Supplementary Material for: A Hemizygous MED12 Variant in Three Brothers with Hypomasculinized Genitalia and Additional Clinical Features: A Case Report

Introduction: MED12 is a causative gene for congenital malformation syndromes. The association between MED12 variants 46,XY disorders/differences of sex development (DSD) remains unclear, although several variant-positive patients exhibited genital abnormalities. Case presentation: Three siblings manifested hypomasculinized genitalia, including hypospadias and cryptorchidism, with normal or mildly increased gonadotropin levels. Two patients showed normal spontaneous puberty. Whole exome sequencing identified a maternally-derived hemizygous MED12 variant (c.3064A>G, p.Met1022Val). One patient lacked typical clinical features of MED12-associated malformation syndromes. Conclusion: MED12 variants may be associated with 46,XY DSD with or without congenital malformation syndromes through testicular dysfunction and defective genital formation during fetal development.