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

TSPYL1 variants are not clearly associated with idiopathic male infertility. Mutation screening of the TSPYL1 gene can currently not be recommended in diagnostics of idiopathic male infertility.


Poupak Javaher, M.D., M.P.H., Manfred Stuhrmann, M.D., Christina Wilke, B.Sc., Eileen Frenzel, M.Sc., Georgi Manukjan, M.Sc., Anika Grosshenig, Ph.D., Frank Dechend, Ph.D., Eva Schwaab, M.D., Jörg Schmidtke, M.D., Stephanie Schubert, Ph.D.

Volume 97, Issue 2 , Pages 402-406



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


Clinical article.


University hospital.


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.


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.


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.


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.

Read the full text at: