Battu Rajani, Jeyabalan Nallathambi, Murthy Praveen, Reddy Kavita S, Schouten Jan Sag, Webers Caroll A
Department of Vitreoretina, Narayana Nethralaya, Bengaluru, Karnataka, India.
Department of Molecular Signaling and Gene Therapy, Grow Research Laboratory, Narayana Nethralaya Foundation, Narayana Nethralaya, Bengaluru, Karnataka, India.
Indian J Ophthalmol. 2016 Dec;64(12):924-929. doi: 10.4103/0301-4738.198866.
This study aims to describe the phenotype and genotype of two Indian families affected with X-linked choroideremia (CHM).
In these two families, the affected individuals and unaffected family members underwent a comprehensive ophthalmic examination including an optical coherence tomography (OCT) and electroretinogram. Blood samples were collected from the families for genetic analysis. Next generation sequencing (NGS) was done using a panel of 184 genes, which covered previously associated genes with retinal dystrophies. Sequencing data were analyzed for the CHM, RPGR, and RP2 genes that have been implicated in CHM and X-linked retinitis pigmentosa (XLRP), respectively. The identified variants were confirmed by Sanger sequencing in available individuals and unrelated controls.
In two unrelated male patients, NGS analysis revealed a previously reported 3'-splice site change c.820-1G>C in the CHM gene in the first family and hemizygous mutation c.653G>C (p.Ser218X) in the second family. The asymptomatic family members were carriers for these mutations. Spectral domain-OCT showed loss of outer retina, preservation of the inner retina, and choroidal thinning in the affected males and retinal pigment epithelial changes in the asymptomatic carriers. The identified mutations were not present in 100 controls of Indian origin. There were no potential mutations found in XLRP-associated (RPGR and RP2) genes.
This report describes the genotype and phenotype findings in patients with CHM from India. The identified genetic mutation leads to lack of Rab escort protein-1 (REP-1) or affects the production of a REP-1 protein that is likely to cause retinal abnormalities in patients.
本研究旨在描述两个患有X连锁性脉络膜视网膜病变（CHM）的印度家庭的表型和基因型。
在这两个家庭中，受影响个体和未受影响的家庭成员接受了全面的眼科检查，包括光学相干断层扫描（OCT）和视网膜电图检查。采集家庭成员的血液样本进行基因分析。使用包含184个基因的面板进行下一代测序（NGS），这些基因涵盖了先前与视网膜营养不良相关的基因。对分别与CHM和X连锁视网膜色素变性（XLRP）相关的CHM、RPGR和RP2基因的测序数据进行分析。在可用个体和无关对照中通过桑格测序确认所鉴定的变异。
在两名无关男性患者中，NGS分析显示第一个家庭的CHM基因中存在先前报道的3'-剪接位点变化c.820-1G>C，第二个家庭中存在半合子突变c.653G>C（p.Ser218X）。无症状家庭成员是这些突变的携带者。光谱域OCT显示受影响男性的外层视网膜缺失、内层视网膜保留以及脉络膜变薄，无症状携带者存在视网膜色素上皮变化。在100名印度裔对照中未发现所鉴定的突变。在与XLRP相关的（RPGR和RP2）基因中未发现潜在突变。
本报告描述了来自印度的CHM患者的基因型和表型发现。所鉴定的基因突变导致Rab护送蛋白-1（REP-1）缺乏或影响REP-1蛋白的产生，这可能导致患者视网膜异常。
