Rapid identification of pathogenic mutations in sporadic hereditary retinal dystrophies using targeted next-generation sequencing
10.3760/cma.j.issn.2095-0160.2017.12.009
- VernacularTitle:应用目标基因捕获结合二代测序技术检测无遗传性眼病家族史的遗传性视网膜疾病患者的致病基因
- Author:
Xinhe FANG
1
;
Fangxia ZHANG
;
Yan ZHU
;
Yani LIU
;
Xunlun SHENG
Author Information
1. 宁夏回族自治区人民医院宁夏眼科医院西北民族大学第一附属医院
- Keywords:
Hereditary retinal disease;
Pathogenic mutations;
Target gene capture;
Next-generation sequencing
- From:
Chinese Journal of Experimental Ophthalmology
2017;35(12):1097-1103
- CountryChina
- Language:Chinese
-
Abstract:
Background Hereditary retinal diseases (HRDs) are a group of retinal degenerative diseases with significant genetic and clinical heterogeneities.Traditional techniques are challenging for detection of pathogenic mutations.Objective This study was to identify the diseasing-causal genes in 20 Chinese families with a variety of HRDs.Methods Family histories and ophthalmic examinations were obtained from all participants in 20 sporadic families.Targeted sequence capture array technique with next-generation sequencing (NGS) was performed to detect pathogenic mutations in 232 identified genes associated with HRDs.Variants detected by NGS were filtered by bioinformatic analysis HRDs.Genotype-phenotype correlation was also assessed.Results We identified 11 patients with pathogenic mutations,including 8 compound heterozygous mutations and 3 homozygous mutations,which were not yet reported.These findings showed genetic diagnoses in 11 of 20 patients,with the positive rate of 55％.Among them,6 patients were autosomal recessive inheritance and 5 were unspecific.Identification of different mutations and divergent phenotypes revealed 5 patients were affected with cone-rod dystrophy,3 patients with Leber congenital amaurosis,1 patient with congenital stationary night blindness,1 patient with Best vitelliform macular dystrophy and 1 patient with Stargardt disease.Conclusions Targeted NGS is an effective approach for the genetic diagnoses of HRDs.These findings provide insights into understanding the genotype-phenotype correlations in HRDs.
