{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T07:59:47Z","timestamp":1780646387908,"version":"3.54.1"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100024211","name":"Ac\u0131badem Mehmet ali Ayd\u0131nlar \u00dcniversitesi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100024211","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Primary ciliary dyskinesia (PCD) is a rare genetic disorder affecting approximately 1:15,000 to 1:30,000 individuals. It is characterized by upper and lower respiratory diseases, otitis media, congenital heart defects, situs inversus, infertility in males, and hydrocephalus. Whole-exome sequencing (WES) has become an important tool for identifying novel pathogenic variants associated with PCD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Trio-based WES was performed in two Turkish siblings with clinically suspected PCD born to healthy consanguineous parents. Candidate variants were validated by Sanger sequencing and functionally assessed using immunofluorescence (IF) analysis of respiratory cilia obtained by nasal brushing biopsy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A novel homozygous frameshift pathogenic variant in\n                      <jats:italic>ARMC4<\/jats:italic>\n                      [c.324dupA; p.Arg109Thrfs*19] was identified in both affected siblings. IF analysis demonstrated absence of\n                      <jats:italic>ARMC4<\/jats:italic>\n                      protein in the ciliary axonemes and distal loss of DNAH5, confirming the functional effect of the variant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      These findings expand the mutational spectrum of\n                      <jats:italic>ARMC4<\/jats:italic>\n                      -associated PCD and highlight the importance of combining genetic and functional analyses for accurate diagnosis and variant interpretation in PCD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmolb.2026.1815627","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T04:28:14Z","timestamp":1780374494000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel pathogenic variant in ARMC4 identified by whole exome sequencing in a Turkish family with primary ciliary dyskinesia"],"prefix":"10.3389","volume":"13","author":[{"given":"Elif Arik","family":"Sever","sequence":"first","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Graduate School of Health Sciences, Acibadem Mehmet Ali Aydinlar University","place":["Istanbul, T\u00fcrkiye"]},{"name":"Department of Medical Biology and Genetics, School of Medicine, Okan University","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rim","family":"Hjeij","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, University Children\u2019s Hospital Muenster","place":["Muenster, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u0131nar","family":"Ata","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, School of Medicine, Marmara University","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ela Erdem","family":"Eralp","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology, School of Medicine, Marmara University","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emine","family":"Atag","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology, School of Medicine, Maltepe University","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heymut","family":"Omran","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, University Children\u2019s Hospital Muenster","place":["Muenster, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bulent Taner","family":"Karada\u01e7","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology, School of Medicine, Marmara University","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osman Ugur","family":"Sezerman","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Graduate School of Health Sciences, Acibadem Mehmet Ali Aydinlar University","place":["Istanbul, T\u00fcrkiye"]},{"name":"Department of Biostatistics and Medical Informatics, School of Medicine, Acibadem Mehmet Ali Aydinlar University","place":["Istanbul, T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat. 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