{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:22:35Z","timestamp":1790965355697,"version":"4.1.0"},"reference-count":12,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Reprod. Health"],"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Multiple morphological abnormalities of the sperm flagella (MMAF) represents a rare and severe form of male infertility, characterized by defects in sperm flagella. Mutations in genes essential for flagellar function, such as\n                      <jats:italic>CFAP43<\/jats:italic>\n                      , have been implicated in MMAF. Flagella and motile cilia share a conserved axonemal structure essential for their motile function and the asthenospermia-related infertility of MMAF overlaps with primary ciliary dyskinesia (PCD) symptoms, characterized by chronic airway disease and infertility due to ciliary and flagellar dysfunction. This study investigates the genetic basis of MMAF in two siblings, who also exhibited respiratory symptoms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical assessment and semen analysis were conducted for two brothers presenting with infertility and chronic respiratory symptoms. Whole-exome sequencing (WES) was performed to identify potential genetic defects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both siblings exhibited classic MMAF features, including asthenospermia with various flagellar abnormalities, in addition to chronic respiratory symptoms including sinusitis and wet cough. WES identified a novel homozygous missense genetic variation in\n                      <jats:italic>CFAP43<\/jats:italic>\n                      [c.421T&amp;gt;A p.(Trp141Arg)].\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings provide additional evidence of the genetic contribution of\n                      <jats:italic>CFAP43<\/jats:italic>\n                      in MMAF and suggest an expanded phenotypic spectrum of\n                      <jats:italic>CFAP43<\/jats:italic>\n                      -associated conditions to encompass chronic respiratory symptoms attributed to airway ciliary dysfunction. Further research is needed to uncover the underlying mechanisms linking\n                      <jats:italic>CFAP43<\/jats:italic>\n                      mutations to these phenotypes.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/frph.2025.1609938","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T06:22:38Z","timestamp":1763446958000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Expanding the phenotypic spectrum associated with CFAP43 mutations: a case report of familial male infertility with respiratory manifestations"],"prefix":"10.3389","volume":"7","author":[{"given":"Fawaz","family":"Awad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razan","family":"Abukhaizaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahira","family":"Al Jabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Nabilsi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laith A.","family":"Ayasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majd A.","family":"AbuAlrob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haneen","family":"Owienah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanin","family":"Kassem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moien","family":"Kanaan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e13874","DOI":"10.1111\/and.13874","article-title":"Sperm DNA fragmentation testing: summary evidence and clinical practice recommendations","volume":"53","author":"Esteves","year":"2021","journal-title":"Andrologia"},{"key":"B2","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.ajhg.2013.11.017","article-title":"Mutations in DNAH1, which 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Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1007\/s00439-020-02110-0","article-title":"Novel mutations in SPEF2 causing different defects between flagella and cilia bridge: the phenotypic link between MMAF and PCD","volume":"139","author":"Tu","year":"2020","journal-title":"Hum Genet"}],"container-title":["Frontiers in Reproductive 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