Identification of a Novel Mutation in the ABCA4 Gene in a Chinese Family with Retinitis Pigmentosa Using Exome Sequencing

Abstract

Retinitis pigmentosa (RP) is a group of hereditary, degenerative retinal disorders characterized by progressive retinal dysfunction, outer retina cell loss, and retinal tissue atrophy. It eventually leads to tunnel vision and legal, or total blindness. Here we aimed to reveal the causal gene and mutation contributing to the development of autosomal recessive RP (arRP) in a consanguineous family. A novel homozygous mutation, c.4845delT (p.K1616Rfs*46), in the ATP-binding cassette subfamily A member 4gene ( ABCA4 ) was identified. It may reduce ABCA4 protein activity, leading to progressive degeneration of both rod and cone photoreceptors. The study extends the arRP genotypic spectrum and confirms a genotype-phenotype relationship. This study may also disclose some new clues for RP genetic causes and pathogenesis, as well as clinical and genetic diagnosis. The research findings may contribute to improvement in clinical care, therapy, genetic screening, and counseling.

Keywords: ABCA4; exome sequencing; inherited retinal degeneration; mutation; retinitis pigmentosa.

Figure 1. The mutation c.4845delT (p.K1616Rfs*46) in the ABCA4 gene in a pedigree with RP

(A) Pedigree of the family with arRP. Double lines indicate consanguineous unions. Square denotes male family member, circle represents female family member, slashed symbol indicates deceased family member, fully shaded symbol shows patient with RP, and open symbol presents RP-free member. (B) The ABCA4 sequence with homozygous c.4845delT (p.K1616Rfs*46) mutation (IV:4). (C) The normal ABCA4 sequence of RP-free member (IV:2).

Figure 2. Fundus photographs of the patient (IV:1) with RP

Fundus photographs of both eyes (A: right eye, B: left eye) present bone spicule-like pigmentation, pale fundus, optic nerve atrophy, retinal vessel attenuation, and retinal pigment epithelial degeneration.