A novel recurrent mutation in CFAP47 causes male infertility with
asthenoteratozoospermia
Abstract
Multiple morphological abnormalities of the sperm flagella (MMAF) is an
important cause of male infertility and is defined as absent, short,
coiled, bent irregular flagella. In this study, we identified a novel
missense mutation (c.1414G>A; p.V472M) in Cilia and
flagella associated protein 47( CFAP47, NG_016381.2) in two
unrelated patients with asthenoteratozoospermia. In addition to the
typical MMAF phenotype very analogous to that of Cfap47 mutant
male mice, the two patients also presented abnormal morphology of sperm
heads, mitochondrial sheath disorganization, and defects of sperm
annulus. Further functional experiments confirmed that the expression of
CFAP47 was markedly reduced in the spermatozoa of the patients.
Moreover, coimmunoprecipitation and immunofluorescence showed that
CFAP47 might regulate CFAP65 and CFAP69 through physical interactions
and is thus involved in sperm morphogenesis. In conclusion, we reveal a
novel recurrent mutation in CFAP47 and further expand the
clinical and mutational spectrum of CFAP47, finally providing
important guidance for genetic counseling and targeted treatment.