ClinVar

Hasegawa et al. (2004) identified an SF1 mutation in a 27-year-old Japanese patient with a 46,XY karyotype and complete gonadal dysgenesis (SRXY3; 612965). Sequence analysis of all 7 exons of SF1 revealed a heterozygous 1-bp deletion at exon 2, 18delC, that was predicted to cause a frameshift at codon 6 and result in termination at codon 74 (Asp6fsTer74). Western blot analysis demonstrated no evidence of an amino-truncated SF1 protein despite the 18delC mutation being very close to the natural translation start codon. Transcription analysis indicated that the mutant was transcriptionally inactive and had no dominant-negative effect. Clinical features included small dysgenetic testes with vasa deferentia and epididymides, absent uterus, blind-ending vagina, and clitoromegaly. The authors concluded that SF1 haploinsufficiency can selectively impair testicular development and permit the biosynthesis of AMH (600957) and testosterone in dysgenetic testes and the production of gonadotropins in pituitary gonadotropes.