The diagnostic value of whole exome sequencing in non-obstructive azoospermia patients

Janis Kristaps Vasilonoks, Elvita Penka, Baiba Alkšere (Scientific Advisor), Agrita Puzuka (Scientific Advisor), Aigars Dzalbs (Scientific Advisor), Violeta Fodina (Scientific Advisor), Juris Ērenpreiss (Scientific Advisor), Baiba Vilne (Scientific Advisor)

Research output: Contribution to conferencePosterpeer-review


Objectives. The purpose of this study was to investigate the potential of exome sequencing
in idiopathic azoospermia cases. Male infertility is a multifactorial pathology with genetic
causes suggested as the underlying factors in majority of cases of severe male infertility. Nonobstructive azoospermia (NOA) is a disorder that leads to infertility in men. Various genetic
variants have been discovered as causes of NOA. The recent emergence of next generation
sequencing (NGS) offers an opportunity to analyze many genes at once. There is still a lack of
reports on WES implementation in routine clinical diagnostics.
Materials and methods. Whole exome sequencing was performed on 17 non-obstructive
azoospermia patients. A gene set of interest was compiled. Samples were sequenced using the
Twist Comprehensive Exome Panel. The resulting sequences were mapped against the human
genome GRCh38 reference sequence using BWAMEM. Copy number variations (CNV) were
annotated using AnnotSV. Samples were analyzed and filtered with the Illumina’s BaseSpace
Variant Interpreter. Variants considered as pathogenic and likely pathogenic were confirmed
by Sanger sequencing.
Results. We detected four genetic variants of unknown significance (VUS) in genes,
affecting the hypothalamic–pituitary–gonadal axis - NR5A1, FGFR1, GNRHR and
KISS1R. Clinical investigation did not demonstrate hypogonadism in the subject group.
NM_004959(NR5A1):c.763C>T was interpreted at first as likely pathogenic (LP), according
to ACMG guidelines. The patient’s phenotype did not reflect the expected phenotype. This
genetic variant was considered as a variant of unknown significance (VUS). No previously
described known pathogenic genetic variants were identified.
Conclusions. We identified four genetic variants in WES, based on a preselected diagnostic
gene panel. These findings can add supporting information to the knowledge base of infertility
diagnostics WES as a routine diagnostics method in azoospermia investigation remains
questionable. Genetic counselling for idiopathic azoospermia patients should be considered
to ensure appropriate investigation of possible inherited infertility causes.

Field of Science*

  • 3.1 Basic medicine
  • 3.2 Clinical medicine

Publication Type*

  • 3.4. Other publications in conference proceedings (including local)


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