Identification of a CNGB1 Frameshift Mutation in a Han Chinese Family with Retinitis Pigmentosa.

SIGNIFICANCE: Retinitis pigmentosa (RP) is a severe hereditary retinal disorder characterized by progressive degeneration of rod and cone photoreceptors. This study identified a novel frameshift mutation, c.385delC, p.(L129WfsTer148), in the cyclic nucleotide-gated channel beta 1 (CNGB1) gene of a consanguineous Han Chinese family with autosomal recessive RP (arRP). This expands the spectrum of CNGB1 gene variants in RP cases and possibly refines future genetic counseling.

PURPOSE: The present study sought to identify potential pathogenetic gene mutations in a five-generation consanguineous Han Chinese family with RP.

METHODS: Two members of a five-generation consanguineous Han Chinese pedigree with arRP and 100 normal individuals were enrolled in this study. Exome sequencing was performed on the 70-year-old male proband from a consanguineous family to screen potential pathogenic mutations according to the American College of Medical Genetics and Genomics for the interpretation of sequence variants. Sanger sequencing was performed on the proband, the proband's unaffected son, and 100 normal individuals to verify the disease-causing mutation.

RESULTS: A novel frameshift mutation, c.385delC, p.(L129WfsTer148), with homozygous status in the CNGB1 gene was identified in the proband of the family with arRP, and the mutation with heterozygous status was carried by the asymptomatic son.

CONCLUSIONS: The c.385delC (p.(L129WfsTer148)) mutation in the CNGB1 gene screened by exome sequencing is probably responsible for the RP phenotype in this family. The result expands the spectrum of CNGB1 gene variants in RP cases and possibly refines future genetic counseling.