【摘要】 目的 阐明3个无脉络膜症(choroideremia, CHM)家系的遗传基础和临床表型。方法 纳入2016～2021年在华中科技大学同济医学院附属协和医院和华中科技大学医院就诊的3个CHM家系共5名患者。受试者均接受详细的眼科检查，包括最佳矫正视力、眼压、眼底彩照、光学相干层析成像(SD-OCT)等。应用全外显子组测序、Sanger测序和二代测序技术对患者潜在的致病突变进行鉴定。结果 5例患者均在10岁以前开始出现夜盲症状。OCT见全部10眼黄斑区出现不同程度的外层视网膜萎缩性改变，8眼(80%)不同程度黄斑囊样病变，7眼(70%)外层视网膜管状结构。2眼最佳矫正视力低于0.02,其黄斑区分别可见严重的囊样病变和脉络膜新生血管(CNV)。在3个家系中分别发现了CHM基因的1个新突变(c.186C>G,p.Y62*)和2个已知突变(c.189+1G>A,c.808C>T)。生物信息学分析预测3个突变都会产生无功能的REP-1截短蛋白。结论 CHM患者中心视力严重下降的可能原因包括黄斑萎缩性改变、囊样病变及脉络膜新生血管。该研究拓宽了CHM基因的突变谱，将有助于患者的诊断、遗传咨询和精准治疗。更多还原

【Abstract】 Objective To reveal the genetic basis and clinical characteristics of three families with choroideremia(CHM).Methods A total of five patients from three CHM families treated in Union Hospital and Hospital affiliated to Huazhong University of Science and Technology from 2016 to 2021 were included.All the participants underwent overall ophthalmologic examinations, including examinations of best corrected visual acuity(BCVA)and intraocular pressure, color fundus photography, spectral domain optical coherence tomography(SD-OCT),etc.Whole-exome sequencing(WES),Sanger sequencing and next-generation sequencing were performed to detect the potential disease-causing mutations.Results All the five patients developed night blindness before the age of ten.Varying degrees of outer retinal atrophic changes in macular area could be seen in all ten eyes.Cystoid macular lesion(CM)and outer retinal tabulation(ORT)were found in 8/10 eyes(80%)and 7/10 eyes(70%)respectively.Severe CM and choroidal neovascularization(CNV)were detected respectively in two eyes with BCVA lower than 0.02.A novel CHM mutation(c.186 C>G,p.Y62*)was identified by WES in pedigree 1.Two known mutations(c.189+1 G>A,c.808 C>T)were identified in pedigree 2 and 3 respectively.All of the three mutations eventually produced a non-functional REP-1 truncated protein according to bioinformatic analysis.Conclusion Loss of visual acuity in CHM patients may be caused by progressive macular atrophy, severe CM and CNV.This study widens the mutation spectrum of CHM gene, which will be beneficial to the diagnosis, genetic counseling and precise treatment of CHM patients.更多还原