Mutations in CFAP43 and CFAP44 cause male infertility and flagellum defects in Trypanosoma and human
2018
Spermatogenesis defects concern millions of men worldwide, yet the vast majority remains undiagnosed. Here we report men with
primary infertilitydue to multiple morphological abnormalities of the sperm flagella with severe disorganization of the sperm
axoneme, a microtubule-based structure highly conserved throughout evolution. Whole-
exome sequencingwas performed on 78 patients allowing the identification of 22 men with bi-allelic mutations in DNAH1 (n = 6), CFAP43 (n = 10), and CFAP44 (n = 6).
CRISPR/
Cas9created homozygous CFAP43/44 male mice that were infertile and presented severe flagellar defects confirming the
human geneticresults. Immunoelectron and
stimulated-emission-depletion microscopy performed on CFAP43 and CFAP44 orthologs in
Trypanosoma bruceievidenced that both proteins are located between the doublet microtubules 5 and 6 and the paraflagellar rod. Overall, we demonstrate that CFAP43 and CFAP44 have a similar structure with a unique
axonemallocalization and are necessary to produce functional flagella in species ranging from
Trypanosomato human.
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