• PMID: 20861607
• Gene Name: NR5A1
• Condition: 46,XY disorders of sex development (DSD), 46,XX ovarian insufficiency
• Association: Family 1 had 2 affected 46,XY DSD subjects. One, born with severe perineal hypospadias, was raised as a male, and presented normal adolescence. The other, born with ambiguous genitalia, uterus, and mild testicular dysgenesis, was raised as a female. A W27
• Mutation: W279X, intronic deletion (g3314-3317delTCTC (IVS 4 + 8), Y183X
• Population size: 6
• Population details: 7 (6 46,XY DSD or hypospadias, 1 46,XX ovarian insufficiency)
• Sex: Male, female
• Infertility type: Male infertility, Female infertility
• Other associated phenotypes: 46,XY disorders of sex development (DSD), 46,XX ovarian insufficiency

Three new SF-1 (NR5A1) gene mutations in two unrelated families with multiple affected members: within-family variability in 46,XY subjects and low ovarian reserve in fertile 46,XX subjects

Warman DM, Costanzo M, Marino R, Berensztein E, Galeano J, Ramirez PC, Saraco N, Baquedano MS, Ciaccio M, Guercio G, Chaler E, Maceiras M, Lazzatti JM, Bailez M, Rivarola MA, Belgorosky A.

BACKGROUND: Three novel heterozygous SF-1 gene mutations affecting multiple members of two unrelated families with a history of 46,XY disorders of sex development (DSD) and 46,XX ovarian insufficiency are described. METHODS: clinical and mutational analysis of the SF-1 gene in 9 subjects of two families. RESULTS: family 1 had 2 affected 46,XY DSD subjects. One, born with severe perineal hypospadias, was raised as a male, and presented normal adolescence. The other, born with ambiguous genitalia, uterus, and mild testicular dysgenesis, was raised as a female. A W279X heterozygous mutation and an intronic deletion (g3314-3317delTCTC (IVS 4 + 8) was found in the SF-1 gene. In family 2, 4/6 affected siblings had 46,XY DSD or hypospadias. An affected 46,XX sister had normal sexual development but increased FSH levels. The 37-year-old affected mother had entered menopause. An Y183X heterozygous mutation was detected. CONCLUSION: an extreme within-family phenotypic variability, ranging from severe prenatal undervirilization to normal pubertal development, was observed in 46,XY-affected siblings, indicating that other unknown factors might be involved in the phenotype. Low ovarian reserve and preserved fertility in 46,XX subjects can be observed in heterozygous SF-1 gene mutations. CI - 2010 S. Karger AG, Basel. FAU - Warman, Diana Monica AU - Warman DM AD - Endocrinology Service, Hospital de Pediatria Garrahan, Buenos Aires, Argentina. FAU - Costanzo, Mariana AU - Costanzo M FAU - Marino, Roxana AU - Marino R FAU - Berensztein, Esperanza AU - Berensztein E FAU - Galeano, Jesica AU - Galeano J FAU - Ramirez, Pablo C AU - Ramirez PC FAU - Saraco, Nora AU - Saraco N FAU - Baquedano, Maria Sonia AU - Baquedano MS FAU - Ciaccio, Marta AU - Ciaccio M FAU - Guercio, Gabriela AU - Guercio G FAU - Chaler, Eduardo AU - Chaler E FAU - Maceiras, Mercedes AU - Maceiras M FAU - Lazzatti, Juan Manuel AU - Lazzatti JM FAU - Bailez, Marcela AU - Bailez M FAU - Rivarola, Marco A AU - Rivarola MA