{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T11:22:49Z","timestamp":1792149769578,"version":"4.4.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T00:00:00Z","timestamp":1646006400000},"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. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Primary ciliary dyskinesia (PCD) is a rare genetically heterogeneous disorder of motile cilia. Common features of PCD include upper and lower respiratory tract disease, secretory otitis media, situs inversus and fertility problems. To date, although several PCD-associated genes have been identified, the genetic causes of most PCD cases remain elusive.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> In this case study, we analyzed the clinical and genetic data of one case of monochorionic diamniotic twins which were suspected of having PCD on the basis of clinical and radiological features including situs inversus, recurrent wet cough and sinusitis as well as varying degrees of respiratory distress. Whole-exome sequencing was performed to identify variants of the <jats:italic>DNAH11<\/jats:italic> gene in the twins. Sanger sequencing and real-time quantitative polymerase chain reaction (RT-qPCR) were used for validation of <jats:italic>DNAH11<\/jats:italic> variants both in the patient and the twins.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> In the twins, we found a novel mutation at c.2436C &amp;gt; G (p.Y812 *) and a pathogenic deletion encompassing 2.0\u00a0Kb of 7P15.3 ([GRCh38] chr7: g.21,816,397-21,818,402). The deleted region included exons 64 and 65 of <jats:italic>DNAH11<\/jats:italic>. Sanger sequencing also revealed that the twins\u2019 father was a carrier of heterozygous C.2436C &amp;gt; G and a heterozygous deletion was detected in the mother. No other clinically relevant genetic variants were identified.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> We describe a novel <jats:italic>DNAH11<\/jats:italic> gene compound heterozygous mutation in newborn twins with PCD and recommend that PCD diagnosis should be considered in newborns presenting with respiratory distress and\/or situs inversus. Early diagnosis and treatment of PCD will help control disease progression and improve the patient\u2019s quality of life.<\/jats:p>","DOI":"10.3389\/fgene.2022.814511","type":"journal-article","created":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T10:21:39Z","timestamp":1646043699000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["A Novel Compound Heterozygous Mutation in the DNAH11 Gene Found in Neonatal Twins With Primary Ciliary Dyskinesis"],"prefix":"10.3389","volume":"13","author":[{"given":"Shumei","family":"Dong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Bei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luming","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiafang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1038\/nature01377","article-title":"Dynein Structure and Power Stroke","volume":"421","author":"Burgess","year":"2003","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1517\/21678707.2015.989212","article-title":"Genetics, Diagnosis and Future Treatment Strategies for Primary Ciliary Dyskinesia","volume":"3","author":"Daniels","year":"2015","journal-title":"Expert Opin. Orphan Drugs"},{"key":"B3","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1165\/rcmb.2015-0353OC","article-title":"DNAH11 Localization in the Proximal Region of Respiratory Cilia Defines Distinct Outer Dynein Arm Complexes","volume":"55","author":"Dougherty","year":"2016","journal-title":"Am. J. Respir. Cel Mol Biol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1183\/13993003.00736-2016","article-title":"Clinical Manifestations in Primary Ciliary Dyskinesia: Systematic Review and Meta-Analysis","volume":"48","author":"Goutaki","year":"2016","journal-title":"Eur. Respir. J."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1768","DOI":"10.1016\/j.chest.2021.02.006","article-title":"Clinical and Genetic Spectrum of Children with Primary Ciliary Dyskinesia in China","volume":"159","author":"Guan","year":"2021","journal-title":"Chest"},{"key":"B6","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.jpeds.2020.05.052","article-title":"Clinical and Genetic Spectrum of Children with Primary Ciliary Dyskinesia in China","volume":"225","author":"Guo","year":"2020","journal-title":"J. Pediatr."},{"key":"B7","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.ydbio.2011.03.009","article-title":"Left-right Asymmetry in the Level of Active Nodal Protein Produced in the Node Is Translated into Left-Right Asymmetry in the Lateral Plate of Mouse Embryos","volume":"353","author":"Kawasumi","year":"2011","journal-title":"Dev. Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1136\/thoraxjnl-2011-200301","article-title":"Mutations ofDNAH11in Patients with Primary Ciliary Dyskinesia with normal Ciliary Ultrastructure","volume":"67","author":"Knowles","year":"2012","journal-title":"Thorax"},{"key":"B9","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1136\/jmedgenet-2015-103539","article-title":"Gene Editing ofDNAH11restores normal Cilia Motility in Primary Ciliary Dyskinesia","volume":"53","author":"Lai","year":"2016","journal-title":"J. Med. Genet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1038\/ncb2939","article-title":"Structural Mechanism of the Dynein Power Stroke","volume":"16","author":"Lin","year":"2014","journal-title":"Nat. Cel Biol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1136\/archdischild-2013-304831","article-title":"Diagnosis and Management of Primary Ciliary Dyskinesia","volume":"99","author":"Lucas","year":"2014","journal-title":"Arch. Dis. Child."},{"key":"B12","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/S2213-2600(19)30374-1","article-title":"Primary Ciliary Dyskinesia in the Genomics Age","volume":"8","author":"Lucas","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.prrv.2015.07.017","article-title":"Diagnostic Methods in Primary Ciliary Dyskinesia","volume":"18","author":"Lucas","year":"2016","journal-title":"Paediatric Respir. Rev."},{"key":"B14","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1471-2466-3-4","article-title":"Primary Ciliary Dyskinesia (Siewert's\/Kartagener's Syndrome): Respiratory Symptoms and Psycho-Social Impact","volume":"3","author":"McManus","year":"2003","journal-title":"BMC Pulm. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/s12687-011-0071-z","article-title":"Carrier Screening in Preconception Consultation in Primary Care","volume":"3","author":"Metcalfe","year":"2012","journal-title":"J. Community Genet."},{"key":"B16","doi-asserted-by":"publisher","first-page":"135","DOI":"10.3389\/fped.2017.00135","article-title":"Primary Ciliary Dyskinesia: An Update on Clinical Aspects, Genetics, Diagnosis, and Future Treatment Strategies","volume":"5","author":"Mirra","year":"2017","journal-title":"Front. Pediatr."},{"key":"B17","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/s1097-2765(00)80197-5","article-title":"Abnormal Nodal Flow Precedes Situs Inversus in Iv and Inv Mice","volume":"4","author":"Okada","year":"1999","journal-title":"Mol. Cel"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1183\/09031936.00186209","article-title":"New DNAH11 Mutations in Primary Ciliary Dyskinesia with normal Axonemal Ultrastructure","volume":"35","author":"Pifferi","year":"2010","journal-title":"Eur. Respir. J."},{"key":"B19","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and Guidelines for the Interpretation of Sequence Variants: a Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"170023","DOI":"10.1183\/16000617.0023-2017","article-title":"Clinical Care for Primary Ciliary Dyskinesia: Current Challenges and Future Directions","volume":"26","author":"Rubbo","year":"2017","journal-title":"Eur. Respir. Rev."},{"key":"B21","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1002\/ppul.23304","article-title":"Diagnosis, Monitoring, and Treatment of Primary Ciliary Dyskinesia: PCD Foundation Consensus Recommendations Based on State of the Art Review","volume":"51","author":"Shapiro","year":"2016","journal-title":"Pediatr. Pulmonol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1701809","DOI":"10.1183\/13993003.01809-2017","article-title":"Primary Ciliary Dyskinesia with normal Ultrastructure: Three-Dimensional Tomography Detects Absence of DNAH11","volume":"51","author":"Shoemark","year":"2018","journal-title":"Eur. Respir. J."},{"key":"B23","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1183\/09031936.05.00015205","article-title":"Nasal NO: normal Values in Children Age 6 through to 17 Years","volume":"26","author":"Struben","year":"2005","journal-title":"Eur. Respir. J."},{"key":"B24","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1038\/40140","article-title":"Mutation of an Axonemal Dynein Affects Left-Right Asymmetry in Inversus Viscerum Mice","volume":"389","author":"Supp","year":"1997","journal-title":"Nature"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e0252786","DOI":"10.1371\/journal.pone.0252786","article-title":"DNAH11 Compound Heterozygous Variants Cause Heterotaxy and Congenital Heart Disease","volume":"16","author":"Xia","year":"2021","journal-title":"PLoS One"},{"key":"B26","doi-asserted-by":"publisher","first-page":"749","DOI":"10.3389\/fgene.2019.00749","article-title":"Identification of Pathogenic Mutations and Investigation of the NOTCH Pathway Activation in Kartagener Syndrome","volume":"10","author":"Yue","year":"2019","journal-title":"Front. Genet."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.814511\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T10:21:40Z","timestamp":1646043700000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.814511\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,28]]},"references-count":26,"alternative-id":["10.3389\/fgene.2022.814511"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.814511","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,28]]},"article-number":"814511"}}