完全型雄激素不敏感综合征雄激素受体基因突变分析

目的 对完全型雄激素不敏感综合征一家系雄激素受体(androgen receptor,AR)基因进行突变检测;并对发现突变的基因进行分析.方法 应用PCR扩增、DNA序列测定等技术分析所有AR基因外显子及其邻近DNA序列片段;应用核苷酸内切酶诊断方法观察其是否存在于正常人群;应用跨物种比对方法探讨突变所在位置的保守性.结果 3例患者AR基因第4外显子均发生E681D(GAG→GAT)错义突变,患者母亲为此突变杂合子携带者;患者父亲未见异常;正常人群未发现AR基因E681D突变;681位谷氨酸在不同物种间高度保守.结论 AR基因E681D(GAG→GAT)突变可能是导致完全型雄激素不敏感综合征新的突变方式.

Mutation analysis of the androgen receptor gene in a complete androgen insensitivity syndrome family

Objective To study the mutation of the androgen receptor gene in a family with complete androgen insensitivity syndrome and to explore the pathogenicity of the mutation.Methods PCR and DNA sequencing were performed to study the AR gene mutation;Mbo I restriction endonuclease was used to detect existence of the mutation in normal controls;conservation of the mutation site was analyzed by comparison of the sequence of amino acid among different species.Results The DNA sequence of the three patients contained the same substitution of a single nucleotide on codon 681 GAG to GAT of exon 4,which located in the ligand binding domain of the AR receptor and led to substitution of glutamic acid to aspartic acid in the AR receptor.Their mother was heterozygote of E681D.E681D was not observed in the normal controls.The E681 site was extremely conservative in different species.Conclusion The E681D mutation of the AR gene is a novel mutation of leading to complete androgen insensitivity syndrome.