Expanding CEP290mutational spectrum in ciliopathiesHow to cite this article: Travaglini L, Brancati F, AttieBitach T, Audollent S, Bertini E, Kaplan J, Perrault I, Iannicelli M, Mancuso B, Rigoli L, Rozet J, Swistun D, Tolentino J, The International JSRD Study Group, Dallapiccola B, Gleeson JG, Valente EM. 2009. Expanding CEP290mutational spectrum in ciliopathies. Am J Med Genet Part A 149A:2173–2180.

Ciliopathies are an expanding group of rare conditions characterized by multiorgan involvement, that are caused by mutations in genes encoding for proteins of the primary cilium or its apparatus. Among these genes, CEP290bears an intriguing allelic spectrum, being commonly mutated in Joubert syndrome and related disorders JSRD, Meckel syndrome MKS, SeniorLoken syndrome and isolated Leber congenital amaurosis LCA. Although these conditions are recessively inherited, in a subset of patients only one CEP290mutation could be detected. To assess whether genomic rearrangements involving the CEP290gene could represent a possible mutational mechanism in these cases, exon dosage analysis on genomic DNA was performed in two groups of CEP290heterozygous patients, including five JSRDMKS cases and four LCA, respectively. In one JSRD patient, we identified a large heterozygous deletion encompassing CEP290Cterminus that resulted in marked reduction of mRNA expression. No copy number alterations were identified in the remaining probands. The present work expands the CEP290genotypic spectrum to include multiexon deletions. Although this mechanism does not appear to be frequent, screening for genomic rearrangements should be considered in patients in whom a single CEP290mutated allele was identified. © 2009 WileyLiss, Inc.