Please use this identifier to cite or link to this item:
Title: Mutation ofPOC1Bina severe syndromic retinal ciliopathy
Authors: Beck, Bodo B.
Phillips, Jennifer B.
Bartram, Malte P.
Wegner, Jeremy
Thoenes, Michaela
Pannes, Andrea
Sampson, Josephina
Heller, Raoul
Göbel, Heike
Koerber, Friederike
Neugebauer, Antje
Hedergott, Andrea
Nürnberg, Gudrun
Nürnberg, Peter
Thiele, Holger
Altmüller, Janine
Toliat, Mohammad R.
Staubach, Simon
Boycott, Kym M.
Valente, Enza Maria
Janecke, Andreas R.
Eisenberger, Tobias
Bergmann, Carsten
Tebbe, Lars
Wang, Yang
Wu, Yundong
Fry, Andrew M.
Westerfield, Monte
Wolfrum, Uwe
Bolz, Hanno J.
First Published: 17-Jul-2014
Publisher: Wiley
Citation: Human Mutation, 2014, DOI: 10.1002/humu.22618
Abstract: We describe a consanguineous Iraqi family with Leber congenital amaurosis (LCA),Joubert syndrome (JBTS), and polycystic kidney disease. Targeted NGS for excluding mutations in known LCA and JBTS genes, homozygosity mapping and whole-exome sequencing identified a homozygous missense variant, c.317G>C (p.Arg106Pro), in POC1B,a gene essential for ciliogenesis, basal body and centrosome integrity. Insilico modeling suggested a requirement of p.Arg106for formation of the third WD40 repeat and a protein interaction interface. In human and mouse retina, POC1B localized to the basal body and centriole adjacent to the connecting cilium of photoreceptors and in synapses of the outer plexiform layer. Knockdown of Poc1b in zebrafish caused cystic kidneys and retinal degeneration with shortened and reduced photoreceptor connecting cilia, compatible with the human syndromic ciliopathy. A recent study describes homozygosity for p.Arg106Pro[subscript POC1]B in a family with non-syndromic cone-rod dystrophy. The phenotype associated with homozygous p.Arg106Pro[subscript POC1]B may thus be highly variable, analogous to homozygous p.Leu710Ser inWDR19 causing either isolated retinitis pigmentosa or Jeune syndrome. Our study indicates that POC1B is required for retinal integrity, and we propose POC1B mutations as a probable cause for JBTS with severe polycystic kidney disease.
DOI Link: 10.1002/humu.22618
ISSN: 1059-7794
eISSN: 1098-1004
Embargo on file until: 1-Jan-10000
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2014, Wiley. Deposited with reference to the publisher’s open access archiving policy.
Appears in Collections:Published Articles, Dept. of Biochemistry

Files in This Item:
File Description SizeFormat 
humu22618.pdf1.99 MBAdobe PDFView/Open

Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.