Multiple morphological abnormalities of flagella (MMAF) are human reproduction disorders due to the dysplastic development of sperm flagella. The spermatozoa of men with MMAF manifest absent, short, coiled, bent, and/or irregular-caliber flagella. Previous studies revealed genetic contributions to human MMAF, but known MMAF-associated genes only explained approximately 50% MMAF cases. In this study, we employed human whole-exome sequencing for genetic analysis and identified biallelic mutations of CFAP251 (cilia- and flagella-associated protein 251, also known as WDR66) in three (5%) of 65 Han Chinese men with MMAF. All these CFAP251 mutations are loss-of-function. The population genome data suggested that these CFAP251 mutations are extremely rare (only heterozygous) or absent from human populations. Our functional assays of gene expression and immunofluorescence staining in a CFAP251 -deficient man, together with previous experimental evidence from model organisms, suggested that CFAP251 is involved in flagellar functions. Our observations suggested that CFAP251 is associated with sperm flagellar development and human male infertility.
[1]Fudan Univ, Shanghai Inst Planned Parenthood Res, NHC Key Lab Reprod Regulat, Obstet & Gynecol Hosp,Sch Life Sci, Shanghai 200011, Peoples R China;
[2]Anhui Med Univ, Reprod Med Ctr, Dept Obstet & Gynecol, Affiliated Hosp 1, Hefei 230022, Anhui, Peoples R China;
[3]Anhui Med Univ, Anhui Prov Key Lab Reprod Hlth & Genet, Hefei 230022, Anhui, Peoples R China;
[4]Anhui Prov Engn Technol Res Ctr Biopreservat & Ar, Hefei 230022, Anhui, Peoples R China;
[5]Nanjing Med Univ, Ctr Reprod & Genet, Affiliated Suzhou Hosp, Suzhou 215002, Peoples R China;
[6]Suzhou Municipal Hosp, Suzhou 215002, Peoples R China;
[7]Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Nanjing 211116, Jiangsu, Peoples R China;
[8]Shanghai Key Lab Female Reprod Endocrine Related, Shanghai 200011, Peoples R China
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