CHM基因变异女性携带者表型和基因型特点

Genotypic and phenotypic characteristics of Chinese carriers with CHM gene variation

目的总结分析中国CHM基因变异女性携带者表型、基因型特点。设计回顾性病例系列。研究对象 北京同仁医院眼科就诊并已确定携带CHM基因变异的5个无脉络膜症(choroideremia,CHM)家系中的6例女性携带者。方法先证者及家系成员均进行详细的眼科检查。用sanger测序、目标区域捕获测序(target exonm sequencing,TES)、实时定量PCR实验确定5个CHM家系的CHM基因致病变异。记录并分析6例女性携带者的临床表现及变异基因分级。主要指标视力、眼底像、光学相干断层扫描图像(OCT)、眼底自发荧光(FAF)及各携带者携带CHM基因变异及其ACMG分级。结果6例携带者来自于5个没有血缘关系的家庭。本组携带者共检测到5种CHM基因变异,包括一个无义变异(p.Y565*),一个剪接位点变异(c.820-1G>T),一个启动子区变异(c.-98C>G)和两个拷贝数异常(Exon1_2 del;Exon5_12 dup)。其中三种变异(p.Y565*,c.-98C>G,Exon5_12 dup)为未曾报道过的新变异,根据ACMG分级标准,该三种变异的致病性评级为致病或可能致病。所有女性携带者平均年龄为(34.00±14.83)岁(范围8~53岁),视力正常,无夜盲、视野缩小等症状。眼底像上显示出点状或片状的视网膜色素减退,可伴有界限清晰的黄色点状沉着。FAF上可见斑驳样片状或马赛克样中低荧光,可伴有点状高荧光。2名携带者进行了3年的随访,视力均稳定,眼底无变化。结论本研究拓展了CHM基因变异的变异谱,与欧美CHM基因变异携带者相比,中国女性携带者视功能损伤及眼底改变更轻微。(眼科,2021,30:211-216)

Objective To summarize and analyze the phenotypic and genotypic characteristics of Chinese carriers with CHM gene variation and compare with foreign carriers.Design Retrospective case series.Participants Six carriers from five choroideremia families with CHM gene variation identifying in the Beijing Tongren Eye Center.Methods The proband and family members underwent detailed ophthalmological examination.Sanger sequencing,target exonm sequencing(TES)and real-time quantitative PCR were used to determine the pathogenic variations of CHM gene in 5 CHM families.Main outcome measures Visual acuity,fundus image,optical coherence tomography image(OCT),fundus autofluorescence(FAF)and gene variations carried by each carrier.Results 6 carriers came from 5 unrelated families.A total of 5 CHM gene variations were detected in these carriers.The average age of all female carriers was(34.00±14.83)years(range 8~53 years old).They had no symptoms,such as decreased vision,night blindness,and visual field contraction.The fundus images showed punctate or flaky hypopigmentation of the retina,which can be accompanied by small yellowish well-defined dots.Mottled flake or mosaic-like low fluorescence could be seen on FAF,with dotted hyperfluorescence.Two carriers were followed up for three years.Their eyesights were stable and their fundus was almost unchanged.Conclusion This study expanded the variation spectrum of CHM gene variations.Compared with European and American carriers with CHM gene variations,the damage of visual function and fundus changes of Chinese female carriers were slighter.(Ophthalmol CHN,2021,30:211-216)