Ciliopathies with Skeletal Anomalies and Renal Insufficiency due to Mutations in the IFT-A Gene WDR19
| Autor: | Heleen H. Arts, Nine V A M Knoers, Machteld M. Oud, Jan-Stephan F. Sanders, Marit Midtbø, Sabine Leh, Marie Matignon, Cécile Jeanpierre, Per M. Knappskog, Dorus A. Mans, Ronald Roepman, Ben C.J. Hamel, Irene Stolte-Dijkstra, Eric J. Steenbergen, Eyvind Rødahl, Cecilie Bredrup, Christian Gilissen, Damien Brackman, Emilie Filhol, Olav H. Haugen, Helge Boman, Rolph Pfundt, Torunn Fiskerstrand, Christine Bole-Feysot, Patrick Nitschké, Joris A. Veltman, Sophie Saunier, Alexander Hoischen |
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| Přispěvatelé: | Groningen Kidney Center (GKC), Groningen Institute for Organ Transplantation (GIOT) |
| Rok vydání: | 2011 |
| Předmět: |
Male
RIB-POLYDACTYLY SYNDROME Genetics and epigenetic pathways of disease [NCMLS 6] PROTEIN Ciliopathies Craniofacial Abnormalities Ectodermal Dysplasia Genetics(clinical) Exome Child Genetics (clinical) Exome sequencing Netherlands Oligonucleotide Array Sequence Analysis BARDET-BIEDL-SYNDROME Genetics 0303 health sciences Polycystic Kidney Diseases Norway Cilium 030305 genetics & heredity Intracellular Signaling Peptides and Proteins CRANIOECTODERMAL DYSPLASIA DEFECTS NEPHRONOPHTHISIS 3. Good health Pedigree Sensenbrenner syndrome Morocco INTRAFLAGELLAR TRANSPORT Flagella Female SENSENBRENNER-SYNDROME Adult Adolescent Molecular Sequence Data Mutation Missense PRIMARY CILIA Biology Short Rib-Polydactyly Syndrome 03 medical and health sciences Young Adult Bardet–Biedl syndrome Thoracic Diseases Nephronophthisis Intraflagellar transport Translational research [ONCOL 3] Report medicine Humans Cilia 030304 developmental biology Proteins ASPHYXIATING THORACIC DYSTROPHY Fibroblasts medicine.disease Cytoskeletal Proteins Genetics and epigenetic pathways of disease Renal disorder [NCMLS 6] Genetics and epigenetic pathways of disease Genomic disorders and inherited multi-system disorders [NCMLS 6] |
| Zdroj: | American Journal of Human Genetics, 89, 5, pp. 634-43 American Journal of Human Genetics, 89, 634-43 The American Journal of Human Genetics; Vol 89 American Journal of Human Genetics, 89(5), 634-643. CELL PRESS |
| ISSN: | 0002-9297 |
| Popis: | Item does not contain fulltext 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. |
| Databáze: | OpenAIRE |
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