Supplementary Material for: Phenotypic Variation in 46,XX Disorders of Sex Development due to the 4th Zinc Finger Domain Variant of WT1 : A Familial Case Report

Introduction: The variants in the zinc finger (ZF) domains 1–3 in WT1 are one of the major causes of 46,XY disorders of sex development. Recently, the variants in fourth ZF (ZF4 variants) were reported to cause 46,XX DSD. However, all the nine patients reported were de novo, and no familial cases were identified. Case presentation and Results: The proband (16yrs social female), had 46,XX karyotype with dysplastic testes and moderate virilization in genitalia. A ZF4 variant, p.Arg495Gln in WT1 was identified in the proband, her brother and mother. The mother did not show any virilization with normal fertility, and the 46,XY brother developed normal puberty. Discussion/Conclusion: The phenotypic variations due to ZF4 variant are extremely broad in 46,XX cases.

引言：WT1基因第1至3号锌指（zinc finger, ZF）结构域的变异是引发46,XY性发育障碍（disorders of sex development, DSD）的主要病因之一。近期有研究指出，第4号锌指结构域变异（ZF4变异）可导致46,XX DSD，但目前已报道的9例患者均为新发变异，尚未发现家族性病例。

病例报告与结果：本研究的先证者为16岁社会性别女性，核型为46,XX，伴有发育不良睾丸及生殖器中度男性化表现。研究在该先证者、其兄长与母亲体内均检测到WT1基因的ZF4变异：p.Arg495Gln。其母亲无任何男性化症状且生育功能正常，核型为46,XY的兄长青春期发育完全正常。

讨论与结论：ZF4变异所致的表型差异在46,XX病例中跨度极大。