先天性Ⅰ-c型并指畸形家系表型鉴定及遗传分析

Phenotypic Identification and Genetic Analysis of Congenital Syndactyly Family with Ⅰ-c Type

为了探究先天性并指畸形的遗传机制,本研究结合临床体格检查、遗传咨询,X线资料、图片等手段,对收治的疑似Ⅰ-c型并指家系(A家系为五代74人家系,其中病人34人)进行了表型鉴定和遗传分析。根据并指畸形(syndactyly,SD)分类标准,该家系表型经判断属于Ⅰ-c型SD和I-a型SD表型,遗传分析表明,供试家系表现度(在一定的环境中,某一突变个体基因型表达的变异程度)具有一定的差异性,外显率(某一基因型个体显示其预期表型的比率)也不完全,属于常染色体显性遗传方式。研究结果进一步暗示,Ⅳ型SD和三节指节拇指一并多指综合征(triphalangeal thumb polysyndactyly syndrome,TPTPS)致病机制具有遗传同质性(同一种疾病临床表现相同,引起疾病的遗传基础不同),表型-基因型分析提示ZRS区(极化活性区(zone of polarizing activity,ZPA)调控序列(ZPA regulatory sequence,ZRS))轻微表型到严重表型过渡具有一定的连续性。我们的研究为并指的遗传机制的揭示和相关疾病的产前诊断、遗传咨询等工作提供了一定的理论依据。

In order to exp lore the genetic mechanism of congenital syndactyly, this study took clinical examination, genetic counseling, X-ray data, pictures and other means to conduct phenotype identification and genetic analysis for the admitted families with suspected Ⅰ-c type syndactyly（a family contained five generations of 74 members, and there were 34 patients among them）. According to the syndactyly（SD） classification standard,this family belonged to Ⅰ-c type SD and I-a type SD phenotype. The genetic analysis showed that there was a certain difference in the performance of the tested families（in a certain environment, the degree of variation of gene expression of a mutant individual）. The penetrance（the ratio of a single genotype individual to its expected phenotype） was not complete, which belonged to autosomal dominant inheritance. The results of the study further suggested that the pathogenic mechanism of Ⅳ type SD and triphalangeal thumb polysyndactyly syndrome（TPTPS） had genetic homogeneity（the same disease with the same clinical manifestation, but with different causes of genetic bases）. The phenotype-genotype analysis indicated that the ZRS region（zone of polarizing activity（ZPA）regulatory sequence） had a certain transitional continuity from a mild phenotype to a severe phenotype. Our study provided a certain theoretical basis for revealing the genetic mechanism of the syndactyly, the prenatal diagnosis of related diseases and the genetic counseling.