NOBOX gene variants in premature ovarian insufficiency: ethnicity-dependent insights.
NOBOX
Penetrance
Premature ovarian insufficiency
Journal
Journal of assisted reproduction and genetics
ISSN: 1573-7330
Titre abrégé: J Assist Reprod Genet
Pays: Netherlands
ID NLM: 9206495
Informations de publication
Date de publication:
03 Nov 2023
03 Nov 2023
Historique:
received:
03
08
2023
accepted:
20
10
2023
medline:
3
11
2023
pubmed:
3
11
2023
entrez:
3
11
2023
Statut:
aheadofprint
Résumé
Premature ovarian insufficiency (POI) affects approximately 1% of women before the age of 40. Genetic contribution is a significant component of POI. The NOBOX gene was considered one of the major genetic causes of POI. However, the pathogenicity and the penetrance of NOBOX variants remain unclear. We studied the whole coding region of the NOBOX gene by next generation sequencing in a cohort of 810 patients with POI, and we compared the frequency of each identified NOBOX variant to the general population taking into account the ethnicity of each individual. Screening of the whole coding region of the NOBOX gene allowed us to identify 35 different variants, including 5 loss-of-function variants. In total, 171 patients with POI (25%) carried out at least one NOBOX variant. Regarding missense variants, we observed a significant overrepresentation of the most frequent ones in our 810 POI patients as compared to the general, except for p.(Arg117Trp). However, taking into account the ethnic origin of the individuals, we observed no significant OR difference for p.(Arg44Leu) and p.(Arg117Trp) in African subgroup and for p.(Asp452Asn) in European subgroup. This population study suggests that the p.(Arg44Leu) variant could be considered benign variant and that the p.(Asp452Asn) and p.(Arg117Trp) variants could be considered moderate risk pathogenic variants with probably partial and very low penetrance and/or expressivity. In contrast, p.(Gly91Trp) and p.(Gly152Arg) variants could be considered pathogenic variants with a moderate functional impact.
Identifiants
pubmed: 37921973
doi: 10.1007/s10815-023-02981-y
pii: 10.1007/s10815-023-02981-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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