Yu Bingqing, Liu Zhaoxiang, Mao Jiangfeng, Wang Xi, Zheng Junjie, Xiong Shuyu, Cui Mingxuan, Ma Wanlu, Huang Qibin, Xu Hongli, Huang Bingkun, Nie Min, Wu Xueyan
Department of Endocrinology, Peking Union Medical College Hospital, Key Laboratory of Endocrinology, National Health and Family Planning Commission of People's Republic of China, Beijing, China.
Department of Endocrinology, Peking Union Medical College Hospital, Key Laboratory of Endocrinology, National Health and Family Planning Commission of People's Republic of China, Beijing, China.
Steroids. 2017 Oct;126:1-6. doi: 10.1016/j.steroids.2017.07.009. Epub 2017 Aug 1.
17β-Hydroxysteroid dehydrogenase type 3 (17β-HSD3) converts the inactive Δ4-androstenedione (A) to testosterone (T). Its deficiency is the most common testosterone biosynthesis defect that results in 46,XY Disorders Of Sex Development (DSD). However, the disease is difficult to distinguish from other 46,XY DSD for similar clinical phenotypes. Therefore, genetic testing provides good criteria for the diagnosis of the disease. In this study, HSD17B3 gene was examined in 3 unrelated Chinese patients with 46,XY DSD. Direct sequencing and quantitative PCR of HSD17B3 gene revealed the presence of a compound heterozygous mutation (p.I60T/exon1 deletion) in Patient 1, a homozygous (p.I60T) mutation in Patient 2 and a frameshift mutation (p.V25Efs∗54) and an exon1 deletion in Patient 3. All of the mutations have not been reported previously. These novel mutations may expand the mutation database of HSD17B3 gene and provide us new insights into the molecular mechanism of 17β-HSD3 deficiency. It is noteworthy that when direct sequence analysis showed a rare homozygous mutation in patients with non-consanguineous parents, "apparent homozygosity" should be taken into an account and the intragenic deletion should be screened. In addition, when single mutation was found in patients with disease in recessive heredity mode, the intragenic deletion should also be screened.
17β-羟类固醇脱氢酶3型（17β-HSD3）可将无活性的Δ4-雄烯二酮（A）转化为睾酮（T）。其缺乏是导致46,XY性发育障碍（DSD）的最常见的睾酮生物合成缺陷。然而，由于临床表型相似，该疾病很难与其他46,XY DSD区分开来。因此，基因检测为该疾病的诊断提供了良好的标准。在本研究中，对3名无血缘关系的中国46,XY DSD患者的HSD17B3基因进行了检测。HSD17B3基因的直接测序和定量PCR显示，患者1存在复合杂合突变（p.I60T/外显子1缺失），患者2存在纯合（p.I60T）突变，患者3存在移码突变（p.V25Efs∗54）和外显子1缺失。所有这些突变以前均未报道过。这些新的突变可能会扩大HSD17B3基因的突变数据库，并为我们提供有关17β-HSD3缺乏的分子机制的新见解。值得注意的是，当直接序列分析显示非近亲父母的患者存在罕见的纯合突变时，应考虑“表观纯合性”并筛查基因内缺失。此外，当在隐性遗传模式的疾病患者中发现单一突变时，也应筛查基因内缺失。
