完全型雄激素不敏感综合征雄激素受体基因突变的鉴定与分析

Identification of a novel frameshift mutation of human androgen receptor gene in a patient featuring completeandrogen insensitivity syndrome

目的对1例完全型雄激素不敏感综合征（completeandrogeninsensitivitysyndrome，CAIS）患者的雄激素受体（androgenreceptor，AR）基因进行分析，寻找潜在的突变位点，并进一步分析其发病原因。方法提取患者外周血全基因组DNA，扩增位于X染色体AR基因8个外显子及邻近外显子与内含子剪切位点DNA序列，对扩增产物直接进行DNA序列测定，与GenBank中的基因序列进行比对。结果该患者AR基因在第6外显子核苷酸序列3507位点缺失一个碱基C而引起移码突变，致使在第808位密码子出现终止密码子（TGA）使得翻译提前终止形成截短的雄激素受体蛋白。该突变可能诱导雄激素受体结合能力发生功能七的变异，导致CAIS的发生。结论AR基因第6外显子核苷酸序列3507位点缺失碱基C引起的移码突变是一种导致CAIS新的基因突变方式，该研究丰富了AR基因突变谱，为了解CAIs的发病机制提供了新的依据。

Objective To identify potential mutation of human androgen receptor （AR） gene in a patient with complete androgen insensitivity syndrome （CAIS）. Methods DNA sequences of 8 exons and exon/intron boundaries of the AR gene were amplified with PCR and directly sequenced. Results DNA sequencing revealed a frameshift mutation due to deletion of nucleotide C at position 3507 in exon 6, which gave rise to a stop codon resulting premature termination for translation. Conclusion A novel frameshift mutation in exon 6 of AR gene probably underlies the disease in our patient.