Novel mutations in testis-specific ubiquitin protease 26 gene may cause male infertility and hypogonadism.

Patients (n = 188) with non-obstructive azoospermia (NOA), and 17 fertile controls were screened for sequence changes in the ubiquitin specific protease (USP) 26 gene. Semen analysis, hormonal evaluation, and testicular biopsies were performed. DNA was extracted from whole blood. Denaturing high-performance liquid chromatography was used to screen for single nucleotide polymorphisms. Amino acid sequences were determined in samples with mutations. Twenty out of 188 (10.6%) infertile men had amino acid changes in USP26. No changes were found in fertile controls. 1090C-->T substitution and (363insACA; 494T-->C; 1423C-->T) change were found in 3.3 and 1.9% of patients respectively. Serum testosterone concentrations and testicular volume were lower in the mutation positive group compared with the non-mutation group (272 versus 366 ng/dl; P = 0.01) (volume: 7.88 versus 10 ml, P = 0.03). Six out of 28 (21%) patients with Sertoli cell-only syndrome, and two out of 18 (11%) patients with maturation arrest had mutations in the USP26 gene. There were no live deliveries in couples with the USP26+ mutation, and three live deliveries in the group without mutations. The USP26 gene may be of importance in male reproduction. Mutations in this gene may be associated with male infertility, and may negatively affect testicular function.