{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T20:41:15Z","timestamp":1786653675866,"version":"build-2736575974"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:p>\n                    Multiple morphological abnormalities of sperm flagellum (MMAF) is a rare cause of primary infertility. Genetic variants in cilia- and flagella-associated protein 43 (\n                    <jats:italic toggle=\"yes\">CFAP43<\/jats:italic>\n                    ) are associated with asthenoteratospermia and MMAF; however, the detailed pathogenic mechanisms are still to be completely elucidated. Here, we identified novel compound heterozygous mutations in\n                    <jats:italic toggle=\"yes\">CFAP43<\/jats:italic>\n                    , c.1859_1860+8delinsGT, and c.3071A&gt;G (p.N1024S), by whole-exome sequencing (WES). The proband had a typical MMAF phenotype; Sanger sequencing confirmed these mutations and showed that they cosegregated within the family. Further analysis of the patient\u2019s sperm samples indicated that the\n                    <jats:italic toggle=\"yes\">CFAP43<\/jats:italic>\n                    mutations result in aberrant RNA splicing. Additionally, we observed disturbance and partial deletion of the mitochondrial sheath, along with a significant reduction in translocase of outer mitochondrial membrane 20 (TOM20) expression. This study suggests that infertility associated with CFAP43 loss of function may be linked to mitochondrial dysfunction. Finally, assisted reproductive technology using intracytoplasmic sperm injection (ICSI) resulted in a successful pregnancy and live birth. Our study expands the spectrum of pathogenic\n                    <jats:italic toggle=\"yes\">CFAP43<\/jats:italic>\n                    mutations and provides valuable insights for genetic counseling and personalized reproductive strategies in patients with MMAF.\n                  <\/jats:p>","DOI":"10.4103\/aja202565","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T06:00:09Z","timestamp":1768802409000},"page":"327-334","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Novel biallelic CFAP43 mutations induce MMAF with mitochondrial abnormalities and successful ICSI outcomes"],"prefix":"10.4103","volume":"28","author":[{"given":"Qi","family":"Chen","sequence":"first","affiliation":[{"name":"Reproductive Center, Northwest Women\u2019s and Children\u2019s Hospital, Xi\u2019an 710000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yang","sequence":"additional","affiliation":[{"name":"Reproductive Center, Northwest Women\u2019s and Children\u2019s Hospital, Xi\u2019an 710000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Jia","family":"Shi","sequence":"additional","affiliation":[{"name":"Reproductive Center, Northwest Women\u2019s and Children\u2019s Hospital, Xi\u2019an 710000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Chun","family":"Wu","sequence":"additional","affiliation":[{"name":"Reproductive Center, Northwest Women\u2019s and Children\u2019s Hospital, Xi\u2019an 710000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Ren","sequence":"additional","affiliation":[{"name":"Reproductive Center, Northwest Women\u2019s and Children\u2019s Hospital, Xi\u2019an 710000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xue","sequence":"additional","affiliation":[{"name":"Reproductive Center, Northwest Women\u2019s and Children\u2019s Hospital, Xi\u2019an 710000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing-Zhe","family":"Ji","sequence":"additional","affiliation":[{"name":"Reproductive Center, Northwest Women\u2019s and Children\u2019s Hospital, Xi\u2019an 710000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine, AmCare Genomics Lab, Guangzhou 510005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Cai","sequence":"additional","affiliation":[{"name":"Reproductive Center, Northwest Women\u2019s and Children\u2019s Hospital, Xi\u2019an 710000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan-Zi","family":"Shi","sequence":"additional","affiliation":[{"name":"Reproductive Center, Northwest Women\u2019s and Children\u2019s Hospital, Xi\u2019an 710000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen","family":"Qiao","sequence":"additional","affiliation":[{"name":"Reproductive Center, Northwest Women\u2019s and Children\u2019s Hospital, Xi\u2019an 710000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"R1-20260430","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/j.ajhg.2017.04.012","article-title":"Biallelic mutations in CFAP43 and CFAP44 cause male infertility with multiple morphological abnormalities of the sperm flagella","volume":"100","author":"Tang","year":"2017","journal-title":"Am J Hum Genet"},{"key":"R2-20260430","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/s41467-017-02792-7","article-title":"Mutations in CFAP43 and CFAP44 cause male infertility and flagellum defects in Trypanosoma and human","volume":"9","author":"Coutton","year":"2018","journal-title":"Nat Commun"},{"key":"R3-20260430","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/S0015-0282(16)59482-5","article-title":"Dysplasia of the fibrous sheath:an ultrastructural defect of human spermatozoa associated with sperm immotility and primary sterility","volume":"48","author":"Chemes","year":"1987","journal-title":"Fertil Steril"},{"key":"R4-20260430","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1093\/humrep\/16.5.879","article-title":"Incidence of tail structure distortions associated with dysplasia of the fibrous sheath in human spermatozoa","volume":"16","author":"Rawe","year":"2001","journal-title":"Hum Reprod"},{"key":"R5-20260430","doi-asserted-by":"crossref","first-page":"e13151","DOI":"10.1111\/and.13151","article-title":"Patients with multiple morphological abnormalities of the sperm flagella harbouring CFAP44 or CFAP43 mutations have a good pregnancy outcome following intracytoplasmic sperm injection","volume":"51","author":"Sha","year":"2019","journal-title":"Andrologia"},{"key":"R6-20260430","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/j.1439-0272.1990.tb02020.x","article-title":"Tail stump spermatozoa:morphogenesis of the defect. An ultrastructural study of sperm and testicular biopsy","volume":"22","author":"Barthelemy","year":"1990","journal-title":"Andrologia"},{"key":"R7-20260430","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s12610-019-0083-9","article-title":"Genetic causes of male infertility:snapshot on morphological abnormalities of the sperm flagellum","volume":"29","author":"Nsota Mbango","year":"2019","journal-title":"Basic Clin Androl"},{"key":"R8-20260430","doi-asserted-by":"crossref","first-page":"564","DOI":"10.4103\/aja2022118","article-title":"Patients with MMAF induced by novel biallelic CFAP43 mutations have good fertility outcomes after intracytoplasmic sperm injection","volume":"25","author":"Ma","year":"2023","journal-title":"Asian J Androl"},{"key":"R9-20260430","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.ajhg.2018.03.007","article-title":"Absence of CFAP69 causes male infertility due to multiple morphological abnormalities of the flagella in human and mouse","volume":"102","author":"Dong","year":"2018","journal-title":"Am J Hum Genet"},{"key":"R10-20260430","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1093\/hmg\/ddy034","article-title":"Homozygous missense mutation L673P in adenylate kinase 7 (AK7) leads to primary male infertility and multiple morphological anomalies of the flagella but not to primary ciliary dyskinesia","volume":"27","author":"Lor\u00e8s","year":"2018","journal-title":"Hum Mol Genet"},{"key":"R11-20260430","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1002\/j.1939-4640.2001.tb02184.x","article-title":"Molecular genetic analysis of two human sperm fibrous sheath proteins, AKAP4 and AKAP3, in men with dysplasia of the fibrous sheath","volume":"22","author":"Turner","year":"2001","journal-title":"J Androl"},{"key":"R12-20260430","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/j.scib.2020.01.023","article-title":"Absence of murine CFAP61 causes male infertility due to multiple morphological abnormalities of the flagella","volume":"65","author":"Huang","year":"2020","journal-title":"Sci Bull"},{"key":"R13-20260430","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/s41421-021-00327-5","article-title":"Bi-allelic variants in human WDR63 cause male infertility via abnormal inner dynein arms assembly","volume":"7","author":"Lu","year":"2021","journal-title":"Cell Discov"},{"key":"R14-20260430","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/s41467-018-08182-x","article-title":"Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella","volume":"10","author":"Shen","year":"2019","journal-title":"Nat Commun"},{"key":"R15-20260430","doi-asserted-by":"crossref","first-page":"1155639","DOI":"10.3389\/fendo.2023.1155639","article-title":"A novel mutation in CFAP47 causes male infertility due to multiple morphological abnormalities of the sperm 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infertility","volume":"27","author":"Zhou","year":"2025","journal-title":"Asian J Androl"},{"key":"R19-20260430","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1177\/1933719117749756","article-title":"Novel mutations in CFAP44 and CFAP43 cause multiple morphological abnormalities of the sperm flagella (MMAF)","volume":"26","author":"Sha","year":"2019","journal-title":"Reprod Sci"},{"key":"R21-20260430","doi-asserted-by":"crossref","first-page":"236","DOI":"10.4103\/aja.aja_53_19","article-title":"Insight on multiple morphological abnormalities of sperm flagella in male infertility:what is new?","volume":"22","author":"Wang","year":"2020","journal-title":"Asian J Androl"},{"key":"R22-20260430","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1017\/S0967199420000556","article-title":"CFAP43-mediated intra-manchette transport is required for sperm head shaping and flagella 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