FGF9 variant in 46,XY DSD patient suggests a role for dimerization in sex determination.
DSD
FGF9
sex determination
sex reversal
synostosis
testis
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
revised:
28
10
2022
received:
02
09
2022
accepted:
28
10
2022
pubmed:
10
11
2022
medline:
4
2
2023
entrez:
9
11
2022
Statut:
ppublish
Résumé
46,XY gonadal dysgenesis (GD) is a Disorder/Difference of Sex Development (DSD) that can present with phenotypes ranging from ambiguous genitalia to complete male-to-female sex reversal. Around 50% of 46,XY DSD cases receive a molecular diagnosis. In mice, Fibroblast growth factor 9 (FGF9) is an important component of the male sex-determining pathway. Two FGF9 variants reported to date disrupt testis development in mice, but not in humans. Here, we describe a female patient with 46,XY GD harbouring the rare FGF9 variant (missense mutation), NM_002010.2:c.583G > A;p.(Asp195Asn) (D195N). By biochemical and cell-based approaches, the D195N variant disrupts FGF9 protein homodimerisation and FGF9-heparin-binding, and reduces both Sertoli cell proliferation and Wnt4 repression. XY Fgf9
Substances chimiques
Fibroblast Growth Factor 9
0
FGF9 protein, human
0
Fgf9 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
277-287Informations de copyright
© 2022 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.
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