Detection of CRB1 mutations in families with retinal dystrophy through phenotype-oriented mutational screening

Mutations in the crumbs homolog (CRB)1 gene are among the common causes of severe early onset retinal dystrophy. Some characteristic clinical phenotypes are frequently associated with mutations in CRB1. The aim of this study was to examine whether characteristic phenotype-directed mutational screening facilitated the detection of CRB1 mutations. The study included 22 probands with at least one of the potential CRB1-associated phenotypes for retinal dystrophy. Variants were detected using Sanger sequencing. The complete sequences of the coding and adjacent intronic regions of CRB1 were analyzed, revealing homozygous or compound heterozygous mutations in CRB1 in seven of 22 probands, involving six novel (c.136delA, c.1841G>T, c.3017C>A, c.3488G>T, c.3991C>T and c.4089dupTGTTGCTT) and four known (c.2222T>C, c.2671T>G, c.3676G>T and c.4005+2T>G) mutations. The mutations were present in three of four probands with macular nummular pigmentation and in four of seven probands with early onset retinitis pigmentosa with macular involvement. The results suggested that macular nummular pigmentation is a gene-specific indication for CRB1‑associated retinal dystrophy and confirm that CRB1 mutations are also common causes of early onset retinitis pigmentosa. Identification of gene-specific phenotypes is uselful in identifying genetic defects underlying heterogeneous retinal dystrophy.