• PMID: 22907560
• Gene Name: NR5A1
• Condition: Infertility
• Association: The study confirms that reserved fertility can be observed in patients with a 46,XY disorder of sex development due to heterozygous mutations in the NR5A1 gene
• Mutation: c.938G?A->p.Arg313His
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Gonadal dysgenesis

Preserved fertility in a patient with a 46,XY disorder of sex development due to a new heterozygous mutation in the NR5A1/SF-1 gene: evidence of 46,XY and 46,XX gonadal dysgenesis phenotype variability in multiple members of an affected kindred

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

In humans, steroidogenic factor 1 (NR5A1/SF-1) mutations have been reported to cause gonadal dysgenesis, with or without adrenal failure, in both 46,XY and 46,XX individuals. We have previously reported extreme within-family variability in affected 46,XY patients. Even though low ovarian reserve with preserved fertility has been reported in females harboring NR5A1 gene mutations, fertility has only been observed in one reported case in affected 46,XY individuals. A kindred with multiple affected members presenting gonadal dysgenesis was studied. Four 46,XY individuals presented severe hypospadias at birth, one of them associated with micropenis and cryptorchidism. The other 3 developed spontaneous male puberty, and 1 has fathered 5 children. Four 46,XX patients presented premature ovarian failure (one of them was not available for the study) or high follicle-stimulating hormone levels. Mutational analysis of the NR5A1 gene revealed a novel heterozygous mutation, c.938G→A, predicted to cause a p.Arg313Hys amino acid change. A highly conserved amino acid of the ligand-binding domain of the mature protein is affected, predicting abnormal protein function. We confirm that preserved fertility can be observed in patients with a 46,XY disorder of sex development due to heterozygous mutations in the NR5A1 gene. CI - Copyright © 2012 S. Karger AG, Basel. FAU - Ciaccio, Marta AU - Ciaccio M AD - Endocrinology Service, Hospital de Pediatría Garrahan, Buenos Aires, Argentina. FAU - Costanzo, Mariana AU - Costanzo M FAU - Guercio, Gabriela AU - Guercio G FAU - De Dona, Valeria AU - De Dona V FAU - Marino, Roxana AU - Marino R FAU - Ramirez, Pablo C AU - Ramirez PC FAU - Galeano, Jessica AU - Galeano J FAU - Warman, Diana Monica AU - Warman DM FAU - Berensztein, Esperanza AU - Berensztein E FAU - Saraco, Nora AU - Saraco N FAU - Baquedano, Maria Sonia AU - Baquedano MS FAU - Chaler, Eduardo AU - Chaler E FAU - Maceiras, Mercedes AU - Maceiras M FAU - Lazzatti, Juan Manuel AU - Lazzatti JM FAU - Rivarola, Marco A AU - Rivarola MA