{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T03:25:49Z","timestamp":1778815549255,"version":"3.51.4"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82394420"],"award-info":[{"award-number":["82394420"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82394423"],"award-info":[{"award-number":["82394423"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2703900"],"award-info":[{"award-number":["2022YFC2703900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder characterized by dysfunction of motile cilia. While approximately 50 genes have been identified, around 25% of PCD patients remain genetically unexplained; elucidating the pathogenicity of specific variants remains a challenge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole exome sequencing (WES) and Sanger sequencing were conducted to identify potential pathogenic variants of PCD. Minigene assays were performed to evaluate the pathogenicity of variants. Transmission electron microscopy (TEM) and high\u2010speed video analysis (HSVA) were conducted to analyze the function of cilia in respiratory epithelial cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified two variants of <jats:italic>DNAAF3<\/jats:italic>: c.557G&gt;A, p.G186E in exon 5, and c.1364G&gt;A, p.G455D at the terminal nucleotide of exon 10 in a 16\u2010year\u2010old male patient. Through a minigene assay, we demonstrated that the c.1364G&gt;A variant led to a four\u2010nucleotide skipping. The cilia in epithelial ciliary cells of the proband were almost immotile. The absence of outer dynein arms and inner dynein arms was also observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study identified two compound heterozygous variants of <jats:italic>DNAAF3<\/jats:italic>, a pathogenic gene for PCD, and proved that a novel missense variant c.1364G&gt;A affects splicing. Our findings not only expanded the spectrum of mutations in the <jats:italic>DNAAF3<\/jats:italic> gene but also highlighted the importance of investigating variants of uncertain significance (VUS) for comprehensive genetic diagnoses.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70036","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T10:19:52Z","timestamp":1736245192000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Interpreting Variants of Uncertain Significance in <scp>PCD<\/scp>: Abnormal Splicing Caused by a Missense Variant of <scp><i>DNAAF3<\/i><\/scp>"],"prefix":"10.1002","volume":"13","author":[{"given":"Haixia","family":"Zheng","sequence":"first","affiliation":[{"name":"McKusick\u2010Zhang Center for Genetic Medicine, State Key Laboratory for Complex Severe and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences School of Basic Medicine, Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chongsheng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"He","sequence":"additional","affiliation":[{"name":"McKusick\u2010Zhang Center for Genetic Medicine, State Key Laboratory for Complex Severe and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences School of Basic Medicine, Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wangji","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixuan","family":"Li","sequence":"additional","affiliation":[{"name":"McKusick\u2010Zhang Center for Genetic Medicine, State Key Laboratory for Complex Severe and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences School of Basic Medicine, Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinrong","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai\u2010Feng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Zhang","sequence":"additional","affiliation":[{"name":"McKusick\u2010Zhang Center for Genetic Medicine, State Key Laboratory for Complex Severe and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences School of Basic Medicine, Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinlun","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8274-7674","authenticated-orcid":false,"given":"Yaping","family":"Liu","sequence":"additional","affiliation":[{"name":"The State Key Laboratory for Complex Severe and Rare Diseases, the State Key Sci\u2010Tech Infrastructure for Translational Medicine Peking Union Medical College Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11632"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202109014"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5979"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20246174"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/children10020290"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00213\u20102020"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2021.02.006"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2020.05.052"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2020.11.040"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02300\u20102021"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073\u2010017\u20100403\u20107"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17946"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.138115.112"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388\u2010019\u20100968\u20102"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2020.11.007"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp698"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.34133\/research.0203"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.01.004"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2673"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.02.047"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01090\u20102016"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20102600(19)30374\u20101"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010020\u201002053\u20109"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1086\/302683"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2021.111359"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22105154"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201805\u20100819ST"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201904\u2010347OT"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010020\u20100766\u20109"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010020\u20100209\u20106"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.06.009"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073\u2010022\u201001019\u20109"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.70036","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T08:35:47Z","timestamp":1737707747000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.70036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/mgg3.70036"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.70036","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2024-02-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70036"}}