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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 193G突变等位基因杂合基因型女性表型各异以及男性患者表现度不一致的机制有待深入研究
In order to identify the type of EDA mutation and its relationship with phenotype in Mongolian X-linked congenital absence of tooth / hair curly family, in this paper, seven generations of Mongolian people with congenital absence of tooth As the research object, PCR-Sequencing was used to analyze the base mutation and location of the first exon of EDA gene in each member. The sequencing results showed that the cytosine at position 193 of the first exon of EDA gene was replaced by guanine in the probands and other male patients, which were all 193G / G homozygous genotypes. 193C → G transversion was a new missense Mutation, resulting in the conversion of 6 5 arginine to glycine (R6 5G) in the extracellular domain. First symptom mother Ⅳ 8 193C / G heterozygous genotype, normal teeth. The clinical phenotype of 193G / C heterozygous genotypes was Ⅴ 3, with 11,2 1,31,4 1 absence, Ⅴ 31 12,2 2 absence, both with curly hair, and Ⅴ 1, Ⅴ 6, Ⅴ 8, Ⅴ 11, Ⅴ 20, Ⅴ 4 6 and Ⅵ 10, Ⅵ 3 and other teeth number and shape no obvious abnormalities, hair curly. In conclusion, the missense mutation caused by the C → G transversion at position 193 of the first exon of the EDA gene in the Mongolian pedigree is one of the major molecular mechanisms leading to its occurrence. However, the 193G mutant allele heterozygous genotype female phenotype and male patients with inconsistent performance mechanism remains to be further studied