Mutation of POC1B in a Severe Syndromic Retinal Ciliopathy

Publication type:
Journal article
Metadata:
Autoren
  • Bodo B Beck
  • Jennifer B Phillips
  • Melte P Bartram
  • Jeremy Wegner
  • Michaele Thoenes
  • Andrea Pannes
  • Josephina Sampson
  • Raoul Heller
  • Heike Goebel
  • Friederike Koerber
  • Antje Neugebauer
  • Andrea Hedergott
  • Gudrun Nuernberg
  • Peter Nuernberg
  • Holger Thiele
  • Janine Altmueller
  • Mohammad R Toliat
  • Simon Staubach
  • Kym M Boycott
  • Enza Maria Valente
  • Andreas R Janecke
  • Tobias Eisenberger
  • Carsten Bergmann
  • Lars Tebbe
  • Yang Wang
  • Yundong Wu
  • Andrew M Fry
  • Monte Westerfield
  • Uwe Wolfrum
  • Hanno J Bolz
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000343012100001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1002/humu.22618
eISSN
1098-1004
Externe Identifier
  • Clarivate Analytics Document Solution ID: AQ7PS
  • PubMed Identifier: 25044745
ISSN
1059-7794
Ausgabe der Veröffentlichung
10
Zeitschrift
HUMAN MUTATION
Schlüsselwörter
  • POC1B
  • LCA
  • Joubert syndrome
  • cliopathy
  • zebrafish
Paginierung
1153 - 1162
Datum der Veröffentlichung
2014
Status
Published
Titel
Mutation of <i>POC1B</i> in a Severe Syndromic Retinal Ciliopathy
Sub types
  • Article
Ausgabe der Zeitschrift
35

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Bodo B Beck
  • Jennifer B Phillips
  • Malte P Bartram
  • Jeremy Wegner
  • Michaela Thoenes
  • Andrea Pannes
  • Josephina Sampson
  • Raoul Heller
  • Heike Göbel
  • Friederike Koerber
  • Antje Neugebauer
  • Andrea Hedergott
  • Gudrun Nürnberg
  • Peter Nürnberg
  • Holger Thiele
  • Janine Altmüller
  • Mohammad R Toliat
  • Simon Staubach
  • Kym M Boycott
  • Enza Maria Valente
  • Andreas R Janecke
  • Tobias Eisenberger
  • Carsten Bergmann
  • Lars Tebbe
  • Yang Wang
  • Yundong Wu
  • Andrew M Fry
  • Monte Westerfield
  • Uwe Wolfrum
  • Hanno J Bolz
DOI
10.1002/humu.22618
ISSN
1059-7794
Ausgabe der Veröffentlichung
10
Zeitschrift
Human Mutation
Sprache
en
Online publication date
2014
Paginierung
1153 - 1162
Datum der Veröffentlichung
2014
Status
Published
Herausgeber
Hindawi Limited
Herausgeber URL
http://dx.doi.org/10.1002/humu.22618
Datum der Datenerfassung
2022
Titel
Mutation of<i>POC1B</i>in a Severe Syndromic Retinal Ciliopathy
Ausgabe der Zeitschrift
35

Data source: Crossref

Abstract
We describe a consanguineous Iraqi family with Leber congenital amaurosis (LCA), Joubert syndrome (JBTS), and polycystic kidney disease (PKD). Targeted next-generation sequencing 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. In silico modeling suggested a requirement of p.Arg106 for the 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.Arg106ProPOC1B in a family with nonsyndromic cone-rod dystrophy. The phenotype associated with homozygous p.Arg106ProPOC1B may thus be highly variable, analogous to homozygous p.Leu710Ser in WDR19 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 PKD.
Addresses
  • Institute of Human Genetics, University Hospital of Cologne, Cologne, Germany.
Autoren
  • Bodo B Beck
  • Jennifer B Phillips
  • Malte P Bartram
  • Jeremy Wegner
  • Michaela Thoenes
  • Andrea Pannes
  • Josephina Sampson
  • Raoul Heller
  • Heike Göbel
  • Friederike Koerber
  • Antje Neugebauer
  • Andrea Hedergott
  • Gudrun Nürnberg
  • Peter Nürnberg
  • Holger Thiele
  • Janine Altmüller
  • Mohammad R Toliat
  • Simon Staubach
  • Kym M Boycott
  • Enza Maria Valente
  • Andreas R Janecke
  • Tobias Eisenberger
  • Carsten Bergmann
  • Lars Tebbe
  • Yang Wang
  • Yundong Wu
  • Andrew M Fry
  • Monte Westerfield
  • Uwe Wolfrum
  • Hanno J Bolz
DOI
10.1002/humu.22618
eISSN
1098-1004
Externe Identifier
  • PubMed Identifier: 25044745
  • PubMed Central ID: PMC4425427
Funding acknowledgements
  • NICHD NIH HHS: P01 HD022486
  • Kidney Research UK: RP2/2013
  • Marie Louise Geissler-Stiftung:
  • NIDCD NIH HHS: DC004186
  • NIDCD NIH HHS: R01 DC010447
  • NIH HHS: OD011195
  • NIDCD NIH HHS: R01 DC004186
  • NIH HHS: R24 OD011195
  • Worldwide Cancer Research: 13-0042
  • Imhoff-Stiftung:
  • Biotechnology and Biological Sciences Research Council: BB/F010702/1
  • NICHD NIH HHS: HD22486
  • NIDCD NIH HHS: DC010447
Open access
false
ISSN
1059-7794
Ausgabe der Veröffentlichung
10
Zeitschrift
Human mutation
Schlüsselwörter
  • Kidney
  • Cerebellum
  • Retina
  • Cilia
  • Animals
  • Zebrafish
  • Humans
  • Mice
  • Cerebellar Diseases
  • Eye Abnormalities
  • Abnormalities, Multiple
  • Cell Cycle Proteins
  • Pedigree
  • Amino Acid Sequence
  • Amino Acid Motifs
  • Mutation
  • Molecular Sequence Data
  • Child
  • Iraq
  • Male
  • Kidney Diseases, Cystic
  • Gene Knockdown Techniques
  • Leber Congenital Amaurosis
Sprache
eng
Medium
Print-Electronic
Online publication date
2014
Paginierung
1153 - 1162
Datum der Veröffentlichung
2014
Status
Published
Datum der Datenerfassung
2014
Titel
Mutation of POC1B in a severe syndromic retinal ciliopathy.
Sub types
  • Research Support, Non-U.S. Gov't
  • research-article
  • Journal Article
  • Case Reports
  • Research Support, N.I.H., Extramural
Ausgabe der Zeitschrift
35

Files

https://europepmc.org/articles/PMC4425427?pdf=render

Data source: Europe PubMed Central

Abstract
We describe a consanguineous Iraqi family with Leber congenital amaurosis (LCA), Joubert syndrome (JBTS), and polycystic kidney disease (PKD). Targeted next-generation sequencing 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. In silico modeling suggested a requirement of p.Arg106 for the 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.Arg106ProPOC1B in a family with nonsyndromic cone-rod dystrophy. The phenotype associated with homozygous p.Arg106ProPOC1B may thus be highly variable, analogous to homozygous p.Leu710Ser in WDR19 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 PKD.
Date of acceptance
2014
Autoren
  • Bodo B Beck
  • Jennifer B Phillips
  • Malte P Bartram
  • Jeremy Wegner
  • Michaela Thoenes
  • Andrea Pannes
  • Josephina Sampson
  • Raoul Heller
  • Heike Göbel
  • Friederike Koerber
  • Antje Neugebauer
  • Andrea Hedergott
  • Gudrun Nürnberg
  • Peter Nürnberg
  • Holger Thiele
  • Janine Altmüller
  • Mohammad R Toliat
  • Simon Staubach
  • Kym M Boycott
  • Enza Maria Valente
  • Andreas R Janecke
  • Tobias Eisenberger
  • Carsten Bergmann
  • Lars Tebbe
  • Yang Wang
  • Yundong Wu
  • Andrew M Fry
  • Monte Westerfield
  • Uwe Wolfrum
  • Hanno J Bolz
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/25044745
DOI
10.1002/humu.22618
eISSN
1098-1004
Externe Identifier
  • NIH Manuscript Submission ID: NIHMS620742
  • PubMed Central ID: PMC4425427
Funding acknowledgements
  • NIDCD NIH HHS: DC004186
  • Biotechnology and Biological Sciences Research Council: BB/F010702/1
  • NICHD NIH HHS: P01 HD022486
  • NIDCD NIH HHS: R01 DC010447
  • NIH HHS: OD011195
  • NIDCD NIH HHS: R01 DC004186
  • Worldwide Cancer Research: 13-0042
  • NICHD NIH HHS: HD22486
  • NIDCD NIH HHS: DC010447
  • NIH HHS: R24 OD011195
Ausgabe der Veröffentlichung
10
Zeitschrift
Hum Mutat
Schlüsselwörter
  • Joubert syndrome
  • LCA
  • POC1B
  • ciliopathy
  • zebrafish
  • Abnormalities, Multiple
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Cell Cycle Proteins
  • Cerebellar Diseases
  • Cerebellum
  • Child
  • Cilia
  • Eye Abnormalities
  • Gene Knockdown Techniques
  • Humans
  • Iraq
  • Kidney
  • Kidney Diseases, Cystic
  • Leber Congenital Amaurosis
  • Male
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Pedigree
  • Retina
  • Zebrafish
Sprache
eng
Country
United States
Paginierung
1153 - 1162
Datum der Veröffentlichung
2014
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2015
Titel
Mutation of POC1B in a severe syndromic retinal ciliopathy.
Sub types
  • Case Reports
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
35

Data source: PubMed

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