Wang Lihua, Qi Anhui, Pan Hong, Liu Beihong, Feng Jingjing, Chen Wei, Wang Binbin
Department of Ophthalmology, Beijing Haidian Maternal and Child Health Hospital Graduate School of Peking Union Medical College Center for Genetics, National Research Institute for Family Planning, Beijing, China.
Medicine (Baltimore). 2018 Aug;97(32):e11499. doi: 10.1097/MD.0000000000011499.
Cone-rod dystrophy (CORD) is an inherited, progressive retinal disorder with genetic and phenotypic heterogeneity. Here, we aimed to identify the pathogenic mutation in affected individuals in a Chinese family with autosomal dominant cone-rod dystrophy (adCORD).
Genomic DNA and clinical examination results were collected from a Chinese family presenting with adCORD. The candidate disease-causing mutations were screened with whole-exome sequencing (WES) and bioinformatics analyses. Sanger sequencing was used for validation and cosegregation analysis.
A novel frameshift mutation (NM_000554.4; c.538dupG:p.Val180fs) in exon 4 of the CRX gene was identified in all affected individuals in the Chinese family with adCORD. Cosegregation analysis confirmed that this mutation was cosegregated with the disease. This variant, which results in premature termination of the protein, was absent from all public variant databases or internal exome databases.
We used whole-exome sequencing to identify a novel CRX mutation causing adCORD in a Chinese family. This study broadens the known pathogenic mutation spectrum of the CRX gene and shows the potential of WES in identifying the pathogenic mutations of CORD disease.
视锥-视杆营养不良（CORD）是一种具有遗传和表型异质性的遗传性进行性视网膜疾病。在此，我们旨在鉴定一个患有常染色体显性视锥-视杆营养不良（adCORD）的中国家系中患病个体的致病突变。
从一个患有adCORD的中国家系中收集基因组DNA和临床检查结果。采用全外显子组测序（WES）和生物信息学分析筛选候选致病突变。使用桑格测序进行验证和共分离分析。
在患有adCORD的中国家系的所有患病个体中，在CRX基因第4外显子中鉴定出一个新的移码突变（NM_000554.4；c.538dupG:p.Val180fs）。共分离分析证实该突变与疾病共分离。所有公共变异数据库或内部外显子数据库中均未发现这种导致蛋白质过早终止的变异。
我们使用全外显子组测序在一个中国家系中鉴定出一个导致adCORD的新的CRX突变。本研究拓宽了已知的CRX基因致病突变谱，并显示了WES在鉴定CORD疾病致病突变方面的潜力。
