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• W2617398306 abstract "Sperm motility is vital to human reproduction. Malformations of sperm flagella can cause male infertility. Men with multiple morphological abnormalities of the flagella (MMAF) have abnormal spermatozoa with absent, short, coiled, bent, and/or irregular-caliber flagella, which impair sperm motility. The known human MMAF-associated genes, such as DNAH1, only account for fewer than 45% of affected individuals. Pathogenic mechanisms in the genetically unexplained MMAF remain to be elucidated. Here, we conducted genetic analyses by using whole-exome sequencing and genome-wide comparative genomic hybridization microarrays in a multi-center cohort of 30 Han Chinese men affected by MMAF. Among them, 12 subjects could not be genetically explained by any known MMAF-associated genes. Intriguingly, we identified compound-heterozygous mutations in CFAP43 in three subjects and a homozygous frameshift mutation in CFAP44 in one subject. All of these recessive mutations were parentally inherited from heterozygous carriers but were absent in 984 individuals from three Han Chinese control populations. CFAP43 and CFAP44, encoding two cilia- and flagella-associated proteins (CFAPs), are specifically or preferentially expressed in the testis. Using CRISPR/Cas9 technology, we generated two knockout models each deficient in mouse ortholog Cfap43 or Cfap44. Notably, both Cfap43- and Cfap44-deficient male mice presented with MMAF phenotypes, whereas the corresponding female mice were fertile. Our experimental observations on human subjects and animal models strongly suggest that biallelic mutations in either CFAP43 or CFAP44 can cause sperm flagellar abnormalities and impair sperm motility. Further investigations on other CFAP-encoding genes in more genetically unexplained MMAF-affected individuals could uncover novel mechanisms underlying sperm flagellar formation. Sperm motility is vital to human reproduction. Malformations of sperm flagella can cause male infertility. Men with multiple morphological abnormalities of the flagella (MMAF) have abnormal spermatozoa with absent, short, coiled, bent, and/or irregular-caliber flagella, which impair sperm motility. The known human MMAF-associated genes, such as DNAH1, only account for fewer than 45% of affected individuals. Pathogenic mechanisms in the genetically unexplained MMAF remain to be elucidated. Here, we conducted genetic analyses by using whole-exome sequencing and genome-wide comparative genomic hybridization microarrays in a multi-center cohort of 30 Han Chinese men affected by MMAF. Among them, 12 subjects could not be genetically explained by any known MMAF-associated genes. Intriguingly, we identified compound-heterozygous mutations in CFAP43 in three subjects and a homozygous frameshift mutation in CFAP44 in one subject. All of these recessive mutations were parentally inherited from heterozygous carriers but were absent in 984 individuals from three Han Chinese control populations. CFAP43 and CFAP44, encoding two cilia- and flagella-associated proteins (CFAPs), are specifically or preferentially expressed in the testis. Using CRISPR/Cas9 technology, we generated two knockout models each deficient in mouse ortholog Cfap43 or Cfap44. Notably, both Cfap43- and Cfap44-deficient male mice presented with MMAF phenotypes, whereas the corresponding female mice were fertile. Our experimental observations on human subjects and animal models strongly suggest that biallelic mutations in either CFAP43 or CFAP44 can cause sperm flagellar abnormalities and impair sperm motility. Further investigations on other CFAP-encoding genes in more genetically unexplained MMAF-affected individuals could uncover novel mechanisms underlying sperm flagellar formation." @default.
• W2617398306 created "2017-06-05" @default.
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• W2617398306 date "2017-06-01" @default.
• W2617398306 modified "2023-10-16" @default.
• W2617398306 title "Biallelic Mutations in CFAP43 and CFAP44 Cause Male Infertility with Multiple Morphological Abnormalities of the Sperm Flagella" @default.
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• W2617398306 cites W1970413157 @default.
• W2617398306 cites W1973632178 @default.
• W2617398306 cites W1980740976 @default.
• W2617398306 cites W1984068087 @default.
• W2617398306 cites W1988837133 @default.
• W2617398306 cites W1997381325 @default.
• W2617398306 cites W2001554877 @default.
• W2617398306 cites W2028183762 @default.
• W2617398306 cites W2031379358 @default.
• W2617398306 cites W2046932648 @default.
• W2617398306 cites W2054175870 @default.
• W2617398306 cites W2059145105 @default.
• W2617398306 cites W2059707376 @default.
• W2617398306 cites W2061680337 @default.
• W2617398306 cites W2064815984 @default.
• W2617398306 cites W2070387100 @default.
• W2617398306 cites W2096791516 @default.
• W2617398306 cites W2097907753 @default.
• W2617398306 cites W2103017472 @default.
• W2617398306 cites W2103441770 @default.
• W2617398306 cites W2116633428 @default.
• W2617398306 cites W2118192474 @default.
• W2617398306 cites W2119180969 @default.
• W2617398306 cites W2120077307 @default.
• W2617398306 cites W2124608202 @default.
• W2617398306 cites W2126879318 @default.
• W2617398306 cites W2129639344 @default.
• W2617398306 cites W2133948311 @default.
• W2617398306 cites W2135979384 @default.
• W2617398306 cites W2154261437 @default.
• W2617398306 cites W2160721292 @default.
• W2617398306 cites W2162927194 @default.
• W2617398306 cites W2166977115 @default.
• W2617398306 cites W2169101403 @default.
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• W2617398306 doi "https://doi.org/10.1016/j.ajhg.2017.04.012" @default.
• W2617398306 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5473723" @default.
• W2617398306 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28552195" @default.
• W2617398306 hasPublicationYear "2017" @default.
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