{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:30:49Z","timestamp":1790994649745,"version":"4.1.0"},"reference-count":18,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:00:00Z","timestamp":1613001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Health and Human Services, Health Resources and Services Administration, Bureau of Health Workforce.","award":["D34HP24463"],"award-info":[{"award-number":["D34HP24463"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Primary ciliary dyskinesia (PCD) is a rare, heterogeneous ciliopathy resulting in chronic oto-sino-pulmonary disease, bronchiectasis, newborn respiratory distress, and laterality defects. PCD diagnosis can be achieved by following diagnostic algorithms that include electron microscopy, genetics, and ancillary testing. Genetic mutations in more than 45 genes, including RSPH4A, can lead to PCD. RSPH4A mutations located on chromosome six, affect radial spokes and results in central complex apparatus abnormalities. The RSPH4A [c.921 + 3_6delAAGT] founder mutation was described as one cause of PCD without laterality defects in Puerto Rico. Additionally, there are further diagnostic challenges present in the Puerto Rican population to diagnose PCD. We describe the demographics, clinical features, and RSPH4A genetic variants in 13 patients with clinical PCD affecting 11 Puerto Ricans from unrelated families.<\/jats:p>","DOI":"10.3390\/diagnostics11020281","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T18:45:00Z","timestamp":1613155500000},"page":"281","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Primary Ciliary Dyskinesia Diagnostic Challenges: Understanding the Clinical Phenotype of the Puerto Rican RSPH4A Founder Mutation"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6133-3517","authenticated-orcid":false,"given":"Wilfredo","family":"De Jes\u00fas-Rojas","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Medical Sciences Campus, School of Medicine, University of Puerto Rico, San Juan 00921, Puerto Rico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalilah","family":"Reyes-De Jes\u00fas","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical Sciences Campus, School of Medicine, University of Puerto Rico, San Juan 00921, Puerto Rico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo A.","family":"Mosquera","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Houston Medical School, University of Texas Health Science Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1164\/rccm.201301-0059CI","article-title":"Primary Ciliary Dyskinesia. Recent Advances in Diagnostics, Genetics, and Characterization of Clinical Disease","volume":"188","author":"Knowles","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_2","first-page":"51","article-title":"Primary ciliary dyskinesia (PCD): A genetic disorder of motile cilia","volume":"4","author":"Leigh","year":"2019","journal-title":"Transl. Sci. Rare Dis."},{"key":"ref_3","unstructured":"Zariwala, M.A., Knowles, M.R., and Leigh, M.W. (1993). Primary Ciliary Dyskinesia, GeneReviews."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e24","DOI":"10.1164\/rccm.201805-0819ST","article-title":"Diagnosis of Primary Ciliary Dyskinesia. An Official American Thoracic Society Clinical Practice Guideline","volume":"197","author":"Shapiro","year":"2018","journal-title":"Am. J. Respir. Crit. 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Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.ajhg.2009.01.011","article-title":"Mutations in Radial Spoke Head Protein Genes RSPH9 and RSPH4A Cause Primary Ciliary Dyskinesia with Central-Microtubular-Pair Abnormalities","volume":"84","author":"Castleman","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"a028241","DOI":"10.1101\/cshperspect.a028241","article-title":"Cilia and Mucociliary Clearance","volume":"9","author":"Ostrowski","year":"2017","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1378\/chest.13-1704","article-title":"Laterality Defects Other Than Situs Inversus Totalis in Primary Ciliary Dyskinesia","volume":"146","author":"Shapiro","year":"2014","journal-title":"Chest"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Nonaka, S., Yoshiba, S., Watanabe, D., Ikeuchi, S., Goto, T., Marshall, W.F., and Hamada, H. (2005). De Novo Formation of Left\u2013Right Asymmetry by Posterior Tilt of Nodal Cilia. PLoS Biol., 3.","DOI":"10.1371\/journal.pbio.0030268"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1164\/rccm.200306-782OC","article-title":"Central Microtubular Agenesis Causing Primary Ciliary Dyskinesia","volume":"169","author":"Stannard","year":"2004","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1002\/humu.22371","article-title":"Founder Mutation inRSPH4AIdentified in Patients of Hispanic Descent with Primary Ciliary Dyskinesia","volume":"34","author":"Daniels","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1183\/09031936.05.00034505","article-title":"General considerations for lung function testing","volume":"26","author":"Miller","year":"2005","journal-title":"Eur. Respir. J."},{"key":"ref_16","first-page":"1","article-title":"Gene Mutations in Primary Ciliary Dyskinesia Related to Otitis Media","volume":"14","author":"Roig","year":"2014","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1001\/archoto.2010.183","article-title":"Otologic Features in Children With Primary Ciliary Dyskinesia","volume":"136","author":"Escabasse","year":"2010","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"a028191","DOI":"10.1101\/cshperspect.a028191","article-title":"Ciliopathies","volume":"9","author":"Braun","year":"2016","journal-title":"Cold Spring Harb. Perspect. 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