Characterization of CCDC28B reveals its role in ciliogenesis and provides insight to understand its modifier effect on Bardet-Biedl syndrome.
Hum Genet
; 132(1): 91-105, 2013 Jan.
Article
em En
| MEDLINE
| ID: mdl-23015189
ABSTRACT
Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder that is generally inherited in an autosomal recessive fashion. However, in some families, trans mutant alleles interact with the primary causal locus to modulate the penetrance and/or the expressivity of the phenotype. CCDC28B (MGC1203) was identified as a second site modifier of BBS encoding a protein of unknown function. Here we report the first functional characterization of this protein and show it affects ciliogenesis both in cultured cells and in vivo in zebrafish. Consistent with this biological role, our in silico analysis shows that the presence of CCDC28B homologous sequences is restricted to ciliated metazoa. Depletion of Ccdc28b in zebrafish results in defective ciliogenesis and consequently causes a number of phenotypes that are characteristic of BBS and other ciliopathy mutants including hydrocephalus, left-right axis determination defects and renal function impairment. Thus, this work reports CCDC28B as a novel protein involved in the process of ciliogenesis whilst providing functional insight into the cellular basis of its modifier effect in BBS patients.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peixe-Zebra
/
Cílios
/
Proteínas de Ciclo Celular
/
Síndrome de Bardet-Biedl
/
Proteínas de Peixe-Zebra
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Hum Genet
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Uruguai