Objective To identify the pathogenic mutation in a Chinese family with autosomal recessive retinitis pigmentosa (RP) and to analyze its genotype-phenotype correlations. Methods Seven participants from one family were recruited for this experimental study, including 2 patients and 5 asymptomatic siblings. All participants underwent comprehensive ophthalmic examinations including best-corrected visual acuity, visual field testing, fundus photography, optical coherence tomography, and full-field flash electroretinography. Targeted next-generation sequencing (NGS) was selectively performed on the proband to reveal the RP causative mutation in this family using a microarray targeting 180 reported inherited retinal dystrophies (IRDs) causative genes and 9 potential IRDs relevant genes. All variants initially detected by NGS were then screened and filtered with optimized bioinformatics analyses and validated by intra-familial cosegregation analyses using Sanger sequencing. Genotype-phenotype correlation was also analyzed. Results Ophthalmic examination suggested the clinical diagnosis of typical RP for both patients from this family. Genetic analysis indicated ABCA4 c.419G>A as the RP causative mutation for this family. This mutation induced the amino acid change from arginine to glutamine at residue 140 of the protein encoded by the ABCA4 gene (p.Arg140Gln). Conservational analysis revealed the high conservation of the mutational spot among all tested species, and the online predictive software, PolyPhen-2, suggested the pathogenicity of this mutation. Conclusion By means of a targeted NGS approach, this study identifies a novel mutation, ABCA4 p.Arg140Gln, as the disease causative mutation for a Chinese autosomal recessive RP family, which extends both the genotypic and phenotypic spectrums for the ABCA4 gene.
丁思加,陈雪,赵堪兴,盛迅伦,赵晨. 目标区域捕获测序检测到一视网膜色素变性家系ABCA4基因新突变[J]. 中华眼视光学与视觉科学杂志, 2016, 18(3): 142-147.
Ding Sijia*,Chen Xue,Zhao Kanxing,Sheng Xunlun,Zhao Chen. Targeted next-generation sequencing identifies a novel ABCA4 gene mutation in a Chinese family with retinitis pigmentosa . Chinese Journal of Optometry Ophthalmology and Visual science, 2016, 18(3): 142-147. DOI: 10.3760/cma.j.issn.1674-845X.2016.03.004
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