【摘 要】
：
性腺发育不良(Disorders of sex development,DSD)是性决定与性分化过程中出现异常的一类疾病,该类疾病仅通过生化激素水平鉴别有时较困难,从遗传学角度检测病因可为DSD的临床诊治提供指导及依据.目的：在DSD病人中通过二代测序对80个DSD相关基因进行检测,并探究遗传学病因.方法：利用Ampliseq技术构建涵盖80个DSD基因外显子区域(覆盖率95％)的文库并在Ion
【机 构】
：
上海交通大学医学院附属新华医院,上海市儿科医学研究所
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性腺发育不良(Disorders of sex development,DSD)是性决定与性分化过程中出现异常的一类疾病,该类疾病仅通过生化激素水平鉴别有时较困难,从遗传学角度检测病因可为DSD的临床诊治提供指导及依据.目的：在DSD病人中通过二代测序对80个DSD相关基因进行检测,并探究遗传学病因.方法：利用Ampliseq技术构建涵盖80个DSD基因外显子区域(覆盖率95％)的文库并在Ion Torrent PGM平台上测序,测序结果经Torrent Suite分析后,依据ACMG指南对变异进行解读,并对部分变异进行Sanger测序验证.结果：在36例临床诊断为DSD的病人中,有8例病人携带致病性变异(22.2％),2例病人携带可能致病变异(5.6％),6例病人携意义不明确的变异(16.7％).发现的致病性/可能致病性变异包括：SRD5A2的2个错义突变(c.680G＞A,c.607G＞A),1个移码突变(c.656delT)及1个无义突变(c.16C＞T)；GNRHR的2个错义突变(c.521A＞G,c.415C＞T)；KAL1的2个无义突变(c.1267C＞T,c.1270C＞T)；DAX-1的2个错义突变(c.871T＞G,c.376G＞A)和AR的1个错义突变(c.2610T＞G).结论：36例病人中的8例(22.2％)可通过二代测序基本明确遗传学诊断,包括3例类固醇5α还原酶缺乏症,2例Kallman综合症,1例促性腺激素释放激素受体缺陷,1例雄激素不敏感综合症和1例DAX-1缺陷.通过二代测序明确DSD的遗传学病因可帮助疾病的分型,对疾病的诊断、特异性治疗及预后均有重要意义.
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