2. Academic Validation
  3. Ciliopathies with skeletal anomalies and renal insufficiency due to mutations in the IFT-A gene WDR19

Ciliopathies with skeletal anomalies and renal insufficiency due to mutations in the IFT-A gene WDR19

  • Am J Hum Genet. 2011 Nov 11;89(5):634-43. doi: 10.1016/j.ajhg.2011.10.001.
Cecilie Bredrup 1,  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
Affiliations

Affiliation

  • 1 Department of Ophthalmology, Haukeland University Hospital, N-5021 Bergen, Norway.
PMID: 22019273 DOI: 10.1016/j.ajhg.2011.10.001
Abstract

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.

Figures