蒙古族X连锁先天缺失牙/头发卷曲家系EDA基因新错义突变的发现  

A novel missense mutation (R65G)of EDA gene in a mongolian family with X-linked congenital anodontia/wavy hair

作　　者：白海花[1] 张昕原[1] 邱长春[2] 顾明亮[2] 吉日木图[1] 赵宏林[1] 赵文海[1] 侯淑琴[2] 周文郁[2] 吴柒柱[1] 白玉华[1] 

机构地区：[1]内蒙古民族大学,通辽028000 [2]中国医学科学院中国协和医科大学基础医学研究所医学分子生物学国家重点实验室,北京100005

出　　处：《基础医学与临床》2004年第5期509-513,共5页Basic and Clinical Medicine

基　　金：国家自然科学基金 (30 393139);东营协和基因技术有限责任公司资助

摘　　要：为鉴定蒙古族X连锁先天缺失牙 /头发卷曲家系外胚层发育不全无汗综合征致病基因 (EDA)突变类型及其与表型的关系 ,本文以七代患有先天缺失牙的蒙古族大家系为研究对象 ,应用聚合酶链反应产物直接测序 (PCR/Sequencing)分析每个成员EDA基因第一外显子碱基突变及其部位。测序结果显示 ,先证者及其他男性患者EDA基因第一外显子 193位的胞嘧啶被鸟嘌呤取代 ,均为 193G/G纯合基因型 ,193C→G颠换是一种新的错义突变 ,导致胞外区 6 5精氨酸转变为甘氨酸 (R6 5G)。先症者母亲Ⅳ 8为 193C/G杂合基因型 ,牙齿正常。携带 193G/C杂合基因型女性临床表型为Ⅴ 3表现 11、2 1、31、4 1缺如 ,Ⅴ 31表现 12、2 2缺如 ,两者均伴有头发卷曲 ,而Ⅴ 1、Ⅴ 6、Ⅴ 8、Ⅴ 11、Ⅴ2 0、Ⅴ 4 6及Ⅳ 10、Ⅵ 3等牙齿数目及形态均无明显异常 ,头发无卷曲。综上所述 ,该蒙古族大家系中EDA基因第一外显子 193位C→G颠换引起的错义突变 ,是导致其发病的主要分子机制之一。但携带To identify the relationship of mutation type and phenotype of anhydrite ectodermic dysplasia (EDA) gene in a Mongolian family with X-linked congenital anodontia/wavy hair. Study objects were a long family with congenital anodontia in seven generations,among them 16 members are phenotype anomaly (male 14,female 2).The first to nighth exons EDA genes of all members affected and normal were analysed with the Polymerase Chain Reaction and Squencing (PCR/Sequencing). A C193→G transvertion in the first exon of EDA gene was shown in the proband and other males affected and all were 193 G/G homogenous genotype.The C193→G transvertion is a new missense mutation which resulted in an Arg65Gly(R65G) substitution in the extracellularly segment of protein product of the gene.The proband's mother Ⅳ8 carries 193C/G heterozygous gene ,and her teeth are normal.Among female heterozygous mutation of 193→G,Ⅴ3 lacks 11?21?31?41,Ⅴ31 lacks 12?22,Ⅴ1Ⅴ6Ⅴ8Ⅴ11Ⅴ20Ⅴ46Ⅳ10Ⅵ3 are normal terms of number and morphology of the teeth.The missense mutation of C193→G transvertion of the first exon of EDA gene in the family is one of the main molecular basis of tooth agenesis.The phenotype difference of the female heterozygous with 193→G mutation and the expressivity difference of male affected remain to be studied.

关 键 词：蒙古族 X连锁先天缺失牙 头发卷曲家系 EDA基因 基因型 表型 

分 类 号：R596.1[医药卫生—内科学]