Novel mutations of HSD17B3 in three Chinese patients with 46,XY Disorders of Sex Development

作者：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^*

来源：Steroids, 2017, 126: 1-6.

DOI：10.1016/j.steroids.2017.07.009

• 17 beta-Hydroxysteroid dehydrogenase type 3 deficiency
• 46,XY Disorders of Sex Development
• HSD17B3 gene mutations

17 beta-Hydroxysteroid dehydrogenase type 3 (17 beta-HSD3) converts the inactive Delta 4-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/exonl deletion) in Patient 1, a homozygous (p.I60T) mutation in Patient 2 and a frameshift mutation (p.V25Efs*54) and an exoni 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 17 beta-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.

• 出版日期2017-10
• 单位中国医学科学院北京协和医院