Mutation of POC1B in a severe syndromic retinal ciliopathy.
Hum Mutat
; 35(10): 1153-62, 2014 Oct.
Article
in En
| MEDLINE
| ID: mdl-25044745
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Retina
/
Cerebellar Diseases
/
Eye Abnormalities
/
Cell Cycle Proteins
/
Kidney Diseases, Cystic
/
Mutation
Type of study:
Prognostic_studies
Limits:
Animals
/
Child
/
Humans
/
Male
Country/Region as subject:
Asia
Language:
En
Journal:
Hum Mutat
Journal subject:
GENETICA MEDICA
Year:
2014
Document type:
Article
Affiliation country: