A novel functional variant in Wilms' Tumor 1 (WT1) is associated with idiopathic non-obstructive azoospermia.
Mol Reprod Dev
; 84(3): 222-228, 2017 03.
Article
en En
| MEDLINE
| ID: mdl-27990711
ABSTRACT
Idiopathic nonobstructive azoospermia (INOA) is one of the most severe forms of male infertility, yet its pathophysiology remains unclear. WT1 (Wilms' tumor 1) regulates the polarity of Sertoli cells, thereby playing a critical, indirect role in spermatogenesis. Here, we evaluated WT1 gene variation associates with INOA by assessing its promoter and coding regions in 200 patients diagnosed with INOA and 200 proven-fertile men. Three novel variants in the WT1 coding region were detected only in INOA patients, including two synonymous variants and one missense variant, p.Phe435Leu (p.F435L), which was predicted to be deleterious to protein function. The results of dual luciferase reporter showed that the WT1 p.F435L variant decreases transcription of COL4A1 and WNT4 promoters through a dominant-negative effect. Furthermore, chromatin immunoprecipitation assays revealed that COL4A1 and WNT4 promoter is directly bound by wild-type WT1 protein, but not the p.F435L WT1 variant. Thus, we identified a novel functional variant of WT1 functionally associated with INOA. Mol. Reprod. Dev. 84 222-228, 2017. © 2017 Wiley Periodicals, Inc.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Mutación Missense
/
Proteínas WT1
/
Azoospermia
Tipo de estudio:
Risk_factors_studies
Límite:
Adult
/
Humans
/
Male
Idioma:
En
Revista:
Mol Reprod Dev
Asunto de la revista:
BIOLOGIA MOLECULAR
/
MEDICINA REPRODUTIVA
Año:
2017
Tipo del documento:
Article
País de afiliación:
China