ClinVar

In a 46,XY patient showing gonadal dysgenesis with normal adrenal function (SRXY3; 612965), Mallet et al. (2004) reported a heterozygous SF1 gene mutation, a C-to-A transversion in exon 2 that replaced cys16 with a stop codon (C16X). The patient showed low basal levels of anti-mullerian hormone (600957) and testosterone (T), weak T response to chorionic gonadotropin (see 118860), and hypoplastic testes with abundant seminiferous tubules but rare germ cells. This mutation caused premature termination of translation and should abolish all SF1 activity; therefore, haploinsufficiency could explain the deleterious effect of this mutation, suggesting that testis development is more SF1 dose-dependent than adrenal development. The authors concluded that heterozygous mutation can impair adrenal development only if the 2 mechanisms, gene dosage and dominant-negative effects, occur.