ALBERT

Description:    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. Content Type Journal Article Category Original Investigation Pages 1-15 DOI 10.1007/s00439-012-1228-5 Authors Magdalena Cardenas-Rodriguez, Human Molecular Genetics Laboratory, Institut Pasteur de Montevideo, Mataojo 2020, 11400 Montevideo, Uruguay Daniel P. S. Osborn, Molecular Medicine Unit, Institute of Child Health, University College London, 30 Guilford St, London, WC1N 1EH UK Florencia Irigoín, Human Molecular Genetics Laboratory, Institut Pasteur de Montevideo, Mataojo 2020, 11400 Montevideo, Uruguay Martín Graña, Bioinformatics Unit, Institut Pasteur de Montevideo, Mataojo 2020, 11400 Montevideo, Uruguay Héctor Romero, Laboratorio de Organización y Evolución del Genoma, Facultad de Ciencias/C.U.R.E., Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay Philip L. Beales, Molecular Medicine Unit, Institute of Child Health, University College London, 30 Guilford St, London, WC1N 1EH UK Jose L. Badano, Human Molecular Genetics Laboratory, Institut Pasteur de Montevideo, Mataojo 2020, 11400 Montevideo, Uruguay Journal Human Genetics Online ISSN 1432-1203 Print ISSN 0340-6717