Yang Zuwei, Ye Lei, Wang Wei, Zhao Yu, Wang Wencui, Jia Huiying, Dong Zhiya, Chen Yuhong, Wang Weiqing, Ning Guang, Sun Shouyue
Shanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, PR China.
Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, PR China.
J Steroid Biochem Mol Biol. 2017 Nov;174:141-145. doi: 10.1016/j.jsbmb.2017.08.012. Epub 2017 Aug 25.
17β-Hydroxysteroid dehydrogenase 3 deficiency is a rare autosomal recessive cause of 46, XY disorders of sex development resulting from HSD17B3 gene mutations, however, no case has been reported in East Asia. The aim of this study was to report three Chinese 46, XY females with 17β-HSD3 deficiency in a single center and perform a systematic review of the literature. Clinical examination, endocrine evaluation and HSD17B3 gene sequencing were performed in the three Chinese phenotypically females (two sisters and one unrelated patient). Relevant articles were searched by using the term "HSD17B3" OR "17beta-HSD3 gene" with restrictions on language (English) and species (human) in Pubmed and Embase. All the three phenotypically female subjects showed 46, XY karyotype, inguinal masses, decreased testosterone and increased androstenedione. Two novel homozygous mutations (W284X and c.124_127delTCTT) in HSD17B3 gene were identified. A systematic review found a total of 121 pedigrees/158 patients, with 78.5% (124/158) of patients assigned as females, 15.2% (24/158) from females to males, and 5.1% (8/158) raised as males. The most common mutation was c.277+4C>T (allele frequency: 25/72) for patients from Europe, and R80Q (allele frequency: 21/54) for patients from West Asia. The testicular histology showed normal infantile testicular tissue in 100% (9/9) infantile patients, normal quantity germ cells in 44.4% (8/18) prepubertal patients and 19.0% (4/21) pubertal and adult patients. We reported the first East Asian 17β-hydroxysteroid dehydrogenase 3 deficiency cases. Additional literature reviews found founder effects among patients with different ethnic background and early orchiopexy may benefit fertility in patients assigned as males. These findings may significantly expand the clinical, ethnic and genetic spectrum of 17β-hydroxysteroid dehydrogenase 3 deficiency.
17β-羟类固醇脱氢酶3缺乏症是一种由HSD17B3基因突变导致的46, XY性发育障碍的罕见常染色体隐性病因，然而，东亚地区尚无病例报道。本研究旨在报告单中心3例患有17β-HSD3缺乏症的中国46, XY女性患者，并对相关文献进行系统综述。对3例表型为女性的中国患者（2例姐妹和1例非亲属患者）进行了临床检查、内分泌评估及HSD17B3基因测序。在PubMed和Embase数据库中使用检索词“HSD17B3”或“17β-HSD3基因”，并限定语言为英语、物种为人类，检索相关文章。所有3例表型为女性的受试者均显示46, XY核型、腹股沟肿块、睾酮降低及雄烯二酮升高。在HSD17B3基因中鉴定出2个新的纯合突变（W284X和c.124_127delTCTT）。系统综述发现共有121个家系/158例患者，其中78.5%（124/158）的患者被判定为女性，15.2%（24/158）的患者从女性转变为男性，5.1%（8/158）的患者被当作男性抚养。欧洲患者最常见的突变是c.277 + 4C>T（等位基因频率：25/72），西亚患者最常见的突变是R80Q（等位基因频率：21/54）。睾丸组织学检查显示，100%（9/9）的婴幼儿患者睾丸组织为正常婴幼儿期表现，44.4%（8/18）的青春期前患者生殖细胞数量正常，19.0%（4/21）的青春期及成年患者生殖细胞数量正常。我们报告了首例东亚地区17β-羟类固醇脱氢酶3缺乏症病例。进一步的文献综述发现不同种族背景患者中存在奠基者效应，早期睾丸固定术可能对判定为男性的患者生育有益。这些发现可能会显著拓宽17β-羟类固醇脱氢酶3缺乏症的临床、种族及基因谱。
