A comprehensive gene mutation screen in men with asthenozoospermia.
OBJECTIVE
To find novel genetic causes of asthenozoospermia by comprehensively screening known candidate genes derived from mouse models.


METHODS
Case-control study.


METHODS
A fertility center based in an academic hospital.


METHODS
Thirty men with isolated asthenozoospermia.


METHODS
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.


METHODS
Mutations found in patients only.


RESULTS
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.


CONCLUSIONS
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.
Department of Obstetrics and Gynaecology, Center for Reproductive Medicine, Amsterdam, the Netherlands.
Liesbeth
L
Visser
G Henrike
GH
Westerveld
Fang
F
Xie
Saskia K M
SK
van Daalen
Fulco
F
van der Veen
M Paola
MP
Lombardi
Sjoerd
S
Repping
D000328:Adult; D000818:Animals; D053627:Asthenozoospermia / Q000235:genetics* / Q000473:pathology*; D001483:Base Sequence; D001706:Biopsy; D016022:Case-Control Studies; D005820:Genetic Testing / Q000379:methods*; D018392:Genomic Imprinting; D006579:Heterozygote; D006801:Humans; D008297:Male; D051379:Mice; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000473:pathology