一个先天性肌营养不良症家系的POMT1基因突变鉴定与产前诊断  

Analysis of POMT1 gene mutation in a pedigree affected with congenital muscular dystrophy

作　　者：陈晨[1] 梅世月[1] 朱朝锋[1] 任依琳 孔祥东[1] 

机构地区：[1]郑州大学第一附属医院产前诊断中心,450052

出　　处：《中华医学遗传学杂志》2018年第1期78-80,共3页Chinese Journal of Medical Genetics

摘　　要：目的确定1个先天性肌营养不良症（congenital muscular dystrophy, CMD）家系的POMT1致病基因突变，并对该家系中孕11周的胎儿进行产前诊断。方法收集1例CMD患者及其表型正常父母的外周血标本，抽取母亲孕11周胎儿的绒毛标本。采用PCR扩增POMT1基因的第19和第20外显子，对PCR产物进行双向测序检测基因突变，明确致病突变来源后，进一步对胎儿进行产前诊断。结果先证者POMT1基因第19外显子检测到C．1939G〉A（P．Ala647Thr）杂合错义突变，来自其母亲；第20外显子检测到C．2141delG（P．Trp714Ter）杂合框移突变，导致蛋白质翻译的提前终止，该突变来自其父亲。产前诊断结果显示胎儿携带POMT1基因第19外显子c．1939G〉A杂合错义突变，推测其为与母亲相同POMn基因致病突变携带者的可能性大。结论POMT1基因第19外显子C．1939G〉A错义突变和第20外显子C．2141delG移码突变的复合杂合突变可能是该CMD家系的致病原因，符合常染色体隐性遗传的规律，通过基因产前诊断可以有效阻止致病突变的传递。Objective To analyze mutation of POMT1 gene in a Chinese family affected with congenital muscular dystrophy （CMD）. Methods Peripheral blood samples of the family including one affected and two unaffected individuals, in addition with chorionic villous sample from the fetus, were eolleeted. PCR was used to amplify exons 19 and 20 of thePOMT1 gene, and the products were sequenced directly. Based on the result of genetic testing, prenatal diagnosis of the fetus was attained. Results The proband was found to carry a heterozygous missense mutation c. 1939G〉A （p. Ala647Thr） in exon 19 of the POMT1 gene inherited from the mother and a heterozygous frameshift mutation c. 2141delG （p. Trp714Ter） in exon 20 inherited from the father. Prenatal diagnosis revealed that the fetus has carried the c. 1939G2〉A （p. Ala647Thr） missense mutation. With the disease causing mutation, the fetus was predicted to have similar phenotype as its mother. Couclusion The compound heterozygous mutations of c. 1939G〉A （p. Ala647Thr） and c. 2141delG （p. Trp714Ter） probably underlie the CMD in this family. Based on the result, prenatal diagnosis may be provided.

关 键 词：先天性肌营养不良症 POMT1基因 基因突变 产前诊断 

分 类 号：R746.2[医药卫生—神经病学与精神病学]