• PMID: 21214500
• Gene Name: HSD17B3
• Condition: 46,XY disorders of sex development, mild clitoral hypertrophy
• Association: A low T/?4 ratio is indicative of 17?HSD-3 deficiency and associated with isolated clitoromegaly. The R80 site is critical for NADPH binding, thus the mutation at this site leads to 17?HSD-3 deficiency presenting as 46,XY disorder of sex development.
• Mutation: R80W
• Population size: 1
• Population details: 1 46,XY disorder of sex development
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: 46,XY disorders of sex development, mild clitoral hypertrophy

Isolated mild clitoral hypertrophy may reveal 46,XY disorders of sex development in infancy due to 17?HSD-3 defect confirmed by molecular analysis

George MM, Sinha S, Mamkin I, Philibert P, New MI, Wilson RC, Sultan C, Ten S, Bhangoo A.

AIMS: 17-β-Hydroxysteroid dehydrogenase type 3 (17βHSD-3) is expressed exclusively in the testes where it converts Δ4 androstenedione (Δ4) to testosterone (T). Here, we report a patient with a rare mutation at a critical site in HSD17B3 gene leading to deficiency of 17β HSD-3 enzyme. METHODS: We describe a 3-year old healthy female of consanguineous Lebanese descent, who presented to the endocrine service with isolated mild clitoromegaly. Adrenocorticotropic hormone (ACTH) and human chorionic gonadotrophin (hCG) stimulation tests were performed. Genes for sex-determining region Y (SRY), steroidogenic factor-1 (SF-1) and 17βHSD-3 (HSD17B3) were sequenced. RESULTS: The post-hCG stimulation T levels and T/Δ4 ratio was low. Patient had a 46,XY karyotype. Sequence analysis of the HSD17B3 gene revealed a homozygous R80W missense mutation on exon 3. No mutation was found in SRY and SF1 genes. Mullerian structures were not detected on pelvic imaging. CONCLUSIONS: A low T/Δ4 ratio is indicative of 17βHSD-3 deficiency and associated with isolated clitoromegaly. The R80 site is critical for NADPH binding, thus the mutation at this site leads to 17βHSD-3 deficiency presenting as 46,XY disorder of sex development. FAU - George, Minu M AU - George MM AD - Pediatric Endocrinology Division, Maimonides Infants and Children's Hospital and Children's Hospital at SUNY Downstate, Brooklyn, NY, USA. FAU - Sinha, Sunil AU - Sinha S FAU - Mamkin, Irene AU - Mamkin I FAU - Philibert, Pascal AU - Philibert P FAU - New, Maria I AU - New MI FAU - Wilson, Robert C AU - Wilson RC FAU - Sultan, Charles AU - Sultan C FAU - Ten, Svetlana AU - Ten S