Mutational effect of human CFAP43 splice-site variant causing multiple morphological abnormalities of the sperm flagella.

Multiple morphological abnormalities of the sperm flagella (MMAF) is a rare disease associated with male infertility. In our previous study, we identified a homozygous CFAP43 splice-site variant, c.3661-2delA, in a patient with MMAF. However, the mutational effect of this variant was unknown. Here, using a minigene assay, we demonstrated that the c.3661-2delA variant may cause exon-30 to be skipped, thus generating the p.E1221_K1256del protein. By secondary and three-dimensional structural biology prediction analysis, we found that the mutant protein became 'tighter' in comparison with the wild-type protein, resulting in amino acid rearrangements in CFAP43 protein structure. We elucidated the molecular mechanism of the c.3661-2delA splice-site variant causing MMAF in the current study.