Kim Ja Hye, Kang Eungu, Heo Sun Hee, Kim Gu-Hwan, Jang Ja-Hyun, Cho Eun-Hae, Lee Beom Hee, Yoo Han-Wook, Choi Jin-Ho
Department of Pediatrics, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Republic of Korea.
Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Mol Cell Endocrinol. 2017 Mar 15;444:19-25. doi: 10.1016/j.mce.2017.01.037. Epub 2017 Jan 24.
Disorders of sex development (DSD) vary phenotypically and are caused by a number of genetic etiologies. This study investigated the genetic etiology of DSD patients using targeted exome sequencing of 67 known DSD-associated genes in humans. This study included 37 patients with 46, XY DSD and seven patients with 46, XX DSD. We identified known pathogenic mutations or deletion in nine (20.5%) patients in the AR, CYP17A1, SRD5A1, and DMRT1/2 genes. Novel variants were identified in nine patients (20.5%) in the AR, ATRX, CYP17A1, CHD7, MAP3K1, NR5A1, and WWOX genes. Among them, four patients harbored pathogenic or likely pathogenic variants, while the remaining five patients (11.4%) had variants of uncertain significance. We were able to make a genetic diagnosis in 29.5% of patients with pathogenic or likely pathogenic mutations. Targeted exome sequencing is an efficient tool to improve the diagnostic yield of DSD, despite its phenotypic and genetic heterogeneity.
性发育障碍（DSD）在表型上存在差异，由多种遗传病因引起。本研究通过对人类67个已知的与DSD相关基因进行靶向外显子组测序，调查了DSD患者的遗传病因。本研究纳入了37例46, XY DSD患者和7例46, XX DSD患者。我们在AR、CYP17A1、SRD5A1和DMRT1/2基因中，在9例（20.5%）患者中鉴定出已知的致病突变或缺失。在AR、ATRX、CYP17A1、CHD7、MAP3K1、NR5A1和WWOX基因中，在9例（20.5%）患者中鉴定出新型变异。其中，4例患者携带致病或可能致病的变异，其余5例患者（11.4%）具有意义未明的变异。我们能够在29.5%携带致病或可能致病突变的患者中做出基因诊断。尽管DSD存在表型和遗传异质性，但靶向外显子组测序是提高DSD诊断率的有效工具。
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