{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:34:54Z","timestamp":1792226094734,"version":"4.4.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,3,1]],"date-time":"2020-03-01T00:00:00Z","timestamp":1583020800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Primary ciliary dyskinesia (PCD) is a genetically heterogeneous chronic destructive airway disease. PCD is traditionally diagnosed by nasal nitric oxide measurement, analysis of ciliary beating, transmission electron microscopy (TEM), and\/or genetic testing. In most genetic PCD variants, laterality defects can occur. However, it is difficult to establish a diagnosis in individuals with PCD and central pair (CP) defects, and alternative strategies are required because of very subtle ciliary beating abnormalities, a normal ciliary ultrastructure, and normal situs composition. Mutations in HYDIN are known to cause CP defects, but the genetic analysis of HYDIN variants is confounded by the pseudogene HYDIN2, which is almost identical in terms of intron\/exon structure. We have previously shown that several types of PCD can be diagnosed via immunofluorescence (IF) microscopy analyses. Here, using IF microscopy, we demonstrated that in individuals with PCD and CP defects, the CP-associated protein SPEF2 is absent in HYDIN-mutant cells, revealing its dependence on functional HYDIN. Next, we performed IF analyses of SPEF2 in respiratory cells from 189 individuals with suspected PCD and situs solitus. Forty-one of the 189 individuals had undetectable SPEF2 and were subjected to a genetic analysis, which revealed one novel loss-of-function mutation in SPEF2 and three reported and 13 novel HYDIN mutations in 15 individuals. The remaining 25 individuals are good candidates for new, as-yet uncharacterized PCD variants that affect the CP apparatus. SPEF2 mutations have been associated with male infertility but have not previously been identified to cause PCD. We identified a mutation of SPEF2 that is causative for PCD with a CP defect. We conclude that SPEF2 IF analyses can facilitate the detection of CP defects and evaluation of the pathogenicity of HYDIN variants, thus aiding the molecular diagnosis of CP defects.<\/jats:p>","DOI":"10.1165\/rcmb.2019-0086oc","type":"journal-article","created":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T16:52:23Z","timestamp":1569257543000},"page":"382-396","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":77,"title":["<i>SPEF2-<\/i>\n                    and\n                    <i>HYDIN<\/i>\n                    -Mutant Cilia Lack the Central Pair\u2013associated Protein SPEF2, Aiding Primary Ciliary Dyskinesia Diagnostics"],"prefix":"10.1093","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8303-100X","authenticated-orcid":false,"given":"Sandra","family":"Cindri\u0107","sequence":"first","affiliation":[{"name":"Department of General Pediatrics, University Children\u2019s Hospital Muenster, Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard W.","family":"Dougherty","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, University Children\u2019s Hospital Muenster, Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Olbrich","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, University Children\u2019s Hospital Muenster, Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rim","family":"Hjeij","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, University Children\u2019s Hospital Muenster, Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niki Tomas","family":"Loges","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, University Children\u2019s Hospital Muenster, Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israel","family":"Amirav","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C.","family":"Philipsen","sequence":"additional","affiliation":[{"name":"Danish PCD Centre, ERN Accredited, Pediatric Pulmonary Service, Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"June K.","family":"Marthin","sequence":"additional","affiliation":[{"name":"Danish PCD Centre, ERN Accredited, Pediatric Pulmonary Service, Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim G.","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Danish PCD Centre, ERN Accredited, Pediatric Pulmonary Service, Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivagurunathan","family":"Sutharsan","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, Ruhrlandklinik, Universit\u00e4tsmedizin Essen, Essen, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Raidt","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, University Children\u2019s Hospital Muenster, Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudius","family":"Werner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, HELIOS Hospital Schwerin, Schwerin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Pennekamp","sequence":"additional","affiliation":[{"name":"Department 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