Should TSPYL1 mutation screening be included in routine diagnostics of male idiopathic infertility?

Objective: To investigate a putative role of TSPYL1 in male idiopathic infertility.

Design: Clinical article.

Setting: University hospital.

Patient(s): A total of 104 infertile men were selected with idiopathic nonobstructive azoospermia, cryptozoospermia, oligozoospermia, oligonecrozoospermia, and oligoasthenoteratozoospermia (OAT) syndrome, along with a control group of 106 men with proven paternity.

Intervention(s): Mutation screening of the coding region and parts of the 5' and 3' untranslated regions of the TSPYL1 gene was performed by polymerase chain reaction and sequencing.

Main Outcome Measure(s): Occurrence of TSPYL1 single-nucleotide polymorphisms (SNPs) and mutations.

Result(s): In these cohorts, eight known TSPYL1 SNPs were identified, none of which was significantly associated with male infertility. Two potentially disease-causing variants were detected in the infertile cohort: one man with azoospermia was found to be heterozygous for the novel TSPYL1 variant c.419C>G (p.Ser140Cys), and the rare substitution c.1098C>A (p.Phe366Leu) was identified in a man with OAT syndrome in the heterozygous state. Additionally, one fertile man was found to be heterozygous for the rare variant c.487G>A (p.Val163Ile). In silico analyses predicted a nonpathogenic effect for all amino acid exchanges, although protein features might be affected by p.Ser140Cys and p.Phe366Leu, respectively.

Conclusion(s): Mutations in the TSPYL1 gene do not seem to play a major role in the pathogenesis of idiopathic male infertility, and mutation screening of the TSPYL1 gene can currently not be recommended in routine diagnostics of idiopathic male infertility.