一个双侧耳甲腔型小耳畸形家系遗传学及临床表型分析  

Genetic analysis and clinical phenotype of a family with bilateral concha-type microtia

作　　者：钱会利[1] 张利难 贾阳[2] 侯秀英[1] 张宝林[1] Qian Huili;Zhang Linan;Jia Yang;Hou Xiuying;Zhang Baolin(Plastic Surgery Department of the First Hospital of Shanxi Medical University,Taiyuan 030001,China;Department of Plastic Surgery,the Second Hospital of Hebei Medical University,Shijiazhuang 050004,China)

机构地区：[1]山西医科大学第一医院整形科,太原030001 [2]河北医科大学第二医院整形外科,石家庄050004

出　　处：《中华整形外科杂志》2024年第2期163-168,共6页Chinese Journal of Plastic Surgery

摘　　要：目的:对1个中国汉族非综合征型双侧耳甲腔型小耳畸形家系进行致病变异检测及临床表型分析。方法:2022年6至12月于山西医科大学第一医院整形外科收集1个中国汉族非综合征型双侧小耳畸形家系成员的临床资料以及外周血样本,提取先证者DNA利用全基因组测序(WGS)筛选可能的候选变异。采用荧光定量PCR验证候选拷贝数变异(CNV)在先证者及其表型正常的配偶和患病儿子的存在情况,并分析其与表型的相关性。结果:该家系共4代9人,含4例小耳畸形患者,收集到其中3人外周血样本,分别为先证者、先证者配偶(表型正常)、先证者的儿子(患病)。家系内患者表现为非综合征型双侧耳甲腔型小耳畸形。WGS在先证者检测到HMX1和CPZ基因间区的拷贝数增加,重复区域累及HMX1基因远程增强子进化保守区域(ECR),该变异存在于先证者及其患病的儿子,其配偶临床表型正常,不存在ECR的CNV改变。结论:累及HMX1远程增强子ECR的CNV重复可能与该家系的双侧耳甲腔型小耳畸形有关。Objective To detect pathogenic mutation in a Chinese family affected with isolated bilateral microtia.Methods During 2022 June to December,one Chinese Han family with non-syndromic bilateral microtia was recruited at the First Hospital of Shanxi Medical University.The clinical data and peripheral blood samples were collected from the family members.Whole genome sequencing(WGS)was performed in the proband to screen all candidate variants.Quantitative PCR was applied to identify the candidate copy number variation(CNV)among the proband,the unaffected wife and the affected son to demonstrate the association between candidate variant and phenotype.Results The patients in the family had non-syndromic bilateral concha-type microtia.WGS detected the duplication in the intergenic region of HMX1 and CPZ gene in the proband,which involved the evolutionarily conserved region(ECR).Both the proband and his affected son carried the CNV,while his unaffected wife did not have this variation.Conclusion Duplications involving the long range HMX1 enhancer ECR are associated with the bilateral concha-type microtia in this family.

关 键 词：先天性小耳畸形 耳甲腔型 全基因组测序 进化保守区域 HMX1基因 拷贝数变异 增强子 

分 类 号：R764.7[医药卫生—耳鼻咽喉科]