Mutation screening and association study of the TSSK4 Gene in Chinese infertile men with impaired spermatogenesis.

The testis-specific serine/threonine kinase (TSSK) family is a specific kinase group with exclusive or dominant expression in testis and involvement in spermatogenesis and male infertility. TSSK4 is a newly identified member of the TSSK family. In order to investigate the possible relationships between variations, including mutations and polymorphisms of the TSSK4 gene and impaired spermatogenesis in humans, mutation screening of this gene in 372 patients with azoospermia or severe oligospermia and 220 controls was performed. In total, 4 novel single nucleotide changes including c.679G>A, c.987+108G>A, c.-155C>G and c.765C>A were discovered. The latter 2 variations were found only in patients, not in controls. Bioinformatics analysis suggested that allele A of c.765C>A could decrease the activity of pre-mRNA splicing of TSSK4. The frequency of allele A of c.679G>A was significantly higher in controls than in patients. On the contrary, allele A of c.987+108G>A was remarkably increased in patients compared with controls. Our investigation of TSSK4, a potentially important testicular gene, in Chinese infertile and control men identified the association of some single nucleotide polymorphisms in this gene with male infertility.