一种导致完全性雄激素不敏感综合征的AR基因移码突变的鉴定

A novel deletion mutation in AR gene causes complete androgen insensitivity syndrome in a Chinese family

目的 对1个男性假两性畸形完全性雄激素不敏感综合征的家系雄激素受体（androgen receptor,AR）基因进行突变检测,并分析其致病原因.方法 用PCR扩增及DNA测序等技术分析男性假两性畸形先证者候选基因AR的外显子及外显子内含子接头序列,根据检测到的突变位点情况,检测患者及其家系其他成员的相应DNA区段的碱基序列.结果 先证者及其家庭成员共3例患者均为AR基因1910delA的移码突变.其母亲为AR基因突变杂合子,是此疾病的携带者.该突变导致AR基因的N637I（AAU→AUC）、L638＊（CTG→TGA）改变,导致AR蛋白283个氨基酸的截短.正常人群未发现该移码突变,该突变尚未见文献报道.结论 基因水平确定了该家系为AR基因突变引起的完全性雄激素不敏感综合征男性假两性畸形家系,同时发现了1种AR基因病理性新突变.

Objective To identify the mutation of the androgen receptor （AR） gene in a complete androgen insensitivity family. Methods DNA was extracted from peripheral blood samples from family members in the family. PCR and DNA sequencing were then employed to detect the mutation of AR gene.Results A single nucleotide deletion of nucleotide A in exon 4 of the AR gene （1910delA） was detected in all the three patients in this family, which lead to Asn637Ile and Lys638stop. This mutation was also found in the mother （heterozygote） but was not observed in the normal controls. Conclusion The 1910delA mutation of the AR gene is a novel mutation that leads to complete androgen insensitivity syndrome.