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Mutational effect of human CFAP43 splice‐site variant causing multiple morphological abnormalities of the sperm flagella
Author(s) -
Li Lin,
Feng Fan,
Wang Yipeng,
Guo Jianying,
Yue Wentao
Publication year - 2020
Publication title -
andrologia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.633
H-Index - 59
eISSN - 1439-0272
pISSN - 0303-4569
DOI - 10.1111/and.13575
Subject(s) - biology , minigene , flagellum , splice , genetics , rna splicing , exon , mutant , sperm , gene , rna
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.