Ma Li, Sheng Xun-Lun, Li Hui-Ping, Zhang Fang-Xia, Liu Ya-Ni, Rong Wei-Ning, Zhang Jian-Ling
Ningxia Eye Hospital, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan 750011, Ningxia Hui Autonomous Region, China.
Int J Ophthalmol. 2013 Aug 18;6(4):430-5. doi: 10.3980/j.issn.2222-3959.2013.04.04. eCollection 2013.
To screen mutations in the retinitis pigmentosa 1 (RP1) gene and the rhodopsin (RHO) gene in Chinese patients with retinitis pigmentosa sine pigmento (RPSP) and describe the genotype-phenotype relationship of the mutations.
Twenty affected, unrelated Chinese individuals with RPSP (4 autosomal dominant RPSP, 12 autosomal recessive RPSP and 4 unknown inheritance pattern) were recruited between 2009 and 2012. The clinical features were determined by complete ophthalmologic examinations. Polymerase chain reaction (PCR) and direct DNA sequencing were used to screen the entire coding region and splice junctions of the RP1 gene and the RHO gene. The cosegregation analysis and population frequency studies were performed for patients with identified mutations.
Five variants in the RP1 gene and one in the RHO gene were detected in 20 probands. Four missense changes (rs444772, rs446227, rs414352, rs441800) and one non-coding variant (rs56340615) were common SNPs and none of them showed a significant relationship with RPSP. A missense mutation p.R1443W was identified in the RP1 gene in three affected individuals from a family with autosomal dominant RPSP and was found to cosegregate with the phenotype in this family, suggestive of pathogenic. In addition, population frequency analysis showed the p.R1443W mutation was absent in 300 healthy controls.
The identification of p.R1443W mutation cosegregating in a family with autosomal dominant RPSP highlights an atypical phenotype of the RP1 gene mutation, while RHO gene is not associated with the pathogenesis of RPSP in this study. To our knowledge, this is the fist mutation identified to associate with RPSP.
筛查中国无色素性视网膜色素变性（RPSP）患者视网膜色素变性1（RP1）基因和视紫红质（RHO）基因的突变情况，并描述这些突变的基因型-表型关系。
2009年至2012年间招募了20名患有RPSP的无血缘关系的中国患者（4例常染色体显性RPSP、12例常染色体隐性RPSP和4例遗传模式不明）。通过全面的眼科检查确定临床特征。采用聚合酶链反应（PCR）和直接DNA测序对RP1基因和RHO基因的整个编码区及剪接位点进行筛查。对已鉴定出突变的患者进行共分离分析和群体频率研究。
在20名先证者中检测到RP1基因的5个变异和RHO基因的1个变异。4个错义改变（rs444772、rs446227、rs414352、rs441800）和1个非编码变异（rs56340615）为常见单核苷酸多态性（SNP），它们均与RPSP无显著关系。在一个常染色体显性RPSP家族的3名患病个体中鉴定出RP1基因的一个错义突变p.R1443W，且发现该突变与该家族的表型共分离，提示其具有致病性。此外，群体频率分析显示300名健康对照中不存在p.R1443W突变。
在一个常染色体显性RPSP家族中鉴定出共分离的p.R1443W突变，突出了RP1基因突变的非典型表型，而在本研究中RHO基因与RPSP的发病机制无关。据我们所知，这是首个被鉴定出与RPSP相关的突变。
