Genetic dissection of spermatogenic arrest through exome analysis: clinical implications for the management of azoospermic men.

ABSTRACT:

Purpose

Azoospermia affects 1% of men and it can be the consequence of spermatogenic maturation arrest (MA). Although the etiology of MA is likely to be of genetic origin, only 13 genes have been reported as recurrent potential causes of MA.

Methods

Exome sequencing in 147 selected MA patients (discovery cohort and two validation cohorts).

Results

We found strong evidence for five novel genes likely responsible for MA (ADAD2, TERB1, SHOC1, MSH4, and RAD21L1), for which mouse knockout (KO) models are concordant with the human phenotype. Four of them were validated in the two independent MA cohorts. In addition, nine patients carried pathogenic variants in seven previously reported genes-TEX14, DMRT1, TEX11, SYCE1, MEIOB, MEI1, and STAG3-allowing to upgrade the clinical

SUBMITTER: Krausz C 

PROVIDER: S-EPMC7710580 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature