State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, PR China.
Biochem Biophys Res Commun. 2010 Oct 8;401(1):42-7. doi: 10.1016/j.bbrc.2010.09.004. Epub 2010 Sep 9.
Mutations in the rhodopsin gene (RHO) are suggested to be the most common cause of autosomal dominant retinitis pigmentosa (RP). However, the exact spectrum and frequency of RHO mutations in different forms of RP has not been well defined, especially in Chinese populations. In this study, direct cycle sequencing was used to analyze all five coding exons and adjacent intronic regions of RHO in 248 Chinese probands with different forms of non X-linked RP. Eight heterozygous nucleotide changes were detected, including two novel mutations (c.628G>T, p.Val210Phe; c.945C>G, p.Asn315Lys) and six known mutations (c.527C>T, p.Ser176Phe; c.568G>T, p.Asp190Tyr; c.768_770delCAT, p.Ile256del; c.1040C>T, p.Pro347Leu; c.310G>A, p.Val104Ile; c.895G>T, p.Ala299Ser), in 14 probands (nine isolated cases, three from autosomal dominant families, and three from autosomal recessive families). Of the eight mutations, seven were missense changes and one was a small deletion. Six may be pathogenic mutations, and two others (c.310G>A, c.895G>T) may not be causative on their own. The p.Ala299Ser change was present in six of the 248 probands with RP but only in one of 384 normal controls, while the p.Val104Ile was present in two probands but none of the 384 controls. Our results demonstrate an overview of the spectrum and frequency of RP RHO mutations in a Chinese population and emphasize that RHO mutations in isolated RP are not uncommon.
视紫红质基因(RHO)突变被认为是常染色体显性遗传视网膜色素变性(RP)最常见的原因。然而,不同形式的 RP 中 RHO 突变的确切谱和频率尚未得到很好的定义,特别是在中国人群中。在这项研究中,我们使用直接循环测序分析了 248 例不同形式非 X 连锁 RP 中国先证者的 RHO 所有五个编码外显子和相邻内含子区域。共检测到 8 个杂合核苷酸变化,包括 2 个新突变(c.628G>T,p.Val210Phe;c.945C>G,p.Asn315Lys)和 6 个已知突变(c.527C>T,p.Ser176Phe;c.568G>T,p.Asp190Tyr;c.768_770delCAT,p.Ile256del;c.1040C>T,p.Pro347Leu;c.310G>A,p.Val104Ile;c.895G>T,p.Ala299Ser),在 14 个先证者(9 个孤立病例、3 个常染色体显性家族和 3 个常染色体隐性家族)中发现。这 8 个突变中,有 7 个是错义突变,1 个是小缺失。其中 6 个可能是致病性突变,另外 2 个(c.310G>A,c.895G>T)可能不是致病的。p.Ala299Ser 突变在 248 例 RP 先证者中有 6 例,而在 384 例正常对照中只有 1 例,而 p.Val104Ile 突变在 2 例先证者中出现,但在 384 例对照中均未出现。我们的结果展示了中国人群中 RP RHO 突变的谱和频率的概述,并强调孤立性 RP 中的 RHO 突变并不罕见。