Preserved fertility in a patient with a 46,XY disorder of sex development (DSD) due to a new heterozygous mutation in the NR5A1/SF-1 gene. Evidences of 46,XY and 46,XX gonadal dysgenesis phenotype variability in multiple members of the affected offspring

CIACCIO, M; COSTANZO, M; GUERCIO, G; DE DONA, V; MARINO, R; RAMIREZ, P; GALEANO, J; WARMAN, M; BERENSZTEIN, E; SARACCO, N; BAQUEDANO MARÍA SONIA; CHALER, E; MACEIRAS, M; LAZZATI, J; RIVAROLA, M; BELGOROSKY, A

Hormone Research in Paediatrics

KARGER

Lugar: Basel; Año: 2012 vol. 75 p. 70 - 77

1663-2818

  Background: In humans, steroidogenic factor 1 (NR5A/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 46,XY affected patients. Even though low ovarian reserve with preserved fertility has been reported in females harboring NR5A1 gene mutations, fertility has been only observed in one reported case in 46,XY affected individuals. Case Reports: 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 three developed spontaneous male puberty, one has fathered five children. Four 46,XX patients presented premature ovarian failure (one of them was not available for the study), or high FSH 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 aminoacid of the ligand-binding domain of the mature protein is affected, predicting an abnormal protein function Conclusion: We confirm that preserved fertility can be observed in patients with a 46, XY DSD due to heterozygous mutations in the NR5A1 gene.