Zhang Shanshan, Li Jie, Li Shujin, Yang Yeming, Yang Mu, Yang Zhenglin, Zhu Xianjun, Zhang Lin
a Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, School of Medicine , University of Electronic Science and Technology of China , Chengdu , Sichuan , China.
b Department of Ophthalmology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine , University of Electronic Science and Technology of China , Chengdu , Sichuan , China.
Ophthalmic Genet. 2018 Aug;39(4):487-491. doi: 10.1080/13816810.2018.1461912. Epub 2018 Apr 25.
Retinitis pigmentosa (RP) is a genetically heterogeneous disease with over 70 causative genes identified to date. However, approximately 40% of RP cases remain genetically unsolved, suggesting that many novel disease-causing mutations are yet to be identified. The purpose of this study is to identify the causative mutations of a Chinese RP family.
Targeted next-generation sequencing (NGS) for a total of 163 genes which involved in inherited retinal disorders were used to screen the possible causative mutations. Sanger sequencing was used to verify the mutations.
As results, we identified two heterozygous mutations: a splicing site mutation c.1407 + 1G>C and a nonsense mutation c. 1957C>T (p.R653X) in phosphodiesterase 6A (PDE6A) gene in the RP patient. These two mutations are inherited from his father and mother, respectively. Furthermore, these mutations are unique in our in-house database and are rare in human genome databases, implicating that these two mutations are pathological.
By using targeted NGS method, we identified a compound heterozygous mutation in PDE6A gene that is associated with RP in a Chinese family.
视网膜色素变性（RP）是一种基因异质性疾病，迄今已鉴定出70多个致病基因。然而，约40%的RP病例在基因层面仍未得到解决，这表明许多新的致病突变尚未被发现。本研究的目的是鉴定一个中国RP家系的致病突变。
采用针对163个参与遗传性视网膜疾病的基因的靶向二代测序（NGS）来筛选可能的致病突变。使用桑格测序法验证这些突变。
结果，我们在该RP患者的磷酸二酯酶6A（PDE6A）基因中鉴定出两个杂合突变：一个剪接位点突变c.1407+1G>C和一个无义突变c.1957C>T（p.R653X）。这两个突变分别遗传自他的父亲和母亲。此外，这些突变在我们的内部数据库中是独特的，在人类基因组数据库中也很罕见，这意味着这两个突变是病理性的。
通过使用靶向NGS方法，我们在一个中国家系中鉴定出PDE6A基因中的一个复合杂合突变，该突变与RP相关。
