{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:31:32Z","timestamp":1787499092200,"version":"build-2736575974"},"reference-count":19,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T00:00:00Z","timestamp":1672444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Non-Profit Organization aimed at supporting community medicine research in Nagasaki","award":["19K09886"],"award-info":[{"award-number":["19K09886"]}]},{"name":"Non-Profit Organization aimed at supporting community medicine research in Nagasaki","award":["22K09665"],"award-info":[{"award-number":["22K09665"]}]},{"name":"JSPS Grants-in-Aid for Scientific Research (C)","award":["19K09886"],"award-info":[{"award-number":["19K09886"]}]},{"name":"JSPS Grants-in-Aid for Scientific Research (C)","award":["22K09665"],"award-info":[{"award-number":["22K09665"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Primary ciliary dyskinesia (PCD) is a genetic and congenital disease associated with an abnormal ciliary ultrastructure and function and is estimated to affect 1 in 15,000\u201320,000 individuals. A PCD diagnosis can be achieved by genotyping. Here, we performed whole-exome analysis for the diagnosis of PCD and described the detailed clinical characteristics of the case. A 39-year-old Japanese woman with sinusitis and bronchiectasis without situs inversus had had upper and lower respiratory symptoms since childhood and had received long-term macrolide therapy without an accurate diagnosis. A moderate deterioration of cilia function was observed by high-speed video microscopy analysis; additionally, the number of cells with moving cilia was fewer than that in patients without PCD. Electron microscopy revealed no apparent structural abnormalities. We performed whole-exome analysis and identified novel biallelic variants of SPEF2 in the homozygous state (c.1860_1861insCT). We confirmed the absence of SPEF2 protein expression in the cilia of the nasal mucosa using fluorescent immunostaining. Accordingly, she was diagnosed as having PCD with the SPEF2 variant. The present case suggests that the deterioration of cilia function is moderate, the number of respiratory cells with moving cilia might be reduced, and the respiratory condition could be severe in patients with PCD with the SPEF2 variant.<\/jats:p>","DOI":"10.3390\/jcm12010317","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T03:00:59Z","timestamp":1672628459000},"page":"317","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Novel SPEF2 Variant in a Japanese Patient with Primary Ciliary Dyskinesia: A Case Report and Literature Review"],"prefix":"10.3390","volume":"12","author":[{"given":"Mayako","family":"Mori","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8338-0608","authenticated-orcid":false,"given":"Takashi","family":"Kido","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7577-476X","authenticated-orcid":false,"given":"Noriho","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mutsumi","family":"Ozasa","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"},{"name":"Department of Pathology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8520, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumiko","family":"Kido","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuko","family":"Noguchi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"},{"name":"J-One, Nagasaki 852-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takatomo","family":"Tokito","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Okuno","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Yura","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuko","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Ishimoto","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Suematsu","sequence":"additional","affiliation":[{"name":"Central Electron Microscope Laboratory, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8838-7403","authenticated-orcid":false,"given":"Yasushi","family":"Obase","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5024-0614","authenticated-orcid":false,"given":"Yoshimasa","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Center for Medical Innovation, Nagasaki University, Nagasaki 852-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Izumikawa","sequence":"additional","affiliation":[{"name":"Department of Infection Control and Education Center, Nagasaki University Hospital, Nagasaki 852-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6855-6425","authenticated-orcid":false,"given":"Kazuhiko","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Graduate School of Medicine, Mie University, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Mukae","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1164\/rccm.200303-365OC","article-title":"Primary ciliary dyskinesia: Diagnostic and phenotypic features","volume":"169","author":"Noone","year":"2004","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.prrv.2008.10.001","article-title":"Primary ciliary dyskinesia: When to suspect the diagnosis and how to confirm it","volume":"10","author":"Hogg","year":"2009","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S2213-2600(21)00453-7","article-title":"The global prevalence and ethnic heterogeneity of primary ciliary dyskinesia gene variants: A genetic database analysis","volume":"10","author":"Hannah","year":"2022","journal-title":"Lancet Respir. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s00405-010-1341-9","article-title":"ENT manifestations in patients with primary ciliary dyskinesia: Prevalence and significance of otorhinolaryngologic co-morbidities","volume":"268","author":"Sommer","year":"2011","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1183\/13993003.02018-2015","article-title":"Diagnosing primary ciliary dyskinesia: An international patient perspective","volume":"48","author":"Behan","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1513\/AnnalsATS.201511-748OC","article-title":"Clinical Features and Associated Likelihood of Primary Ciliary Dyskinesia in Children and Adolescents","volume":"13","author":"Leigh","year":"2016","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1164\/rccm.201409-1672OC","article-title":"Clinical features of childhood primary ciliary dyskinesia by genotype and ultrastructural phenotype","volume":"191","author":"Davis","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1601090","DOI":"10.1183\/13993003.01090-2016","article-title":"European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia","volume":"49","author":"Lucas","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1183\/09031936.00052014","article-title":"Ciliary beat pattern and frequency in genetic variants of primary ciliary dyskinesia","volume":"44","author":"Raidt","year":"2014","journal-title":"Eur. Respir. J."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Hirst, R.A., Jackson, C.L., Coles, J.L., Williams, G., Rutman, A., Goggin, P.M., Adam, E.C., Page, A., Evans, H.J., and Lackie, P.M. (2014). Culture of primary ciliary dyskinesia epithelial cells at air-liquid interface can alter ciliary phenotype but remains a robust and informative diagnostic aid. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0089675"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1137","DOI":"10.1002\/mgg3.1137","article-title":"Copy number variation in DRC1 is the major cause of primary ciliary dyskinesia in the Japanese population","volume":"8","author":"Takeuchi","year":"2020","journal-title":"Mol. Genet. Genomic Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1165\/rcmb.2019-0086OC","article-title":"SPEF2- and HYDIN-mutant cilia lack the central pair-associated protein SPEF2, aiding primary ciliary dyskinesia diagnostics","volume":"62","author":"Dougherty","year":"2020","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s00439-020-02110-0","article-title":"Novel mutations in SPEF2 causing different defects between flagella and cilia bridge: The phenotypic link between MMAF and PCD","volume":"139","author":"Tu","year":"2020","journal-title":"Hum. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1136\/jmedgenet-2019-106011","article-title":"Homozygous mutations in SPEF2 induce multiple morphological abnormalities of the sperm flagella and male infertility","volume":"57","author":"Liu","year":"2020","journal-title":"J. Med. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1165\/ajrcmb.20.4.3496","article-title":"Cloning and characterization of KPL2, a novel gene induced during ciliogenesis of tracheal epithelial cells","volume":"20","author":"Ostrowski","year":"1999","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"359","DOI":"10.4103\/aja202154","article-title":"Sperm flagellar 2 (SPEF2) is essential for sperm flagellar assembly in humans","volume":"24","author":"Li","year":"2022","journal-title":"Asian J. Andro."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/S0091-6749(03)01799-8","article-title":"Ciliary beat pattern is associated with specific ultrastructural defects in primary ciliary dyskinesia","volume":"112","author":"Chilvers","year":"2003","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.2214\/AJR.06.0965","article-title":"High-resolution CT of patients with primary ciliary dyskinesia","volume":"188","author":"Kennedy","year":"2007","journal-title":"AJR Am. J. Roentgenol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.2169\/internalmedicine.51.6617","article-title":"Two cases of primary ciliary dyskinesia with different responses to macrolide treatment","volume":"51","author":"Kido","year":"2012","journal-title":"Intern Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/1\/317\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:49:00Z","timestamp":1760147340000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/1\/317"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,31]]},"references-count":19,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["jcm12010317"],"URL":"https:\/\/doi.org\/10.3390\/jcm12010317","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,31]]}}}