Krishnappa Brijesh, Arya Sneha, Lila Anurag R, Sarathi Vijaya, Memon Saba S, Barnabas Rohit, Kumbhar Bajarang V, Bhandare Vishwambhar V, Patil Virendra, Shah Nalini S, Kunwar Ambarish, Bandgar Tushar
Department of Endocrinology, Seth G S Medical College & KEM Hospital, Mumbai, Maharashtra, India.
Department of Endocrinology, Vydehi Institute of Medical Sciences and Research Centre, Bangalore, Karnataka, India.
Clin Endocrinol (Oxf). 2022 Jul;97(1):43-51. doi: 10.1111/cen.14694. Epub 2022 Feb 27.
To describe Asian Indian patients with 17β hydroxysteroid dehydrogenase 3 (17βHSD3) deficiency and to perform a systematic review to determine the factors influencing gender role in 46,XY disorder of sex development (DSD) due to 17βHSD3 deficiency.
We present the phenotypic and genotypic data of 10 patients (9 probands and 1 affected family member) with 17βHSD3 deficiency from our 46,XY DSD cohort (N = 150; Western India) and a systematic review of 152 probands with genetically proven, index 17βHSD3 deficiency patients from the world literature to identify the determinants of gender role.
17βHSD3 deficiency was the third most common (6%) cause of non-dysgenetic 46,XY DSD in our cohort. Five patients each had prepubertal (atypical genitalia) and pubertal (primary amenorrhoea) presentations. Six patients were initially reared as female of whom two (one each in prepubertal and pubertal age) changed their gender role. Ten pathogenic molecular variants (six novel) were observed. In the systematic review, initial male sex of rearing was uncommon (10.5%) and was associated with atypical genitalia, higher testosterone/androstenedione (T/A) ratio and Asian origin. Gender role change to male was seen in 10.3% of patients with initial female sex of rearing and was associated with Asian origin but unrelated to pubertal androgens or molecular variant severity. It has not been reported in patients of European origin.
We report the first Indian case series of 17βHSD3 deficiency, the third most common cause of 46,XY DSD, with six novel molecular variants. Distinct geographical differences in the frequency of initial male sex of rearing and gender role change to male in those initially reared as females in 17βHSD3 deficiency were noted which needs further evaluation for the underlying molecular mechanisms.
描述患有17β羟类固醇脱氢酶3（17βHSD3）缺乏症的亚洲印度患者，并进行系统综述，以确定影响因17βHSD3缺乏导致的46，XY性发育障碍（DSD）中性别角色的因素。
我们展示了来自我们46，XY DSD队列（N = 150；印度西部）的10例17βHSD3缺乏症患者（9例先证者和1名受影响家庭成员）的表型和基因型数据，并对世界文献中152例经基因证实的17βHSD3缺乏症索引患者进行了系统综述，以确定性别角色的决定因素。
在我们的队列中，17βHSD3缺乏症是46，XY非发育异常性DSD的第三大常见病因（6%）。五例患者分别有青春期前（生殖器异常）和青春期（原发性闭经）表现。六例患者最初被抚养为女性，其中两例（青春期前和青春期各一例）改变了性别角色。观察到10种致病分子变异（6种为新发现）。在系统综述中，最初抚养为男性的情况不常见（10.5%），且与生殖器异常、较高的睾酮/雄烯二酮（T/A）比值及亚洲血统有关。最初抚养为女性的患者中有10.3%的人性别角色转变为男性，这与亚洲血统有关，但与青春期雄激素或分子变异严重程度无关。欧洲血统患者中未见此情况报道。
我们报告了首个印度17βHSD3缺乏症病例系列，这是46，XY DSD的第三大常见病因，有6种新的分子变异。注意到17βHSD3缺乏症患者中，最初抚养为男性的频率以及最初抚养为女性者性别角色转变为男性的频率存在明显的地理差异，这需要对潜在分子机制进行进一步评估。
