Title :

NOBOX gene variants in premature ovarian insufficiency: ethnicity-dependent insights.

Author(s) :

Jordan, P. [Auteur]
Verebi, C. [Auteur]
Perol, S. [Auteur]
Grotto, S. [Auteur]
Fouveaut, C. [Auteur]
Christin-Maitre, S. [Auteur]
De La Perrière, A. B. [Auteur]
Grouthier, V. [Auteur]
Jonard-Catteau, Sophie [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Touraine, P. [Auteur]
Plu-Bureau, G. [Auteur]
Dupont, J. M. [Auteur]
El Khattabi, L. [Auteur]
Bienvenu, Thierry [Auteur]
Hôpital Cochin [AP-HP]

Journal title :

Journal of Assisted Reproduction and Genetics

Abbreviated title :

J Assist Reprod Genet

Volume number :

41

Pages :

135–146

Publisher :

Springer Link

Publication date :

2023-11-08

ISSN :

1573-7330

English keyword(s) :

NOBOX
Premature ovarian insufficiency
Penetrance

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Purpose 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 ...
Show more >Purpose 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. Methods 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. Results 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. Conclusion 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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Submission date :

2024-05-15T21:50:50Z
2024-09-18T07:45:28Z