title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Endocrinology Service, Hospital de Pediatria Garrahan, Buenos Aires, Argentina.
authors.forename: Diana Monica
authors.initials: DM
authors.lastname: Warman
authors.forename: Mariana
authors.initials: M
authors.lastname: Costanzo
authors.forename: Roxana
authors.initials: R
authors.lastname: Marino
authors.forename: Esperanza
authors.initials: E
authors.lastname: Berensztein
authors.forename: Jesica
authors.initials: J
authors.lastname: Galeano
authors.forename: Pablo C
authors.initials: PC
authors.lastname: Ramirez
authors.forename: Nora
authors.initials: N
authors.lastname: Saraco
authors.forename: Maria Sonia
authors.initials: MS
authors.lastname: Baquedano
authors.forename: Marta
authors.initials: M
authors.lastname: Ciaccio
authors.forename: Gabriela
authors.initials: G
authors.lastname: Guercio
authors.forename: Eduardo
authors.initials: E
authors.lastname: Chaler
authors.forename: Mercedes
authors.initials: M
authors.lastname: Maceiras
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Lazzatti
authors.forename: Marcela
authors.initials: M
authors.lastname: Bailez
authors.forename: Marco A
authors.initials: MA
authors.lastname: Rivarola
authors.forename: Alicia
authors.initials: A
authors.lastname: Belgorosky
mesh_terms: D058489:46, XX Disorders of Sex Development / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D058490:Disorder of Sex Development, 46,XY / Q000235:genetics* / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D006059:Gonadal Dysgenesis / Q000235:genetics; D006801:Humans; D006965:Hyperplasia; D007021:Hypospadias / Q000235:genetics; D007223:Infant; D008297:Male; D009154:Mutation; D010375:Pedigree; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D054339:Steroidogenic Factor 1 / Q000235:genetics*; D013737:Testis / Q000473:pathology; D055815:Young Adult
chemical_list: C515057:NR5A1 protein, human; D054339:Steroidogenic Factor 1