Report of a novel mutation in CRB1 in a lebanese family presenting retinal dystrophy

Purpose: To identify the genetic basis of a recessive inheritance form of retinal dystrophy (RD) in a Lebanese family. Materials and methods: Clinical data were recorded for five patients of the 14 family members. Genetic linkage was carried out using Affymetrix 250-K Nspl SNP array followed by sequencing. Results: The patients showed variable phenotypes ranging from Leber Congenital Amaurosis (LCA) to progressive forms of Retinitis Pigmentosa (RP). A 46.1-Mb chromosomal region at chromosome 1q23.3-32.2 was identified by homozygosity mapping. This region contained the Crumbs homologue-1, CRB1, a gene responsible for recessive retinal dystrophies. CRB1 is required for photoreceptor morphogenesis, and it has been associated with RP and LCA. Sequencing of CRB1 revealed two mutations: a novel deletion in exon 6 (c.1772-1775delGCAT; p.C591Sfs*28) and a missense mutation in exon 7 (c.2234C->-T; p.T745M). Conclusion: We report a novel CRB1 mutation in inherited RD in a Lebanese family, and confirm the considerable phenotype heterogeneity that may exist between individuals sharing the same mutations. © 2014 Informa Healthcare USA, Inc. All rights reserved.