Identification of a novel missense mutation of RPE۶۵ gene causing Leber congenital amaurosis ۲

Leber congenital amaurosis comprises a group of early-onset childhood retinal dystrophies characterized by vision loss, nystagmus, and severe retinal dysfunction. LCA is genetically heterogeneous. In this study, we investigated the genetic cause of vision loss in three consanguineous blind patients from Semnan. Therefore, Next Generation Illumina Sequencing was performed to enrich all exons of more than ۲۲۰۰۰ genes in the proband. Subsequently, Sanger sequencing was used to confirm the mutation found in his parents and two other blind patients. The obtained results showed a novel homozygous missense mutation NM_۰۰۰۳۲۹:exon۳:c.T۱۷۰C:p.F۵۷S in the RPE۶۵ gene of proband. In addition, his parents and the other two blind patients were heterozygote and mutated homozygous, respectively. On the other hands, in silico analyses using mutation taster, polyphen, SIFT, CADD_phred and REVEL software were confirmed the pathogenicity of a novel missense mutation found in the RPE۶۵ gene. The RPE۶۵ protein encoded by RPE۶۵ gene is involved in a multi-step process called the visual cycle, which converts light entering the eye into electrical signals that are transmitted to the brain. In fact, the RPE۶۵ protein then helps convert all-trans retinal back to ۱۱-cis retinal so the visual cycle can begin again. Mutations in this gene are associated with early-onset severe blinding disorders called Leber congenital amaurosis ۲ (LCA۲) and retinitis pigmentosa ۲۰. Altogether, such studies can be aid to conduct genetic counseling, prenatal diagnosis and clinical management of these types of inherited disorders.

کلیدواژه ها:

Vision loss ، LCA۲ ، RPE۶۵ gene ، Next Generation Sequencing ، Genetic counselling