Back to Search
Start Over
Association of ESX1 gene variants with non-obstructive azoospermia in Chinese males
- Source :
- Scientific Reports, Scientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Genetic factors are one of the most important causes of non-obstructive azoospermia (NOA). ESX1 is an X-linked testis-biased expressed gene, and a potential biomarker for testicular sperm retrieval in NOA patients, yet few systematic studies have investigated its association with NOA. Here, we performed selected exonic sequencing in a large cohort of Chinese males, and four novel missense mutations (including one compound mutation), one novel synonymous mutation of ESX1 unique to NOA patients were identified. We analyzed the effects of ESX1 mutations on cyclin A degradation and cell cycle progression by immunoprecipitation assay and flow cytometry, and found that the compound mutant p.[P365R; L366V] ESX1 compromised the stabilizing effect of ESX1 on polyubiquitinated cyclin A, thereby causing the failure of M phase arrest in cells. Further studies showed that the deleterious effect of the compound mutations on ESX1 protein function was attributed to p.P365R but not p.L366V alteration. The novel ESX1 mutation p.P365R might confer high risk for NOA in Han Chinese population, probably via affecting cell cycle control.
- Subjects :
- Male
0301 basic medicine
Silent mutation
China
Reproductive disorders
Science
Mutant
Cyclin A
Mutation, Missense
Biology
medicine.disease_cause
Article
03 medical and health sciences
0302 clinical medicine
Testis
Gene expression
medicine
Humans
Missense mutation
Gene
Azoospermia
Homeodomain Proteins
Genetics
Mutation
030219 obstetrics & reproductive medicine
Multidisciplinary
Cell Cycle
medicine.disease
Urogenital diseases
030104 developmental biology
biology.protein
Medicine
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....d49c6cc01ba61e1a8d68be02d575ca27