engleski

Genetic analysis of azoospermic men by an integrated NGS panel

Introduction: Y chromosome microdeletions, Klinefelter syndrome and CFTR mutations are the leading genetic causes of azoospermia and are all analyzed by different molecular methods. In addition, a number of candidate genes were related to infertility in the last two decades. Materials/Methods: We designed an NGS amplicon- based panel that simultaneously analyzes all the known above-mentioned genetic variants as well as 11 additional genes recently being associated with azoospermia and ran the analysis on 44 azoospermic men. Twelve samples with known genetic aetiology were used to evaluate the performance of the NGS amplicon-based test. Remaining thirty-two samples consisted of azoospermic men with no defined cause of infertility. The panel consisted of 393 amplicons covering regions of interest. In house bioinformatic pipeline was developed to analyse the raw data. Results: We correctly detected all genetic variants in men with known genetic aetiology. In 32 samples with no defined cause of infertility, we detected three Y chromosome microdeletions and 6 variants in selected genes that passed our filtering criteria for functional impact (in CFTR, SYCE1L, TEX15 and AR). Altogether, we detected a genetic cause of azoospermia in 4 individuals and likely causative variants in another 4 out of 32 individuals by running our NGS amplicon-based panel. Conclusions: This work showed that genetic variants associated with male infertility could be detected by running only one assay. Moreover, customization of the panel with newly discovered genes increases the chance of finding the genetic cause of male patient infertility.

azoospermia ; genetic analysis

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