• PMID: 21255775
• Gene Name: CatSper1
• Condition: Asthenozoospermia
• Association: The study 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)
• Mutation: AKAP4 (c.887G>A -> p.Gly296Asn), CATSPER4 (c.247A>G -> p.Met83Val; c.157T>C -> p.Tyr53His; c.992G>A -> p.Gly331Asn), CATSPER1 (c.148G>A -> p.Val50Met), CATSPER3 (c.193T>C -> p.Phe65Leu), CATSPER2 (c.1289C>G -> p.Thr430Arg), PLA2G6 (c.187A>G -> p.Arg63Gly
• Population size: 30
• Population details: 30 men with isolated asthenozoospermia
• Sex: Male
• Infertility type: Male infertility
• Associated genes: ADCY10, AKAP4, CATSPER1, CATSPER2, CATSPER3, CATSPER4, GAPDHS, PLA2G6, and SLC9A10
• Other associated phenotypes: Asthenozoospermia

A comprehensive gene mutation screen in men with asthenozoospermia

Visser L, Westerveld GH, Xie F, van Daalen SK, van der Veen F, Lombardi MP, Repping S.

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 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. 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. CI - Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. FAU - Visser, Liesbeth AU - Visser L AD - Department of Obstetrics and Gynaecology, Center for Reproductive Medicine, Amsterdam, the Netherlands. FAU - Westerveld, G Henrike AU - Westerveld GH FAU - Xie, Fang AU - Xie F FAU - van Daalen, Saskia K M AU - van Daalen SK FAU - van der Veen, Fulco AU - van der Veen F FAU - Lombardi, M Paola AU - Lombardi MP