical studies.

  4. CRISIS, RECESSION, ECONOMICAL OF ROMANIA

    OpenAIRE

    Ileana ANASTASE (BĂDULESCU); Carmen Maria ANDRUȘCA

    2014-01-01

    The article deals with issues related to the crisis, recession, economical of Romania. By this paper I did not present an anti-crisis plan but I have exposed a number of measures that may cause the settlement of this phenomenon as stimulating the economic growth, protecting citizens and creating jobs. In this context, the article provides and highlights the main markets affected by the economic crisis, these debuting with the estate market, auto market, list that continues until field of educ...

  5. Financial Crisis and Economic Recession

    OpenAIRE

    JESÚS HUERTA DE SOTO

    2011-01-01

    The logic of the historical evolution of the wrong institutional design that affects the financial and monetary system of the so called free market economies up to day is somehow easy to understand: bubbles did continue, financial crisis and economic recessions were not avoided, the bail out of banks was regularly demanded, the lender of last resort was created precisely to bail out the banks.

  6. Recession velocities greater than light

    International Nuclear Information System (INIS)

    It is shown that, for the most commonly discussed models of general relativistic cosmology, distant objects whose velocity of recession exceeds the velocity of light can be observed. Since these are not kinematic velocities there is no violation of the light principle of relativity which can be taken to be:- (1) the velocity of light is a universal constant and (2) a beam of light cannot be overtaken by any material object nor by another light beam. (UK)

  7. Is the financial crisis causing a recession?

    OpenAIRE

    Tatom, John

    2008-01-01

    The U.S. entered a recession in December 2007. Coming in train with a foreclosure crisis that began in late 2006 and its associated financial crisis that began in August 2007, there is a tendency for analysts to attribute the recession to the financial crisis. The worst aspects of the financial crisis that attract attention today did not begin until September 2008 well after the recession began. Other factors account for the recession and could portend the imminent end to the current recess...

  8. Autosomal Dominant Transmission of Accessory Navicular

    OpenAIRE

    Dobbs, Matthew B.; Walton, Tim

    2004-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kleta Robert

    2009-07-01

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

  10. The Jeremiah Metzger Lecture. Polycystic kidney disease: old disease in a new context.

    Science.gov (United States)

    Grantham, Jared J.

    2002-01-01

    , because there wasn't much literature on the subject. The clinical manifestations of PKD were described in the 19th century European medical literature and Sir William Osler had published on the topic in this country, but by and large only a few descriptions of small groups of patients were reported through the middle of the 20th century. In 1957, Dalgaard (2) reported in a classic doctoral thesis that the most common type of hereditary PKD is transmitted as an autosomal dominant trait (ADPKD) with complete penetrance. It is a bilateral renal condition, but cysts also occur in the liver (approximately 60%), pancreas (approximately 10%) and various other organs, and it is associated with cerebral aneurysms in approximately 5% of patients. A recessive form that affects infants and children primarily (ARPKD), is much rarer than ADPKD and commonly leads to death in infancy in association with massively enlarged kidneys (Table 2). I was also attracted to the study of PKD because the etiology was not in question: it had to be mutated DNA. Yet that fact proved to be a hindrance in attaining research support. As some of you will recall, not too long ago genetic diseases were viewed by kidney-oriented NIH review panels to be incurable. I was advised that a young scientist's time would be better spent determining how the kidneys excrete salt and water. Fortunately, the era of molecular genetics and biology was upon us, and we quickly learned that uncommon genetic disorders could lead to the discovery of novel molecules in metabolic and structural pathways. And that is just what happened in the PKD field. The autosomal dominant form of PKD led to the discovery of a unique family of highly complex proteins long before they would have been selected from a gene or proteomic micro-array by some desperate graduate student or fellow. The chromosomal location of the major ADPKD genotype, PKD1, was defined in 1985 (3), a date that marks the beginning of a remarkable period of discovery. PMID

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

    Science.gov (United States)

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

  12. Polycystic ovary syndrome: from phenotype to genetype

    OpenAIRE

    Louwers, Yvonne

    2014-01-01

    markdownabstract__Abstract__ oligomenorrhea or amenorrhea, hirsutism or hyperandrogenism and polycystic ovarian morphology. Later in life, adverse metabolic implications, such as obesity, insulin resistance, type 2 diabetes and cardiovascular disease, become more prominent. In this thesis, we aimed to identify genetic factors for PCOS susceptibility using a candidate-gene approach and a hypothesis-free genome-wide approach. Moreover, we have identified several high-risk groups for long-term h...

  13. Polycystic Ovary Syndrome in the Pediatric Population

    OpenAIRE

    Bremer, Andrew A.

    2010-01-01

    Polycystic ovary syndrome (PCOS) is a common disorder characterized by hyperandrogenism and disordered gonadotropin secretion, often associated with insulin resistance. The syndrome, which modulates both hormonal and metabolic processes, is the most common endocrinopathy in reproductive-age women and increases a woman's risk of infertility, endometrial pathology, and cardiometabolic disease. As it is currently defined, PCOS most likely encompasses several distinct diseases with similar clinic...

  14. Treatment options for polycystic ovary syndrome

    OpenAIRE

    Ahmed Badawy; Abubaker Elnashar

    2011-01-01

    Ahmed Badawy1 Abubaker Elnashar21Department of Obstetrics and Gynecology, Mansoura University, Mansoura, Egypt; 2Department of Obstetrics and Gynecology, Benha University, Benha, EgyptAbstract: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. The clinical manifestation of PCOS varies from a mild menstrual disorder to severe disturbance of reproductive and metabolic functions. Management of women with PCOS depends on the symptoms. These could be ovulatory dysfun...

  15. Features of Polycystic Ovary Syndrome in adolescence

    OpenAIRE

    Tsikouras, P.; Spyros, L; Manav, B; Zervoudis, S.; Poiana, C; Nikolaos, T.; Petros, P; Dimitraki, M; Koukouli, C; Galazios, G; von Tempelhoff, GF

    2015-01-01

    Rationale: To elucidate the prepubertal risk factors associated with the development of Polycystic Ovary Syndrome (PCOS) and determine the special clinical manifestations of the syndrome in this transitional time of a woman’s life. Objective: To propose therapeutic targets and regimens, not only to prevent the long-term complications of the syndrome, but also to improve the self-esteem of a young girl who matures into womanhood. Methods and Results: A systematic review of literature was perfo...

  16. The pathogenetic enigma of polycystic ovary syndrome

    OpenAIRE

    S. Speca; Napolitano, C.; Tagliaferri, G.

    2007-01-01

    Polycystic ovary syndrome (PCOS) is a complex disease with heterogeneous clinical and anatomical features that were first described in 1721 by Antonio Vallisneri. There is still a lack of consensus regarding the criteria to be used for diagnosis of PCOS. Transvaginal ultrasonography with Doppler studies of the ovarian and pelvic vasculature plays an important role in its diagnosis, but findings must be interpreted in light of the patient's symptoms and laboratory findings.

  17. Fetal programming of polycystic ovary syndrome

    OpenAIRE

    Gur, Esra Bahar; Karadeniz, Muammer; Turan, Guluzar Arzu

    2015-01-01

    Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects up to 6.8% of reproductive age women. Experimental research and clinical observations suggest that PCOS may originate in the very early stages of development, possibly even during intrauterine life. This suggests that PCOS is either genetically-transmitted or is due to epigenetic alterations that develop in the intrauterine microenvironment. Although familial cases support the role of genetic factors, no specific gen...

  18. Polycystic ovary syndrome: symptomatology, pathophysiology, and epidemiology.

    Science.gov (United States)

    Guzick, D

    1998-12-01

    Women with polycystic ovary syndrome seek health care for 3 major reasons: infertility, menstrual irregularity, and androgen excess. The infertility is associated with anovulation. The menstrual irregularity is typically chronic, beginning with menarche. Although amenorrhea may sometimes occur, the more common presentation is irregular bleeding characteristic of anovulation. Androgen excess may be manifested by varying degrees of hirsutism. Patients may also report acne. The rapid development of virilizing signs, such as deepening of the voice, increased muscle mass, and temporal balding, should prompt a search for a tumor and lead one away from a diagnosis of polycystic ovary syndrome. Typically treatment is directed at alleviating the symptoms: ovulation induction for infertility, oral contraceptives or a progestin for menstrual irregularity, and oral contraceptives or spironolactone for hirsutism. On the basis of recent epidemiologic data suggestive of increased cardiovascular risk among women with polycystic ovary syndrome, such treatment might be complemented by a long-term approach that addresses the underlying pathophysiology of insulin resistance. PMID:9855614

  19. Obesity and hormonal status of patients with polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Radulović Aleksandar

    2003-01-01

    Full Text Available Introduction Polycystic ovary syndrome is commonly associated with hyperandrogenism and anovulation. The aim of this study was to investigate the impact of obesity on hormonal status in patients with polycystic ovary syndrome. Material and methods The study was performed at the Ward of Obstetrics and Gynecology of the General Hospital in Subotica. A retrospective investigation comprised 39 patients with polycystic ovary syndrome . All patients were in the fertile age-range: 18-38 years. Following ultrasonographic examination and anamnestic data, patients underwent hormonal analyses of follicle-stimulating hormone (FSH, luteinizing hormone (LH, testosterone, prolactin and insulin obtained from the pooled serum sample. Results Values of testosterone and insulin in the group of obese patients with polycystic ovary syndrome were significantly higher than in normal weight patients. Patients with normal body weight index had significantly increased levels of LH in regard to those with increased body weight index. Values of FSH, prolactin and LH/FSH ratio were not significantly different in both groups of polycystic ovary syndrome patients. Increased values of insulin were recorded in 43% of obese and 18.2% of normal weight patients. Conclusion Analysis of investigated results confirmed that obese patients with polycystic ovary syndrome and insulin resistance have been a special clinical entity, whereas an open question remains whether obesity is directly connected with polycystic ovary syndrome or it is only an additional factor interfering with metabolic and hormonal status of genetically predisposed and phenotypically indoctrinated women with polycystic ovary syndrome.

  20. Intracranial dissecting and saccular aneurysms in polycystic kidney disease.

    Science.gov (United States)

    Kulla, L; Deymeer, F; Smith, T W; Weiner, M; Mullins, T F

    1982-12-01

    A young man with polycystic kidney disease was seen initially with an brain-stem infarction. Postmortem examination disclosed a dissecting aneurysm of the basilar artery and a saccular aneurysm of the right vertebral artery. Dissecting intracranial aneurysms rarely are associated with saccular aneurysms and, to our knowledge, have not been reported in association with polycystic kidney disease. PMID:7138321

  1. Cardiometabolic abnormalities in the polycystic ovary syndrome : Pharmacotherapeutic insights

    NARCIS (Netherlands)

    Westerveld, H. E.; Hoogendoorn, M.; de Jong, A. W. F.; Goverde, A. J.; Fauser, B. C. J. M.; Dallinga-Thie, G. M.

    2008-01-01

    The polycystic ovary syndrome (PCOS) affects 5-10% of all premenopausal women. It is diagnosed by a combination of oligo-amenorrhea and hyperandrogenism (NIH criteria) or by the presence of two out of three of: oligo-amenorrhea, hyperandrogenism, polycystic ovaries on ultrasound (Rotterdam criteria)

  2. Polycystic Ovary Syndrome : Genetic determinants of the phenotype

    NARCIS (Netherlands)

    O. Valkenburg (Olivier)

    2015-01-01

    markdownabstract__Abstract__ The polycystic ovary syndrome (PCOS) was first described in 1935 by Stein and Leventhal as an association of amenorrhoea, obesity and a typical, polycystically enlarged, appearance of the ovaries at laparatomy1. Taking into account the absence of advanced imaging techni

  3. Adipose expression of adipocytokines in women with polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Fog Svendsen, Pernille; Christiansen, Michael; Hedley, Paula Louise;

    2012-01-01

    To investigate the role of adipocytokines in the pathophysiology of polycystic ovary syndrome (PCOS) by analyzing the messenger RNA (mRNA) expression and plasma levels of adipocytokines.......To investigate the role of adipocytokines in the pathophysiology of polycystic ovary syndrome (PCOS) by analyzing the messenger RNA (mRNA) expression and plasma levels of adipocytokines....

  4. Common recessive limb girdle muscular dystrophies differential diagnosis: why and how?

    Directory of Open Access Journals (Sweden)

    Ana Cotta

    2014-09-01

    Full Text Available Limb girdle muscular dystrophies are heterogeneous autosomal hereditary neuromuscular disorders. They produce dystrophic changes on muscle biopsy and they are associated with mutations in several genes involved in muscular structure and function. Detailed clinical, laboratorial, imaging, diagnostic flowchart, photographs, tables, and illustrated diagrams are presented for the differential diagnosis of common autosomal recessive limb girdle muscular dystrophy subtypes diagnosed nowadays at one reference center in Brazil. Preoperative image studies guide muscle biopsy site selection. Muscle involvement image pattern differs depending on the limb girdle muscular dystrophy subtype. Muscle involvement is conspicuous at the posterior thigh in calpainopathy and fukutin-related proteinopathy; anterior thigh in sarcoglycanopathy; whole thigh in dysferlinopathy, and telethoninopathy. The precise differential diagnosis of limb girdle muscular dystrophies is important for genetic counseling, prognostic orientation, cardiac and respiratory management. Besides that, it may probably, in the future, provide specific genetic therapies for each subtype.

  5. The trauma of a recession.

    Science.gov (United States)

    Murphy, S M; Kieran, I; Shaughnessy, M O

    2011-09-01

    Employment in construction in Ireland fell by 10% from nearly 282,000 in the second quarter of 2007 to 255,000 in the same period of 2008. Our study looks at the differences in soft tissue upper limb trauma dynamics of a pre- and post-recession Ireland. Construction accounted for 330 patients (27%) of all hand injuries in 2006, but only 18 (3%) in 2009. Our data shows a significant drop in hand injuries related to the construction industry, and more home/DIY cases and deliberate self-harm presenting in their stead. PMID:21431394

  6. CRISIS, RECESSION, ECONOMICAL OF ROMANIA

    Directory of Open Access Journals (Sweden)

    Ileana (BĂDULESCU ANASTASE

    2014-06-01

    Full Text Available The article deals with issues related to the crisis, recession, economical of Romania. By this paper I did not present an anti-crisis plan but I have exposed a number of measures that may cause the settlement of this phenomenon as stimulating the economic growth, protecting citizens and creating jobs. In this context, the article provides and highlights the main markets affected by the economic crisis, these debuting with the estate market, auto market, list that continues until field of education. I have also highlighted the main causes of it, and not least I presented the impact of the crisis upon the most counties in Romania.

  7. The trauma of a recession.

    LENUS (Irish Health Repository)

    Murphy, S M

    2011-09-01

    Employment in construction in Ireland fell by 10% from nearly 282,000 in the second quarter of 2007 to 255,000 in the same period of 2008. Our study looks at the differences in soft tissue upper limb trauma dynamics of a pre- and post-recession Ireland. Construction accounted for 330 patients (27%) of all hand injuries in 2006, but only 18 (3%) in 2009. Our data shows a significant drop in hand injuries related to the construction industry, and more home\\/DIY cases and deliberate self-harm presenting in their stead.

  8. Autosomal dominant rolandic epilepsy with speech dyspraxia.

    Science.gov (United States)

    Scheffer, I E

    2000-01-01

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

  9. Clinical and Molecular Investigations Into Ciliopathies

    Science.gov (United States)

    2016-08-31

    Autosomal Recessive Polycystic Kidney Disease; Congenital Hepatic Fibrosis; Caroli's Disease; Polycystic Kidney Disease; Joubert Syndrome; Cerebro-Oculo-Renal Syndromes; COACH Syndrome; Senior-Loken Syndrome; Dekaban-Arima Syndrome; Cogan Oculomotor Apraxia; Nephronophthisis; Bardet-Biedl Syndrome; Alstrom Syndrome; Oral-Facial-Digital Syndrome

  10. Cleidocranial Dysplasia with Autosomal Dominant Inheritance Pattern

    OpenAIRE

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

    2014-01-01

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

  11. Associations between STR autosomal markers and longevity.

    Science.gov (United States)

    Bediaga, N G; Aznar, J M; Elcoroaristizabal, X; Albóniga, O; Gómez-Busto, F; Artaza Artabe, I; Rocandio, Ana; de Pancorbo, M M

    2015-10-01

    Life span is a complex and multifactorial trait, which is shaped by genetic, epigenetic, environmental, and stochastic factors. The possibility that highly hypervariable short tandem repeats (STRs) associated with longevity has been largely explored by comparing the genotypic pools of long lived and younger individuals, but results so far have been contradictory. In view of these contradictory findings, the present study aims to investigate whether HUMTHO1 and HUMCSF1PO STRs, previously associated with longevity, exert a role as a modulator of life expectancy, as well as to assess the extent to which other autosomal STR markers are associated with human longevity in population from northern Spain. To that end, 21 autosomal microsatellite markers have been studied in 304 nonagenarian individuals (more than 90 years old) and 516 younger controls of European descent. Our results do not confirm the association found in previous studies between longevity and THO1 and CSF1PO loci. However, significant association between longevity and autosomal STR markers D12S391, D22S1045, and DS441 was observed. Even more, when we compared allelic frequency distribution of the 21 STR markers between cases and controls, we found that 6 out of the 21 STRs studied showed different allelic frequencies, thus suggesting that the genomic portrait of the human longevity is far complex and probably shaped by a high number of genomic loci. PMID:26335621

  12. A recessive mutation in the APP gene with dominant-negative effect on amyloidogenesis.

    Science.gov (United States)

    Di Fede, Giuseppe; Catania, Marcella; Morbin, Michela; Rossi, Giacomina; Suardi, Silvia; Mazzoleni, Giulia; Merlin, Marco; Giovagnoli, Anna Rita; Prioni, Sara; Erbetta, Alessandra; Falcone, Chiara; Gobbi, Marco; Colombo, Laura; Bastone, Antonio; Beeg, Marten; Manzoni, Claudia; Francescucci, Bruna; Spagnoli, Alberto; Cantù, Laura; Del Favero, Elena; Levy, Efrat; Salmona, Mario; Tagliavini, Fabrizio

    2009-03-13

    beta-Amyloid precursor protein (APP) mutations cause familial Alzheimer's disease with nearly complete penetrance. We found an APP mutation [alanine-673-->valine-673 (A673V)] that causes disease only in the homozygous state, whereas heterozygous carriers were unaffected, consistent with a recessive Mendelian trait of inheritance. The A673V mutation affected APP processing, resulting in enhanced beta-amyloid (Abeta) production and formation of amyloid fibrils in vitro. Co-incubation of mutated and wild-type peptides conferred instability on Abeta aggregates and inhibited amyloidogenesis and neurotoxicity. The highly amyloidogenic effect of the A673V mutation in the homozygous state and its anti-amyloidogenic effect in the heterozygous state account for the autosomal recessive pattern of inheritance and have implications for genetic screening and the potential treatment of Alzheimer's disease. PMID:19286555

  13. Strategic Management of Entrepreneurial Firms during Recession

    OpenAIRE

    Peltonen, Juhana

    2014-01-01

    The existing research on strategic management and entrepreneurship provides relatively few prescriptions to entrepreneurial firms for navigating recessions. The key managerial problem in recession involves ensuring short-term survival while investing in future growth. However, decision-making during recessions occurs in a context of high uncertainty, which may hinder the ability of managers to take optimal strategic actions.In this doctoral dissertation, I examine these issues mainly through ...

  14. The Superlative Recession and economic policies

    OpenAIRE

    Tatom, John

    2009-01-01

    In late 2008 and early 2009, there has been a serious deterioration in the economic outlook of political leaders, the media and many economic analysts. Comparisons of recent performance and the outlook have degenerated into comparisons with the Great Depression of the 1930s, suggesting that the current recession is the worst since the 1930s. This recession should be called the superlative recession because discussions invariably refer to the most dismal performance since the Great Depression....

  15. Recessed light fixture test facility

    Energy Technology Data Exchange (ETDEWEB)

    Yarbrough, D.W.; Yoo, K.T.; Koneru, P.B.

    1979-07-01

    Test results are presented for the operation of recessed light fixtures in contact with loose fill cellulose insulation. Nine recessed fixtures were operated at different power levels in attic sections in which loose fill cellulose was purposely misapplied. Cellulose insulation was introduced into the ceiling section by pouring to depths of up to nine inches. Maximum steady state temperatures were recorded for 485 combinations of the variables insulation depth, fixture power, and attic temperature. Results are included for operation of fixtures in the absence of cellulose and with barriers to provide needed clearance between the cellulose insulation and the powered fixtures. Observed temperatures on the electrical power cable attached to a fixture and ceiling joists adjacent to powered fixtures are reported. Examination of the data shows excess operating temperatures are encountered when powered fixtures are covered by three inches of loose fill insulation. Dangerous temperatures resulting in fires in some cases were recorded when covered fixtures were operated at above rated power levels. A preliminary analysis indicates that ceiling side heat transfer accounts for 85 to 90% of the heat dissipation from powered fixtures covered by three inches of loose fill cellulosic insulation.

  16. Does Gingival Recession Require Surgical Treatment?

    Science.gov (United States)

    Chan, Hsun-Liang; Chun, Yong-Hee Patricia; MacEachern, Mark; Oates, Thomas W

    2015-10-01

    Gingival recession represents a clinical condition in adults frequently encountered in the general dental practice. Clinicians often face dilemmas of whether or not to treat such a condition surgically. An initial condensed literature search was performed using a combination of gingival recession and surgery controlled terms and keywords. An analysis of the search results highlights the limited understanding of the factors that guide the treatment of gingival recession. Understanding the cause, prognosis, and treatment of gingival recession continues to offer many unanswered questions and challenges in periodontics as we strive to provide the best care possible for our patients. PMID:26427577

  17. Capital Market Development, Frequency of Recession, and Fraction of Time the Economy in Recession

    OpenAIRE

    Tharavanij, Piyapas

    2007-01-01

    This paper investigates the effect of capital market development on the frequency of recession and the fraction of time the economy in recession using quarterly data of thirty-five countries from 1975 to 2004. The main finding is that frequency of recession is not robustly linked to measures of capital market development. However, the fraction of time the economy spends in recession is significantly related to capital market development. This implies that countries with more advanced capital ...

  18. Capital Market, Frequency of Recession, and Fraction of Time the Economy in Recession

    OpenAIRE

    Tharavanij, Piyapas

    2007-01-01

    This paper investigates the relationships of capital markets, frequency of recession, and fraction of time the economy is in recession. The main finding is that frequency of recession is not robustly linked to measures of capital market development. However, the fraction of time the economy spends in recession is significantly related to capital market development, though the marginal effect is small. This implies that countries with more advanced capital markets would tend to spend lower pro...

  19. The Role of G-Protein-Coupled Receptor Proteolysis Site Cleavage of Polycystin-1 in Renal Physiology and Polycystic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Marie Trudel

    2016-01-01

    Full Text Available Polycystin-1 (PC1 plays an essential role in renal tubular morphogenesis, and PC1 dysfunction causes human autosomal dominant polycystic kidney disease. A fundamental characteristic of PC1 is post-translational modification via cleavage at the juxtamembrane GPCR proteolysis site (GPS motif that is part of the larger GAIN domain. Given the considerable biochemical complexity of PC1 molecules generated in vivo by this process, GPS cleavage has several profound implications on the intracellular trafficking and localization in association with their particular function. The critical nature of GPS cleavage is further emphasized by the increasing numbers of PKD1 mutations that significantly affect this cleavage process. The GAIN domain with the GPS motif therefore represents the key structural element with fundamental importance for PC1 and might be polycystic kidney disease’s (PKD Achilles’ heel in a large spectrum of PKD1 missense mutations. We highlight the central roles of PC1 cleavage for the regulation of its biogenesis, intracellular trafficking and function, as well as its significance in polycystic kidney disease.

  20. A mouse model for polycystic kidney disease through a somatic in-frame deletion in the 5' end of Pkd1.

    Science.gov (United States)

    Starremans, P G; Li, X; Finnerty, P E; Guo, L; Takakura, A; Neilson, E G; Zhou, J

    2008-06-01

    Autosomal dominant polycystic kidney disease, a leading cause of end-stage renal disease in adults, is characterized by progressive focal cyst formation in the kidney. Embryonic lethality of Pkd1-targeted mice limits the use of these mice. Here we developed a floxed allele of Pkd1 exons 2-6. Global deletion mutants developed polyhydramnios, hydrops fetalis, polycystic kidney and pancreatic disease. Somatic Pkd1 inactivation in the kidney was achieved by crossing Pkd1(flox) mice with transgenic mice expressing Cre controlled by a gamma-glutamyltranspeptidase promoter. These mutants developed cysts in both proximal and distal nephron segments and survived for about 4 weeks. Somatic loss of heterozygosity was shown in a reporter mouse strain to cause cystogenesis. Some cysts in young mice are positive for multiple tubular markers and a mesenchymal marker, suggesting a delay in tubular epithelial differentiation. A higher cell proliferation rate was observed in distal nephron segments probably accounting for the faster growth rate of distal cysts. Although we observed an overall increase in apoptosis in cystic kidneys, there was no difference between proximal or distal nephron segments. We also found increased cyclic AMP, aquaporin 2 and vasopressin type 2 receptor mRNA levels, and apical membrane translocation of aquaporin 2 in cystic kidneys, all of which may contribute to the differential cyst growth rate observed. The accelerated polycystic kidney phenotype of these mice provides an excellent model for studying molecular pathways of cystogenesis and to test therapeutic strategies. PMID:18385665

  1. Winners and losers in the Great Recession

    OpenAIRE

    Martin, Fernando M.

    2013-01-01

    For a significant number of industries - representing roughly a quarter of the U.S. economy - the most recent recession has been business as usual when judged by pre-recession trends. For a slightly larger group of industries, mostly related to construction, manufacturing, and trade, the contractions have been severe, reinforcing a preexisting process of steady relative decline.

  2. Bond return predictability in expansions and recessions

    DEFF Research Database (Denmark)

    Engsted, Tom; Møller, Stig Vinther; Jensen, Magnus David Sander

    but negative in recessions. The results are also consistent with tests showing that the expectations hypothesis of the term structure holds in recessions but not in expansions. However, the results for bonds are in sharp contrast to results for stocks showing that stock returns are predictable in...

  3. The Effect of Recessions on Firms’ Boundaries

    DEFF Research Database (Denmark)

    Knudsen, Eirik Sjåholm; Foss, Kirsten

    2014-01-01

    The economic theory of the firm offers conflicting predictions of how the two major effects of recessions, changes in demand and access to credit, affect firm boundaries. Using data on Norwegian firms in the recent recession, we find support for both increased and reduced vertical integration of...

  4. Drug discovery for polycystic kidney disease

    Institute of Scientific and Technical Information of China (English)

    Ying SUN; Hong ZHOU; Bao-xue YANG

    2011-01-01

    In polycystic kidney disease (PKD), a most common human genetic diseases, fluid-filled cysts displace normal renal tubules and cause end-stage renal failure. PKD is a serious and costly disorder. There is no available therapy that prevents or slows down the cystogenesis and cyst expansion in PKD. Numerous efforts have been made to find drug targets and the candidate drugs to treat PKD. Recent studies have defined the mechanisms underlying PKD and new therapies directed toward them. In this review article, we summarize the pathogenesis of PKD, possible drug targets, available PKD models for screening and evaluating new drugs as well as candidate drugs that are being developed.

  5. Dangerous triplet: Polycystic ovary syndrome, oral contraceptives and Kounis syndrome

    Institute of Scientific and Technical Information of China (English)

    Nurdan; Erol; Aysu; Turkmen; Karaagac; Nicholas; G; Kounis

    2014-01-01

    Polycystic ovary syndrome is characterized by ovulatory dysfunction, androgen excess and polycystic ovaries and is associated with hypertension, diabetes, metabolic syndrome and cardiovascular events. Oral contraceptives constitute first-line treatment, particularly when symptomatic hyperandrogenism is present. However, these drugs are associated with cardiovascular events and hypersensitivity reactions that pose problem in differential diagnosis and therapy. We present a 14 year-old female with polycystic ovary syndrome taking oral contraceptive and suffering from recurrent coronary ischemic attacks with increased eosinophils, and troponin levels suggesting Kounis syndrome.

  6. NEHRU'S ANTI RECESSION VACCINE HAS IMMUNED INDIA AGAINST GLOBAL RECESSION

    Directory of Open Access Journals (Sweden)

    S.R. KESHAVA

    2013-02-01

    Full Text Available The US economy accounts for ¼ of the world's GDP. The dream developmentof USA was busted when the world major financial giants like Lehman Brothers, BearSterns, AIG, Merill Lynch etc. saw the unprecedented collapse of financial giants. Thelarge Banks in US according to economists and financial experts are like dead manwalking A. sober assessment of the growing mountain of losses from bad debts, measuredin today's market place would over whelm the value of the banks…and they are insolvent(Stere lohr 2009.The LPG reforms were introduced opening the doors on Indian economy. Theeconomic polices pursued by India during the past 40 years prior to July ,1991, oftendubbed as “license –control raj” was described as “mistaken polices” by Dr. ManMohan Singh who was the finance minister in the PV Narismha Rao government andinstrumental in the introduction of reforms. Some individuals even went to the extent ofhailing it as our second independence had arrived. They were happy as they thoughtLPG reforms would free India from a rapacious and domineering state. Theseindividuals were under the intoxication of opium of globalization. They had forgotten theeconomic history. But history repeats itself. India by the end of 2008 saw herself in frontof the world recession. All that state would do was either wrong nor all that market wouldwas right. The LPG not only gives you goodies but also the economic tsunami which eventhe developed world is unable to confront successfully.Nehru was right when he once said 'most of us seldom take the trouble to think.It is a troublesome and fatiguing process and often leads to uncomfortable conclusions.But crises and deadlocks when they occur have at least this advantage that they force usto think' (The Unity of India: Collected Writings, 1937-1940 (1942, p. 94 The majorimpact of recession on India will be on IT& BPO, textiles and garments, automobiles,gems and jewelry, transportation, construction and mining, Hotel

  7. Polycystic ovary syndrome and prolactinoma association.

    Science.gov (United States)

    Yavasoglu, Irfan; Kucuk, Mert; Coskun, Adil; Guney, Engin; Kadikoylu, Gurhan; Bolaman, Zahit

    2009-01-01

    Hyperprolactinemia is the most common pituitary hormone hypersecretion syndrome in both men and women. Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting 5%-10% of reproductive age women. Here, we present a patient with irregular menses, obesity, hirsutism and infertility, and hyperprolactinemia who was diagnosed as PCOS and prolactinoma and admitted to our clinic. Prolactinoma and PCOS association is a rare condition. This 33-year-old woman was admitted to the internal medicine outpatient clinic for irregular menses, obesity, hirsutism and infertility, and hyperprolactinemia. Her laboratory results were as follows: prolactin was 74 ng/mL (normal range:1.8-20.3 ng/mL). Pelvic ultrasonography was correlated with polycystic ovary syndrome. Pituitary MRI showed 6x8 mm microadenoma at left half. Bromocriptine was started with 1.25 mg/day and increased to 5 mg/day. After six months of bromocriptine treatment her prolactin level was normal and no adenoma was detected in pituitary MRI. PCOS and prolactinoma association should be taken into account in PCOS cases with mild hyperprolactinoma. PMID:19367058

  8. Features of Polycystic Ovary Syndrome in adolescence

    Science.gov (United States)

    Tsikouras, P; Spyros, L; Manav, B; Zervoudis, S; Poiana, C; Nikolaos, T; Petros, P; Dimitraki, M; Koukouli, C; Galazios, G; von Tempelhoff, GF

    2015-01-01

    Rationale: To elucidate the prepubertal risk factors associated with the development of Polycystic Ovary Syndrome (PCOS) and determine the special clinical manifestations of the syndrome in this transitional time of a woman’s life. Objective: To propose therapeutic targets and regimens, not only to prevent the long-term complications of the syndrome, but also to improve the self-esteem of a young girl who matures into womanhood. Methods and Results: A systematic review of literature was performed through electronic database searches (Pubmed, Medline and Embase). Studies published in English-language, peer-reviewed journals from 1996 to 2013 were included. The selected studies focused on the risk factors, the unique features and treatment options of the PCOS in puberty. The pathogenesis of the PCOS was hypothesized to be based on interactions between genetic and certain environmental factors. The diagnosis was usually difficult in young girls. The syndrome was related to a greater risk of future infertility, type II diabetes mellitus, the metabolic syndrome and cardiovascular disease. Early treatment was crucial to prevent the long-term complications of the syndrome, especially infertility and cardiovascular disease. Discussion:The recognition of the early signs of PCOS during or even before adolescence is of great importance. It is essential to establish the correct diagnosis for PCOS and rule out other causes of androgen excess in young women with hyperandrogenism. The type of treatment applied should be considered on an individual basis. Abbreviations: PCOS = Polycystic Ovary Syndrome PMID:26351529

  9. Prenatal ultrasonographic findings of renal cystic diseases of the fetus

    International Nuclear Information System (INIS)

    The renal cystic diseases of the fetus consist of variable types of multicystic dysplastic kidney, autosomal recessive polycystic kidney, autosomal dominant polycystic kidney, obstructive cystic renal dysplasia, simple renal cyst, medullary cystic disease, and various syndromes with associated cystic renal diseases. Prenatal US findings of renal cystic diseases were compared and analyzed with the pathologic and postnatal US findings to establish the differential points of renal cystic diseases.

  10. Prenatal ultrasonographic findings of renal cystic diseases of the fetus

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jeong Yeon; Song, Mi Jin; Lee, Young Ho; Cho, Byung Jae; Hong, Sung Ran [Samsung Cheil Hospital, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2002-03-15

    The renal cystic diseases of the fetus consist of variable types of multicystic dysplastic kidney, autosomal recessive polycystic kidney, autosomal dominant polycystic kidney, obstructive cystic renal dysplasia, simple renal cyst, medullary cystic disease, and various syndromes with associated cystic renal diseases. Prenatal US findings of renal cystic diseases were compared and analyzed with the pathologic and postnatal US findings to establish the differential points of renal cystic diseases.

  11. Cystic diseases of the biliary tract and liver

    OpenAIRE

    Nafiye Urgancı

    2008-01-01

    Cystic diseases of liver are recognized in infancy and childhood initially. Cystic diseases of liver and biliary tract are choledocal cysts, autosomal recessive and autosomal dominant polycystic kidney disease, congenital hepatic fibrosis and Caroli disease (cystic dilatation of intrahepatic bile ducts). Choledochal cysts and Caroli disease do not allow biliary flow, cause chronic or obstructive cholestasis and progressive liver disease. In congenital hepatic fibrosis and polycystic kidney di...

  12. When the Turkish word exists Other

    OpenAIRE

    Varken, Türkçesi

    2008-01-01

    Cystic diseases of liver are recognized in infancy and childhood initially Cystic diseases of liver and biliary tract are choledocal cysts autosomal recessive and autosomal dominant polycystic kidney disease congenital hepatic fibrosis and Caroli disease cystic dilatation of intrahepatic bile ducts Choledochal cysts and Caroli disease do not allow biliary flow cause chronic or obstructive cholestasis and progressive liver disease In congenital hepatic fibrosis and polycystic kidney disease th...

  13. Cystic diseases of the biliary tract and liver Invited Editor

    OpenAIRE

    Urgancı, Nafiye

    2008-01-01

    Cystic diseases of liver are recognized in infancy and childhood initially Cystic diseases of liver and biliary tract are choledocal cysts autosomal recessive and autosomal dominant polycystic kidney disease congenital hepatic fibrosis and Caroli disease cystic dilatation of intrahepatic bile ducts Choledochal cysts and Caroli disease do not allow biliary flow cause chronic or obstructive cholestasis and progressive liver disease In congenital hepatic fibrosis and polycystic kidney disease th...

  14. Editorial

    OpenAIRE

    Apak, Hilmi

    2008-01-01

    Cystic diseases of liver are recognized in infancy and childhood initially Cystic diseases of liver and biliary tract are choledocal cysts autosomal recessive and autosomal dominant polycystic kidney disease congenital hepatic fibrosis and Caroli disease cystic dilatation of intrahepatic bile ducts Choledochal cysts and Caroli disease do not allow biliary flow cause chronic or obstructive cholestasis and progressive liver disease In congenital hepatic fibrosis and polycystic kidney disease th...

  15. 12 month old girl with womiting Case of the Month

    OpenAIRE

    Öztürk, Erkut; Önal, Zerrin; Aldemir, Hüseyin; Sander, Serdar

    2008-01-01

    Cystic diseases of liver are recognized in infancy and childhood initially Cystic diseases of liver and biliary tract are choledocal cysts autosomal recessive and autosomal dominant polycystic kidney disease congenital hepatic fibrosis and Caroli disease cystic dilatation of intrahepatic bile ducts Choledochal cysts and Caroli disease do not allow biliary flow cause chronic or obstructive cholestasis and progressive liver disease In congenital hepatic fibrosis and polycystic kidney disease th...

  16. Polycystic ovary syndrome in a virilised, premenarcheal girl.

    OpenAIRE

    Clarke, C F; Piesowicz, A. T.; Edmonds, K.; Grant, D

    1989-01-01

    A premenarcheal girl aged 12 years presented with an abdominopelvic mass and virilisation. A large ovarian cyst was removed at laparotomy. A histological diagnosis of polycystic ovarian syndrome was made, with no evidence of an associated masculinising tumour.

  17. Treatments to Relieve Symptoms of Polycystic Ovary Syndrome (PCOS)

    Science.gov (United States)

    ... L. A., Cedars, M. I., et al. (2011). Physical activity in women with polycystic ovary syndrome: Prevalence, predictors, and positive health associations. American Journal of Obstetrics and Gynecology , 204, 352.e1–352. ...

  18. Insulin and hyperandrogenism in women with polycystic ovary syndrome

    OpenAIRE

    Baptiste, Catherine G.; Battista, Marie-Claude; Trottier, Andréanne; Baillargeon, Jean-Patrice

    2009-01-01

    Polycystic ovary syndrome (PCOS) is a very common endocrine disorder characterized by chronic anovulation, clinical and/or biochemical hyperandrogenism, and/or polycystic ovaries. But most experts consider that hyperandrogenism is the main characteristic of PCOS. Several theories propose different mechanisms to explain PCOS manifestations: (1) a primary enzymatic default in the ovarian and/or adrenal steroidogenesis; (2) an impairment in gonadotropin releasing hormone (GnRH) secretion that pr...

  19. Dangerous triplet: Polycystic ovary syndrome, oral contraceptives and Kounis syndrome

    OpenAIRE

    Erol, Nurdan; Karaagac, Aysu Turkmen; Nicholas G Kounis

    2014-01-01

    Polycystic ovary syndrome is characterized by ovulatory dysfunction, androgen excess and polycystic ovaries and is associated with hypertension, diabetes, metabolic syndrome and cardiovascular events. Oral contraceptives constitute first-line treatment, particularly when symptomatic hyperandrogenism is present. However, these drugs are associated with cardiovascular events and hypersensitivity reactions that pose problem in differential diagnosis and therapy. We present a 14 year-old female wi...

  20. Epidemiology, diagnosis, and management of polycystic ovary syndrome

    OpenAIRE

    Sirmans SM; Pate KA

    2013-01-01

    Susan M Sirmans, Kristen A PateDepartment of Clinical and Administrative Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA, USAAbstract: Polycystic ovary syndrome (PCOS) is a common heterogeneous endocrine disorder characterized by irregular menses, hyperandrogenism, and polycystic ovaries. The prevalence of PCOS varies depending on which criteria are used to make the diagnosis, but is as high as 15%–20% when the European Society for Human Reproduction and...

  1. In vitro function of cyst epithelium from human polycystic kidney.

    OpenAIRE

    Perrone, R D

    1985-01-01

    It is thought that cysts in polycystic kidneys originate from nephron segments and function in a manner similar to the segment or origin. The indirect evidence for this derives from studies of microanatomy and cyst fluid composition. Cysts with low Na+ have been classified as distal, whereas cysts with high Na+ have been classified as proximal. In order to directly determine the transport characteristics of cyst epithelium, cysts from a human polycystic kidney were studied in vitro using Ussi...

  2. Obesity Differentially Affects Phenotypes of Polycystic Ovary Syndrome

    OpenAIRE

    Carlos Moran; Monica Arriaga; Gustavo Rodriguez; Segundo Moran

    2012-01-01

    Obesity or overweight affect most of patients with polycystic ovary syndrome (PCOS). Phenotypes are the clinical characteristics produced by the interaction of heredity and environment in a disease or syndrome. Phenotypes of PCOS have been described on the presence of clinical hyperandrogenism, oligoovulation and polycystic ovaries. The insulin resistance is present in the majority of patients with obesity and/or PCOS and it is more frequent and of greater magnitude in obese than in non obese...

  3. Urine and Plasma Osmolality in Patients with Autosomal Dominant Polycystic Kidney Disease : Reliable Indicators of Vasopressin Activity and Disease Prognosis?

    NARCIS (Netherlands)

    Casteleijn, Niek F.; Zittema, Debbie; Bakker, Stephan J. L.; Boertien, Wendy E.; Gaillard, Carlo A.; Meijer, Esther; Spithoven, Edwin M.; Struck, Joachim; Gansevoort, Ronald

    2015-01-01

    Background: Vasopressin plays an essential role in osmoregulation, but has deleterious effects in patients with ADPKD. Increased water intake to suppress vasopressin activity has been suggested as a potential renoprotective strategy. This study investigated whether urine and plasma osmolality can be

  4. Flow-associated dilatory capacity of the brachial artery is intact in early autosomal dominant polycystic kidney disease

    DEFF Research Database (Denmark)

    Clausen, Peter; Feldt-Rasmussen, Bo; Iversen, Jens; Lange, Martin; Eidemak, Inge; Strandgaard, Svend

    2006-01-01

    [endothelium-independent nitroglycerin-induced dilatation (NID)] were measured by external ultrasound. Plasma concentrations of the stable end products of nitric oxide nitrate/nitrite (NOx) and of the endothelial markers vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1, E-selectin...... and von Willebrand factor antigen were also measured. RESULTS: No differences in FAD or NID were found between patients and controls (104.6 +/- 4.2 vs. 105.3 +/- 3.9%, mean +/- SD, p = 0.55, and 117.0 +/- 8.4 vs. 117.5 +/- 7.6%, p = 0.75). However, the plasma concentration of VCAM-1 was elevated and...

  5. DOUBLE-DIP RECESSION AND POLICY OPTIONS

    OpenAIRE

    Miroljub Labus

    2012-01-01

    It is reasonable to expect the Serbian economy to decline up to -1% in 2012. A double-dip recession is inevitable. Lessons from the previous recession in 2009 suggest that an expansionary fiscal policy has clear limits, and that any misalignment of economic policies might be highly costly.This time, in addition to a recession and lack of policy coordination, the Serbian economy is exposed to the political risk associated with new elections. All of these risks deserve proper attention. In this...

  6. Frontometaphyseal dysplasia: evidence for autosomal dominant inheritance.

    Science.gov (United States)

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

    1976-12-01

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

  7. MRI of autosomal dominant pure spastic paraplegia

    DEFF Research Database (Denmark)

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

    1997-01-01

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

  8. Cleidocranial dysplasia with autosomal dominant inheritance pattern.

    Science.gov (United States)

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

    2014-07-01

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

  9. On identification problems requiring linked autosomal markers.

    Science.gov (United States)

    Egeland, Thore; Sheehan, Nuala

    2008-06-01

    This paper considers identification problems based on DNA marker data. The topics we discuss are general, but we will exemplify them in a simple context. There is DNA available from two persons. There is uncertainty about the relationship between the two individuals and a number of hypotheses describing the possible relationship is available. The task is to determine the most likely pedigree. This problem is fairly standard. However, there are some problems that cannot be solved using DNA from independently segregating loci. For example, the likelihoods for (i) grandparent-grandchild, (ii) uncle-niece and (iii) half-sibs coincide for such DNA data and so these relations cannot be distinguished on the basis of markers normally used for forensic identification problems: the likelihood ratio comparing any pair of hypotheses will be unity. Sometimes, but not in the examples we consider, other sources of DNA like mtDNA or sex chromosomes can help to distinguish between such equally likely possibilities. Prior information can likewise be of use. For instance, age information can exclude alternative (i) above and also indicate that alternative (iii) is apriori more likely than alternative (ii). More generally, the above problems can be solved using linked autosomal markers. To study the problem in detail and understand how linkage works in this regard, we derive an explicit formula for a pair of linked markers. The formula extends to independent pairs of linked markers. While this approach adds to the understanding of the problem, more markers are required to obtain satisfactory results and then the Lander-Green algorithm is needed. Simulation experiments are presented based on a range of scenarios and we conclude that useful results can be obtained using available freeware (MERLIN and R). The main message of this paper is that linked autosomal markers deserve greater attention in forensic genetics and that the required laboratory and statistical analyses can be performed

  10. The Great Recession and confidence in homeownership

    OpenAIRE

    Anat Bracha; Julian Jamison

    2013-01-01

    Confidence in homeownership shifts for those who personally experienced real estate loss during the Great Recession. Older Americans are confident in the value of homeownership. Younger Americans are less confident.

  11. Children's Physical Activity Behavior during School Recess

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Andersen, Henriette Bondo; Troelsen, Jens;

    2016-01-01

    Schoolyards are recognized as important settings for physical activity interventions during recess. However, varying results have been reported. This pilot study was conducted to gain in-depth knowledge of children's physical activity behavior during recess using a mixed-methods approach combining...... participated in go-along group interviews, and recess behavior was observed using an ethnographical participant observation approach. All data were analyzed separated systematically answering the Five W Questions. Children were categorized into Low, Middle and High physical activity groups and these groups...... were predominantly staying in three different locations during recess: school building, schoolyard and field, respectively. Mostly girls were in the building remaining in there because of a perceived lack of attractive outdoor play facilities. The children in the schoolyard were predominantly girls who...

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

    OpenAIRE

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

    2014-01-01

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

  13. Shadow of trouble : the effect of pre-recession characteristics on the severity of recession impact

    OpenAIRE

    Knudsen, Eirik Sjåholm

    2011-01-01

    The recent financial crisis has heightened the need to understand why some firms are more severely affected by recessions than others and how different firm and industry characteristics affect firms’ vulnerability to such shocks. To study these questions empirically, we complement secondary financial data with primary data from an extensive questionnaire about the effects of the recent recession distributed to 5000 Norwegian CEOs in late 2010. We find that high pre-recession operating profit...

  14. Gingival prosthesis: A treatment modality for recession

    OpenAIRE

    Pallavi Samatha Yalamanchili; Hemchand Surapaneni; Arunima Padmakumar Reshmarani

    2013-01-01

    Gingival recession caused due to periodontal disease disturbs patients because of sensitivity and esthetics. Gingival prosthesis may be fixed or removable and can be made from silicones, acrylics, composite resins or ceramics according to what is best suited for the case. The gingival veneer is esthetically appealing and easy to maintain. This case report describes the use of gingival veneer as a treatment modality for recession.

  15. Job creation policies and the Great Recession

    OpenAIRE

    David Neumark

    2012-01-01

    The adverse labor market effects of the Great Recession have intensified interest in policy efforts to spur job creation. The two most direct job creation policies are subsidies that go to workers and hiring credits that go to employers. Evidence indicates that worker subsidies are generally more effective at creating jobs. However, the unique circumstances of recovery from the Great Recession, especially the weak demand for labor, make hiring credits more effective in the short term.

  16. Academic Performance and the Great Recession

    OpenAIRE

    Adamopoulou, Effrosyni; Tanzi, Giulia M.

    2014-01-01

    In this paper we study how the Great Recession affected university students in terms of performance, with a special focus on the dropout probability. To do so, we use individual-level data on a representative sample of university students in Italy in 2007 and 2011. We measure the severity of the recession in terms of increases in adult and youth unemployment rate and we exploit geographical variation to achieve identification. On the one hand, an increase in adult male unemployment rate deter...

  17. Young people and the Great Recession

    OpenAIRE

    Bell, David N.F.; David G. Blanchflower

    2011-01-01

    This article reviews the effects of the Great Recession on youth labour markets. We argue that young people aged 16-24 have suffered disproportionately during the recession. Using the USA and UK as case studies, we analyse youth unemployment using microdata. We argue that there is convincing evidence that the effects of unemployment when young impose costs on individuals and society well into the future. Though the effects of current policies on youth unemployment are uncertain, there is stil...

  18. The diverse impacts of the great recession

    OpenAIRE

    Makoto Nakajima

    2013-01-01

    The Great Recession had a large negative impact on the U.S. economy. Asset prices, most notably stock and house prices, declined substantially, resulting in a loss in wealth for many American households. In this article, Makoto Nakajima documents how diverse households were affected in a variety of dimensions during the Great Recession, in particular between 2007 and 2009, using newly available data from the 2007-2009 Survey of Consumer Finances. He discusses why it is important to look at th...

  19. A Traffic Jam Theory of Recessions

    OpenAIRE

    Jennifer La'O

    2013-01-01

    I construct a dynamic economy in which agents are interconnected: the output produced by one agent is the consumption good of another. I show that this economy can generate recessions which resemble traffic jams. At the micro level, each individual agent waits for his own income to increase before he increases his spending. However, his spending behavior affects the income of another agent. Thus, the spending behavior of agents during recessions resembles the stop-and-go behavior of vehicles ...

  20. Recession-An issue for organizations

    OpenAIRE

    GEORGESCU Daniel

    2009-01-01

    The reality in all organization is that the directors and board are in the position of highest influence and their primary responsibility is leadership. As such, considering the consequences of a recession such as we currently face is not the time for directors to abdicate their responsibilities – it is time for governance leadership. The directors and the board must think and respond strategically. The article shows a matrix for positioning the general manager in recession that is similarly ...