A novel recurrent mutation in CFAP47 causes male infertility with asthenoteratozoospermia

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 ( CFAP4 7, 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.