A case report of premature ovarian insufficiency caused by a novel FANCL mutation(c.1033G>A)and in vitro functional validation
10.3969/j.issn.1672-8467.2025.02.014
- VernacularTitle:FANCL新突变(c.1033G>A)致早发性卵巢功能不全1例报道及体外功能验证
- Author:
Yi-qing LIU
1
;
Shu-ting REN
;
Yun-cheng PAN
;
Feng ZHANG
;
Xiao-jin ZHANG
;
Yan-hua WU
Author Information
1. 复旦大学生命科学学院遗传学系 上海 200433
- Publication Type:Journal Article
- Keywords:
premature ovarian insufficiency(POI);
FANCL;
whole exome sequencing(WES);
missense mutation;
protein stability
- From:
Fudan University Journal of Medical Sciences
2025;52(2):270-276,291
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the characteristics of a novel FANCL mutation identified in a patient with premature ovarian insufficiency(POI)and to explore its potential functional impacts in vitro.Methods A novel FANCL heterozygous mutation c.1033G>A(p.Glu345Lys)was screened in a patient with POI using whole exome sequencing(WES),which was found to be inherited from a mother who had undergone early menopause.The authenticity of the mutation was identified by Sanger sequencing and the conserved nature of the mutation site was predicted by software.Overexpressing FANCL mutant and wildtype plasmids were constructed and transiently transfected into HEK293T cell lines,and the effect of the mutation was detected by qPCR,immunofluorescence and Western blot.Results The mutation site of FANCL was located within the Ring domain of FANCL,which was highly conserved across multiple species.The mutant showed no significant change in mRNA expression level,while the protein expression level was significantly down-regulated.In vitro cellular experiments further revealed that the mutation leads to decreased expression levels by reducing protein stability.Conclusion A FANCL c.1033G>A mutation was found and it may cause disease in the POI patient due to decreased protein stability.
