携带ECM1基因致病变异类脂蛋白沉积症患者的基因变异与临床特征分析  

Genotype and clinical phenotype analysis of lipoid proteinosis patients with pathogenic variants in ECM1 gene

作　　者：常昊昱 许可 谢玥 石婕 张昕 田露 李杨 Chang Haoyu;Xu Ke;Xie Yue;Shi Jie;Zhang Xin;Tian Lu;Li Yang(Beijing Institute of Ophthalmology,Beijing Tongren Eye Center,Beijing Tongren Hospital,Capital Medical University,Beijing Key Laboratory of Ophthalmology and Visual Sciences,Beijing 100005,China)

机构地区：[1]首都医科大学附属北京同仁医院,北京同仁眼科中心北京市眼科研究所眼科学与视觉科学北京市重点实验室,100005

出　　处：《眼科》2021年第5期374-378,共5页Ophthalmology in China

摘　　要：目的描述中国人携带ECM7基因变异导致类脂蛋白沉积症患者的临床表现和致病基因变异特点。设计回顾性病例系列。研究对象携带ECM7基因致病变异类脂蛋白沉积症患者北京同仁医院2例和目前中国已报道的14例。方法回顾患者.的临床表现。采集患者及其父母的外周血样提取基因组DNA,Sanger测序法对先证者进行ECM1基因序列分析,用多种生物信息学分析软件预测检出可疑致病变异的致病性,并行家系共分离验证。主要指标ECM1基因变异、眼部体征、声音改变、皮肤黏膜异常情况。结果16例患者平均年龄(20.9±13.8)岁。所有患者均出现不同程度的声音嘶哑和眼睑串珠样丘疹的表现。8例患者自出生起发现声音嘶哑,2例出现在婴儿期,6例出现在幼儿期。其中2例患者在上下睑均出现眼睑串珠样丘疹,另14例患者仅在上脸发现。这些患者共检出ECM7基因14种致病变异,包括5种错义变异、4种移码变异、3种无义变异、1种剪接位点变异、1种大片段缺失。错义变异是检出变异的主要类型,占变异总数的35.7%。变异集中发生在6、7外显子,变异频次占比为58.7%。位于第6外显子的p.(Cys220Gly)变异是中国人群的变异热点。结论类脂质蛋白沉积症患者均有声音嘶哑和眼脸串珠样丘疹的典型表现。中国人ECM1基因变异集中在6、7外显子,热点为第6外显子的p.(Cys220Gly)。Objective To describe the clinical manifestations and characteristics of pathogenic gene variants in Chinese patients carrying ECM1 gene variants causing lipoid proteinosis.Design Retrospective case series.Participants 16 Chinese probands(2 patients from Beijing Tongren Hospital and 14 patients from 11 recent literatures)with pathogenic variants in ECM1 gene.Methods The clinical manifestations of the patients were reviewed.Peripheral blood samples of patients and their parents were collected to extract genomic DNA,and Sanger sequencing was used to sequence the ECM1 gene in probands.Multiple bioinfbrmatics analysis software was used to predict the pathogenicity of the suspected pathogenic variants and the pathogenic variants were performed the co-segregated analysis.Main Outcome Measures ECM1 gene variants,ocular signs,voice changes,and skin mucosal abnormalities.Results The mean age of the 16 patients was(20.9±13.8)years,and all patients presented with varying degrees of hoarseness and eyelid bead-like papules.8 patients had hoarseness since birth,2 in infancy and 6 in early childhood.The missense variants were the main types of detected variants,accounting for 35.7%of the total variants.The variants were concentrated in exons 6 and 7,accounting for 58.7%of all variants.The p.(Cys220Gly)variant located in exon 6 was the hot spot of variants in the Chinese population.Conclusion Patients with lipoid proteinosis all have typical clinical features of hoarseness and eyelid bead-like papules.Chinese ECM1 gene variants are concentrated in exons 6 and 7,and the hot spot is p.(Cys220Gly)of exon 6.

关 键 词：类脂蛋白沉积症 ECM1基因 基因变异 

分 类 号：R725.9[医药卫生—儿科] R596[医药卫生—临床医学]