| Ciliopathies with skeletal anomalies and renal insufficiency due to mutations in the IFT-A gene WDR19. | |
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MedLine Citation:
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PMID: 22019273 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A subset of ciliopathies, including Sensenbrenner, Jeune, and short-rib polydactyly syndromes are characterized by skeletal anomalies accompanied by multiorgan defects such as chronic renal failure and retinitis pigmentosa. Through exome sequencing we identified compound heterozygous mutations in WDR19 in a Norwegian family with Sensenbrenner syndrome. In a Dutch family with the clinically overlapping Jeune syndrome, a homozygous missense mutation in the same gene was found. Both families displayed a nephronophthisis-like nephropathy. Independently, we also identified compound heterozygous WDR19 mutations by exome sequencing in a Moroccan family with isolated nephronophthisis. WDR19 encodes IFT144, a member of the intraflagellar transport (IFT) complex A that drives retrograde ciliary transport. We show that IFT144 is absent from the cilia of fibroblasts from one of the Sensenbrenner patients and that ciliary abundance and morphology is perturbed, demonstrating the ciliary pathogenesis. Our results suggest that isolated nephronophthisis, Jeune, and Sensenbrenner syndromes are clinically overlapping disorders that can result from a similar molecular cause. |
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Authors:
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Cecilie Bredrup; Sophie Saunier; Machteld M Oud; Torunn Fiskerstrand; Alexander Hoischen; Damien Brackman; Sabine M Leh; Marit Midtbø; Emilie Filhol; Christine Bole-Feysot; Patrick Nitschké; Christian Gilissen; Olav H Haugen; Jan-Stephan F Sanders; Irene Stolte-Dijkstra; Dorus A Mans; Eric J Steenbergen; Ben C J Hamel; Marie Matignon; Rolph Pfundt; Cécile Jeanpierre; Helge Boman; Eyvind Rødahl; Joris A Veltman; Per M Knappskog; Nine V A M Knoers; Ronald Roepman; Heleen H Arts |
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Publication Detail:
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Type: Case Reports; Journal Article; Research Support, Non-U.S. Gov't Date: 2011-10-20 |
Journal Detail:
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Title: American journal of human genetics Volume: 89 ISSN: 1537-6605 ISO Abbreviation: Am. J. Hum. Genet. Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-14 Completed Date: 2012-02-21 Revised Date: 2012-05-11 |
Medline Journal Info:
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Nlm Unique ID: 0370475 Medline TA: Am J Hum Genet Country: United States |
Other Details:
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Languages: eng Pagination: 634-43 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Ophthalmology, Haukeland University Hospital, N-5021 Bergen, Norway. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Child Cilia* / genetics, pathology Craniofacial Abnormalities / genetics Ectodermal Dysplasia / genetics* Exome / genetics Female Fibroblasts / metabolism Flagella / genetics, pathology Humans Male Molecular Sequence Data Morocco Mutation, Missense* Netherlands Norway Oligonucleotide Array Sequence Analysis Pedigree Polycystic Kidney Diseases / congenital, genetics* Proteins / genetics* Short Rib-Polydactyly Syndrome / genetics* Thoracic Diseases / genetics* Young Adult |
| Chemical | |
Reg. No./Substance:
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0/Proteins; 0/WDR19 protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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