A comprehensive gene mutation screen in men with asthenozoospermia

作者：Visser Lie**eth; Westerveld G Henrike; Xie Fang; van Daalen Saskia K M; van der Veen Fulco; Lombardi M Paola; Repping Sjoerd^*

来源：Fertility and Sterility, 2011, 95(3): 1020-U213.

DOI：10.1016/j.fertnstert.2010.11.067

• Asthenozoospermia
• gene
• male infertility
• spermatogenesis

Objective: To find novel genetic causes of asthenozoospermia by comprehensively screening known candidate genes derived from mouse models.
Design: Case-control study.
Setting: A fertility center based in an academic hospital.
Patient(s): Thirty men with isolated asthenozoospermia.
Intervention(s): 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.
Main Outcome Measure(s): Mutations found in patients only.
Result(s): We identified 10 heterozygous asthenozoospermia-specific mutations inADYC10 (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.
Conclusion(s): 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. (Fertil Steril (R) 2011;95:1020-24.

• 出版日期2011-3