Novel compound heterozygous mutation in the CNGA1 gene underlie autosomal recessive retinitis pigmentosa in a Chinese family

Biosci Rep. 2016 Jan 22;36(1):e00289. doi: 10.1042/BSR20150131. Print 2016.

Abstract

Retinitis pigmentosa (RP) describes a group of inherited retinopathies that are characterized by the progressive degeneration of photoreceptor neurons, which causes night blindness, a reduction in the peripheral visual field and decreased visual acuity. More than 50 RP-related genes have been identified. In the present study, we analysed a Chinese family with autosomal recessive RP. We identified a compound heterozygous mutation, c.265delC and c.1537G>A, in CNGA1 using targeted next-generation sequencing (NGS) of RP-causing genes. The mutations were validated in the family members by Sanger sequencing. The mutations co-segregated with the RP phenotype and were absent from ethnically-matched control chromosomes. The mutant (mut) CNGA1 p.(G513R) protein caused by the mis-sense novel mutation c.1537G>A was expressed in vitro. The mut CNGA1 p.(G513R) protein was largely retained inside the cell rather than being targeted to the plasma membrane, suggesting the absence of cGMP-gated cation channels in the plasma membrane would be deleterious to rod photoreceptors, leading lead to RP.

Keywords: CNGA1; mutation; next-generation sequencing; retinitis pigmentosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Asian People
  • Cyclic Nucleotide-Gated Cation Channels / genetics*
  • Family*
  • Female
  • Heterozygote*
  • Humans
  • Male
  • Mutation, Missense*
  • Retinitis Pigmentosa / genetics*

Substances

  • CNGA1 protein, human
  • Cyclic Nucleotide-Gated Cation Channels