{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:28:33Z","timestamp":1790616513514,"version":"4.1.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Multiple morphological abnormalities of the sperm flagella (MMAF) is a specific type of asthenoteratozoospermia, presenting with multiple morphological anomalies in spermatozoa, such as absent, bent, coiled, short, or irregular caliber flagella. Previous genetic studies revealed pathogenic mutations in genes encoding cilia and flagella-associated proteins (\n                      <jats:italic toggle=\"yes\">CFAPs<\/jats:italic>\n                      ;\n                      <jats:italic toggle=\"yes\">e.g<\/jats:italic>\n                      .,\n                      <jats:italic toggle=\"yes\">CFAP43<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">CFAP44<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">CFAP65<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">CFAP69<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">CFAP70<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">CFAP251<\/jats:italic>\n                      ) responsible for the MMAF phenotype in infertile men from different ethnic groups. However, none of them have been identified in infertile Pakistani males with MMAF. In the current study, two Pakistani families with MMAF patients were recruited. Whole-exome sequencing (WES) of patients and their parents was performed. WES analysis reflected novel biallelic loss-of-function mutations in\n                      <jats:italic toggle=\"yes\">CFAP43<\/jats:italic>\n                      in both families (Family 1: ENST00000357060.3, p.Arg300Lysfs*22 and p.Thr526Serfs*43 in a compound heterozygous state; Family 2: ENST00000357060.3, p.Thr526Serfs*43 in a homozygous state). Sanger sequencing further confirmed that these mutations were segregated recessively in the families with the MMAF phenotype. Semiquantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was carried out to detect the effect of the mutation on mRNA of the affected gene. Previous research demonstrated that biallelic loss-of-function mutations in\n                      <jats:italic toggle=\"yes\">CFAP43<\/jats:italic>\n                      accounted for the majority of all\n                      <jats:italic toggle=\"yes\">CFAP43<\/jats:italic>\n                      -mutant MMAF patients. To the best of our knowledge, this is the first study to report\n                      <jats:italic toggle=\"yes\">CFAP43<\/jats:italic>\n                      biallelic loss-of-function mutations in a Pakistani population with the MMAF phenotype. This study will help researchers and clinicians to understand the genetic etiology of MMAF better.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/aja.aja_26_21","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T22:01:17Z","timestamp":1621288877000},"page":"627-632","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":21,"title":["Novel biallelic loss-of-function mutations in CFAP43 cause multiple morphological abnormalities of the sperm flagellum in Pakistani families"],"prefix":"10.4103","volume":"23","author":[{"given":"Ihsan","family":"Khan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basit","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sobia","family":"Dil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadeem","family":"Ullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Teng","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da-Ren","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Wei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Hua","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjha","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asad","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haider","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Zubair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wasim","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Hua","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-13-20240829","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s00439-020-02113-x","article-title":"The genetic architecture of morphological abnormalities of the sperm tail","volume":"140","author":"Tour\u00e9","year":"2021","journal-title":"Hum Genet"},{"key":"R2-13-20240829","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":"R3-13-20240829","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":"R4-13-20240829","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":"R5-13-20240829","doi-asserted-by":"crossref","first-page":"131","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":"R6-13-20240829","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. 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