Beck, Bodo B., Phillips, Jennifer B., Bartram, Melte P., Wegner, Jeremy, Thoenes, Michaele, Pannes, Andrea, Sampson, Josephina, Heller, Raoul, Goebel, Heike, Koerber, Friederike, Neugebauer, Antje, Hedergott, Andrea, Nuernberg, Gudrun, Nuernberg, Peter, Thiele, Holger, Altmueller, Janine, Toliat, Mohammad R., Staubach, Simon, Boycott, Kym M., Valente, Enza Maria ORCID: 0000-0002-0600-6820, Janecke, Andreas R., Eisenberger, Tobias, Bergmann, Carsten, Tebbe, Lars, Wang, Yang, Wu, Yundong, Fry, Andrew M., Westerfield, Monte, Wolfrum, Uwe and Bolz, Hanno J. (2014). Mutation of POC1B in a Severe Syndromic Retinal Ciliopathy. Hum. Mutat., 35 (10). S. 1153 - 1163. HOBOKEN: WILEY. ISSN 1098-1004

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Abstract

We describe a consanguineous Iraqi family with Leber congenital arnaurosis (LCA), Jouber syndrome (JBTS), and polycystic kidney disease (PI(I)). Targeted next-generation sequencing for excluding mutations in known LCA and JBTS genes, homozygosity mapping, and whole-exome sequencing identified a homozygous misnse variant, c.317G>C (p.Arg106Pro), in POC1B, a gene essential for ciliogenesis, basal body, and centrosome integrity. In silico modeling suggested a requirement of p.Arg106Pro(POCIB) for the formation of the third WI)40 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 Poclb in zebrafish caused cystic kidneys and retinal degeneration with shortened and reduced photor p or connecting cilia, compatible with the human syndromic ciliopathy. A recent study describes hotnozygosfor p.Arg106PrnPociB in a family with nonsyndromic cone-rod dystrophy. The phenotype associated with homozygous p.Arg106Propocth may thus be highly variable, analogous to homozygous p.Lett710Ser in WDR19 causing either isolated retinitis pigmentosa or Jeune syndrome. Our study indicates that POC1B is required for retinal ingrity, and we propose POC1B mutations as a probable cause for JBTS with severe PKD.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Beck, Bodo B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Phillips, Jennifer B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bartram, Melte P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wegner, JeremyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thoenes, MichaeleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pannes, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sampson, JosephinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heller, RaoulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goebel, HeikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koerber, FriederikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neugebauer, AntjeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hedergott, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, GudrunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thiele, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toliat, Mohammad R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Staubach, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boycott, Kym M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Valente, Enza MariaUNSPECIFIEDorcid.org/0000-0002-0600-6820UNSPECIFIED
Janecke, Andreas R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eisenberger, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bergmann, CarstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tebbe, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, YangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wu, YundongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fry, Andrew M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Westerfield, MonteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolfrum, UweUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bolz, Hanno J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-428059
DOI: 10.1002/humu.22618
Journal or Publication Title: Hum. Mutat.
Volume: 35
Number: 10
Page Range: S. 1153 - 1163
Date: 2014
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1098-1004
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
LEBER CONGENITAL AMAUROSIS; SENIOR-LOKEN SYNDROME; JOUBERT-SYNDROME; LINKAGE ANALYSIS; DOMAIN PROTEIN; CILIARY; GENE; DISEASE; CELLS; NEPHRONOPHTHISISMultiple languages
Genetics & HeredityMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/42805

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