Department of Ophthalmology of Shanghai Tenth People's Hospital, and Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China; Department of Regenerative Medicine, Department of Pharmacology, and Stem Cell Research Center, Tongji University School of Medicine, Shanghai, China.
Department of Ophthalmology of Shanghai Tenth People's Hospital, and Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China.
Exp Eye Res. 2019 Nov;188:107726. doi: 10.1016/j.exer.2019.107726. Epub 2019 Jul 15.
Retinitis pigmentosa (RP) is a group of genetically heterogeneous retinal diseases with more than 80 identified causative genes to date. Mutations in the RHO (rhodopsin, OMIM, 180380) are the most common cause of autosomal dominant RP (adRP) worldwide. RHO is also one of the few RP genes that can cause autosomal recessive RP (arRP). To explore the frequency of RP mutations in Chinese populations, panel-based NGS (next-generation sequencing) screening and Sanger sequencing validation were performed for RP patients from 72 unrelated Chinese families. Here we reported the identified mutations only in the RHO gene. Our results showed that 4 mutations in RHO were detected in 5 (6.94%) of the 72 RP families, including two known missense mutations, c.158C > G (p.P53R) and c.551A > C (p.Q184P), and two novel mutations, c.34delC (p.P12NA) and c.82C > T (p.Q28X). The c.34delC (p.P12NA) mutation was detected in heterozygous state in one patient with intermediate RP phenotype. The c.82C > T (p.Q28X) mutation was found in a homozygous state in one proband with advanced RP phenotype at the age of 32. Clinical examination of the heterozygous carriers of c.82C > T (p.Q28X) in that family showed that the father at the age of 60s experienced no symptoms of RP and normal fundus examinations but displayed reduced electroretinography (ERG) and abnormal visual field. The sister and brother at the age of 30s showed no typical aspects of RP phenotypes. Our results not only expand the mutation spectrum of the RHO gene, but also suggest that the 2 null mutations might play minor dominant effects, leading to less severe and slower retinal degeneration in heterozygous state and more severe phenotype in homozygous state.
色素性视网膜炎（RP）是一组具有 80 多种已鉴定致病基因的遗传性视网膜疾病。迄今为止，RHO（视紫红质，OMIM，180380）突变是全世界常染色体显性遗传 RP（adRP）最常见的原因。RHO 也是少数几个可导致常染色体隐性遗传 RP（arRP）的 RP 基因之一。为了探讨中国人群 RP 突变的频率，我们对 72 个无关的中国家庭的 RP 患者进行了基于面板的下一代测序（NGS）筛选和 Sanger 测序验证。在此，我们仅报告了在 RHO 基因中发现的突变。我们的结果表明，在 72 个 RP 家庭中的 5 个（6.94%）中检测到 RHO 中的 4 种突变，包括两种已知的错义突变，c.158C>G（p.P53R）和 c.551A>C（p.Q184P），以及两种新的突变，c.34delC（p.P12NA）和 c.82C>T（p.Q28X）。c.34delC（p.P12NA）突变在一名具有中间 RP 表型的患者中以杂合状态存在。c.82C>T（p.Q28X）突变在一名 32 岁具有晚期 RP 表型的先证者中以纯合状态存在。该家庭中 c.82C>T（p.Q28X）杂合携带者的临床检查显示，60 多岁的父亲没有 RP 症状，眼底检查正常，但显示视网膜电图（ERG）减弱和视野异常。30 多岁的姐姐和哥哥没有典型的 RP 表型。我们的结果不仅扩展了 RHO 基因的突变谱，还表明这两种无义突变可能发挥轻微的显性作用，导致杂合状态下视网膜变性较轻且较慢，而纯合状态下表型更严重。
