A comprehensive gene mutation screen in men with asthenozoospermia

To find novel genetic causes of asthenozoospermia by comprehensively screening known candidate genes derived from mouse models.

Case-control study.

A fertility center based in an academic hospital.

Thirty men with isolated asthenozoospermia.

Screening nine candidate genes for mutations: ADCY10, AKAP4, CATSPER1, CATSPER2, CATSPER3, CATSPER4, GAPDHS, PLA2G6, and SLC9A10. To account for a possible effect of heterozygous mutations, assessing imprinting of all candidate genes by studying the expression pattern of heterozygous SNPs in testis biopsies of five unrelated men.

Mutations found in patients only.

We identified 10 heterozygous asthenozoospermia-specific mutations in ADYC10 (n = 2), AKAP4 (n =1), CATSPER1 (n = 1), CATSPER2 (n = 1), CATSPER3 (n = 1), CATSPER4 (n = 3), and PLA2G6 (n = 1). These mutations were distributed over six patients. In silico analysis showed that 8 of the 10 mutations either had a negative BLOSUM score, were located in conserved residues, and/or were located in a functional domain. Expression analysis demonstrated that CATSPER1 and CATSPER4 are imprinted.

Given their putative effect on protein structure, their location in conserved sequences or functional domains, and their absence in controls, the identified mutations may be a cause of asthenozoospermia in humans.