{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T21:44:10Z","timestamp":1774129450798,"version":"3.50.1"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T00:00:00Z","timestamp":1664409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171948"],"award-info":[{"award-number":["82171948"]}],"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":["81970264"],"award-info":[{"award-number":["81970264"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"publisher","award":["20214Y0126"],"award-info":[{"award-number":["20214Y0126"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008233","name":"School of Medicine, Shanghai Jiao Tong University","doi-asserted-by":"publisher","award":["21XJMR04"],"award-info":[{"award-number":["21XJMR04"]}],"id":[{"id":"10.13039\/501100008233","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by motile ciliary dysfunction and impaired ultrastructure. Despite numerous studies, the genetic basis for about 30% of PCD cases remains to be elucidated. Here, we present the identification and functional analysis of two novel mutations in the gene encoding coiled-coil domain-containing protein 40 (CCDC40), which are found in a familial case of PCD. These novel <jats:italic>CCDC40<\/jats:italic> mutations, NM_017950.4: c.2236-2delA and c.2042_2046delTCACA, NP_060420.2: p.(Ile681fs), were identified by whole-exome sequencing (WES). Sanger sequencing was then performed to confirm the WES results and determine the <jats:italic>CCDC40<\/jats:italic> gene sequences of the proband\u2019s parents. The c.2042_2046delTCACA mutation disrupts the reading frame of the protein and is therefore predicted to produce a non-functional protein. Using a minigene assay with the pcDNA3.1(+) plasmid, we further investigated the potential pathogenic effects of the c.2236-2delA mutation and found that this mutation leads to formation of a truncated protein <jats:italic>via<\/jats:italic> splicing disruption. Thus, in summary, we identified two mutations of the <jats:italic>CCDC40<\/jats:italic> gene that can be considered pathogenic compound heterozygous mutations in a case of familial PCD, thereby expanding the known mutational spectrum of the <jats:italic>CCDC40<\/jats:italic> gene in this disease.<\/jats:p>","DOI":"10.3389\/fped.2022.996332","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T07:40:57Z","timestamp":1664437257000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel compound heterozygous CCDC40 mutations in a familial case of primary ciliary dyskinesia"],"prefix":"10.3389","volume":"10","author":[{"given":"Liqing","family":"Zhao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suqiu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingyao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenxiang","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongzhou","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yurong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1136\/adc.2006.096958","article-title":"Primary 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