Zhou Qi, Yao Fengxia, Han Xiaoxu, Li Hui, Yang Lizhu, Sui Ruifang
Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Clinical Genetics Laboratory, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Exp Eye Res. 2017 Nov;164:64-73. doi: 10.1016/j.exer.2017.07.016. Epub 2017 Jul 31.
Choroidermia (CHM) is an X-linked chorioretinal disorder caused by mutations in the Rab Escort Protein 1 (Rep-1) gene. Its diagnosis depends on clinical findings and genetic confirmation; however, mutations in Rep-1 gene are not always detected by standard Sanger sequencing. We therefore conducted multiplex ligation-dependent probe amplification (MLPA) and real-time quantitative PCR (QPCR) in cases of Chinese CHM families in which sequencing all the exons and flanking intronic regions of the CHM gene had not identified a mutation or exons could not be amplified. We hypothesized that copy number variation (CNV) within the Rep-1 gene would explain the etiology of choroideremia in these patients. In the eight unrelated families, exon deletions or duplications were detected by MLPA and QPCR in five. Our results showed CNV within the Rep-1 gene could be an important contributor in Chinese CHM patients. Sequencing of the Rep-1 gene supplemented with MLPA is therefore an important diagnostic strategy in choroideremia patients.
脉络膜视网膜病变（CHM）是一种由Rab护送蛋白1（Rep-1）基因突变引起的X连锁性脉络膜视网膜疾病。其诊断依赖于临床发现和基因确认；然而，标准的桑格测序并不总能检测到Rep-1基因的突变。因此，对于中国CHM家系中所有外显子及侧翼内含子区域测序未发现突变或外显子无法扩增的病例，我们进行了多重连接依赖探针扩增（MLPA）和实时定量PCR（QPCR）。我们推测Rep-1基因内的拷贝数变异（CNV）可以解释这些患者脉络膜视网膜病变的病因。在8个无亲缘关系的家系中，通过MLPA和QPCR在5个家系中检测到外显子缺失或重复。我们的结果表明，Rep-1基因内的CNV可能是中国CHM患者的一个重要病因。因此，补充MLPA的Rep-1基因测序是脉络膜视网膜病变患者的重要诊断策略。
