一例以智力低下为首发症状的面肩肱型肌营养不良患儿D4Z4区的变异分析  

Analysis of D4Z4 mutation in a child with facioscapulohumeral muscular dystrophy presented initially as mental retardation

作　　者：田杨 侯池 杨志晓[2] 曹彬彬 张巍 陈文雄 Tian Yang;Hou Chi;Yang Zhixiao;Cao Binbin;Zhang Wei;Chen Wenjciong(Guangzhou Women and Children 9s Medical Center,Guangzhou,Guangdong 510000,China;Children7s Hospital Affiliated to Zhengzhou University,Zhenzhou^Henan 450018,China;Baylor College of Medicine,Houston,TX 77030,USA;AmCare Genomics Lab Co.Ltd.,Guangzhou,Guangdong 510300,China)

机构地区：[1]广州市妇女儿童医疗中心,510000 [2]郑州大学附属河南省儿童医院,450018 [3]贝勒医学院,美国休斯敦TX77030 [4]广州嘉检医学检测有限公司,510300

出　　处：《中华医学遗传学杂志》2020年第2期150-152,共3页Chinese Journal of Medical Genetics

摘　　要：目的鉴定一例以智力障碍为首发症状的面肩肱型肌营养不良(facioscapulohumeral muscular dystrophy,FSHD)患儿4q35上D4Z4区域的致病变异。方法对患儿进行韦氏智力检测,并收集其临床资料进行综合分析。提取患儿及其父母的外周血DNA,先采用医学外显子组二代测序和拷贝数变异检测,之后应用分子梳法鉴定其D4Z4重复单元的缩短情况并鉴定其来源。结果患儿总体智商估计值为41,言语理解指数估计值为45,知觉推理指数估计值为520医学外显子组测序和拷贝数变异检测未发现患儿携带致病变异,分子梳检测结果表明患儿D4Z4区的长度为5.2kb,重复单元数为2,患儿的父母均未检测到相同的变异。结论D4Z4重复单元只有2个可能是患儿智力低下和FSHD的致病原因。分子梳检测能够鉴定此重复单元的数目和来源,有助于明确诊断。Objective To identify pathological mutation of D4Z4 in a child with facioscapulohumeral muscular dystrophy(FSHD)presented initially as mental retardation.Methods Wechsler Intelligence Scale for Children Revised in China(WISC-JV)was used to assess the patient's IQ Other clinical data was also collected.With genomic DNA extracted from peripheral blood samples,the child and his parents were subjected to medical exome sequencing and copy number variation analysis by next generation sequencing(NGS).The D4Z4 repeats and their origin source were determined by molecular combing.Results By the WISC-IV test,the child was found to have a total IQ of 41,with a speech comprehension IQ of 45,and perceptual inference index IQ of 52.No pathological mutation was detected by NGS.By molecular combing method,the child was found to carry a D4Z4 spanning 5.2 kb with a copy number of 2.Analysis of his parents indicate that the mutation was de novo.Conclusion The D4Z4 copy number variation may account for the FSHD and mental retardation in the child.The molecular combing method can be used to identify the number of repeat units and facilitate the diagnosis of FSHD.

关 键 词：智力低下 面肩肱肌型营养不良 D4Z4重复单元 分子梳 

分 类 号：R74[医药卫生—神经病学与精神病学]