{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T10:12:04Z","timestamp":1783505524045,"version":"3.55.0"},"reference-count":19,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T00:00:00Z","timestamp":1651449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UPRMSC Hispanics-In-Research Capability (HiREC)","award":["S21MD001830"],"award-info":[{"award-number":["S21MD001830"]}]},{"name":"UPRMSC Hispanics-In-Research Capability (HiREC)","award":["HCTRECD R25MD007607"],"award-info":[{"award-number":["HCTRECD R25MD007607"]}]},{"name":"UPRMSC Hispanics-In-Research Capability (HiREC)","award":["D34HP24463"],"award-info":[{"award-number":["D34HP24463"]}]},{"name":"UPRMSC Hispanics-In-Research Capability (HiREC)","award":["PRSTRT: 2022-00012A"],"award-info":[{"award-number":["PRSTRT: 2022-00012A"]}]},{"name":"NIH National Institute of Minority Health and Health Disparities","award":["S21MD001830"],"award-info":[{"award-number":["S21MD001830"]}]},{"name":"NIH National Institute of Minority Health and Health Disparities","award":["HCTRECD R25MD007607"],"award-info":[{"award-number":["HCTRECD R25MD007607"]}]},{"name":"NIH National Institute of Minority Health and Health Disparities","award":["D34HP24463"],"award-info":[{"award-number":["D34HP24463"]}]},{"name":"NIH National Institute of Minority Health and Health Disparities","award":["PRSTRT: 2022-00012A"],"award-info":[{"award-number":["PRSTRT: 2022-00012A"]}]},{"name":"The National Institute of Health","award":["S21MD001830"],"award-info":[{"award-number":["S21MD001830"]}]},{"name":"The National Institute of Health","award":["HCTRECD R25MD007607"],"award-info":[{"award-number":["HCTRECD R25MD007607"]}]},{"name":"The National Institute of Health","award":["D34HP24463"],"award-info":[{"award-number":["D34HP24463"]}]},{"name":"The National Institute of Health","award":["PRSTRT: 2022-00012A"],"award-info":[{"award-number":["PRSTRT: 2022-00012A"]}]},{"name":"Hispanic Center of Excellence, University of Puerto Rico School of Medicine","award":["S21MD001830"],"award-info":[{"award-number":["S21MD001830"]}]},{"name":"Hispanic Center of Excellence, University of Puerto Rico School of Medicine","award":["HCTRECD R25MD007607"],"award-info":[{"award-number":["HCTRECD R25MD007607"]}]},{"name":"Hispanic Center of Excellence, University of Puerto Rico School of Medicine","award":["D34HP24463"],"award-info":[{"award-number":["D34HP24463"]}]},{"name":"Hispanic Center of Excellence, University of Puerto Rico School of Medicine","award":["PRSTRT: 2022-00012A"],"award-info":[{"award-number":["PRSTRT: 2022-00012A"]}]},{"name":"The Puerto Rico Science, Technology, and Research Trust","award":["S21MD001830"],"award-info":[{"award-number":["S21MD001830"]}]},{"name":"The Puerto Rico Science, Technology, and Research Trust","award":["HCTRECD R25MD007607"],"award-info":[{"award-number":["HCTRECD R25MD007607"]}]},{"name":"The Puerto Rico Science, Technology, and Research Trust","award":["D34HP24463"],"award-info":[{"award-number":["D34HP24463"]}]},{"name":"The Puerto Rico Science, Technology, and Research Trust","award":["PRSTRT: 2022-00012A"],"award-info":[{"award-number":["PRSTRT: 2022-00012A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Primary ciliary dyskinesia (PCD) has been linked to more than 50 genes that cause a spectrum of clinical symptoms, including newborn respiratory distress, sinopulmonary infections, and laterality abnormalities. Although the RSPH4A (c.921+3_6delAAGT) pathogenic variant has been related to Hispanic groups with Puerto Rican ancestry, it is uncertain how frequently other PCD-implicated genes are present on the island. A retrospective chart review of n = 127 genetic reports from Puerto Rican subjects who underwent genetic screening for PCD variants was conducted from 2018 to 2022. Of 127 subjects, 29.1% subjects presented PCD pathogenic variants, and 13.4% were homozygous for the RSPH4A (c.921+3_6delAAGT) founder mutation. The most common pathogenic variants were in RSPH4A and ZMYND10 genes. A description of the frequency and geographic distribution of implicated PCD pathogenic variants in Puerto Rico is presented. Our findings reconfirm that the presence of PCD in Puerto Rico is predominantly due to a founder pathogenic variant in the RSPH4A (c.921+3_6delAAGT) splice site. Understanding the frequency of PCD genetic variants in Puerto Rico is essential to map a future genotype-phenotype PCD spectrum in Puerto Rican Hispanics with a heterogeneous ancestry.<\/jats:p>","DOI":"10.3390\/diagnostics12051127","type":"journal-article","created":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T07:08:58Z","timestamp":1651475338000},"page":"1127","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The Genetics of Primary Ciliary Dyskinesia in Puerto Rico"],"prefix":"10.3390","volume":"12","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\u2013Anatomy and Neuroanatomy, University of Puerto Rico, Medical Sciences Campus, San Juan, PR 00921, USA"},{"name":"Department of Pediatrics, Ponce Health Science University, Ponce, PR 00716, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Mu\u00f1iz-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Natural Science, University of Puerto Rico, Cayey Campus, Cayey, PR 00736, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Alvarado-Huerta","sequence":"additional","affiliation":[{"name":"Department of Pediatrics\u2013Anatomy and Neuroanatomy, University of Puerto Rico, Medical Sciences Campus, San Juan, PR 00921, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4441-6780","authenticated-orcid":false,"given":"Jes\u00fas M.","family":"Mel\u00e9ndez-Monta\u00f1ez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ponce Health Science University, Ponce, PR 00716, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaldo J.","family":"Santos-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ponce Health Science University, Ponce, PR 00716, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo A.","family":"Mosquera","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,2]]},"reference":[{"key":"ref_1","unstructured":"Zariwala, M.A., Knowles, M.R., and Leigh, M.W. (1993). Primary Ciliary Dyskinesia. GeneReviews((R)), University of Washington."},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1513\/AnnalsATS.201810-693CME","article-title":"Summary for Clinicians: Diagnosis of Primary Ciliary Dyskinesia","volume":"16","author":"Griffiths","year":"2019","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"O\u2019Connor, M.G., Horani, A., and Shapiro, A.J. (2021). Progress in Diagnosing Primary Ciliary Dyskinesia: The North American Perspective. Diagnostics, 11.","DOI":"10.3390\/diagnostics11071278"},{"key":"ref_5","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. Care Med."},{"key":"ref_6","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_7","doi-asserted-by":"crossref","unstructured":"De Jes\u00fas-Rojas, W., Reyes-De Jes\u00fas, D., and Mosquera, R.A. (2021). Primary Ciliary Dyskinesia Diagnostic Challenges: Understanding the Clinical Phenotype of the Puerto Rican. Diagnostics, 11.","DOI":"10.3390\/diagnostics11020281"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1002\/humu.22371","article-title":"Founder mutation in RSPH4A identified in patients of Hispanic descent with primary ciliary dyskinesia","volume":"34","author":"Daniels","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Via, M., Gignoux, C.R., Roth, L.A., Fejerman, L., Galanter, J., Choudhry, S., Toro-Labrador, G., Viera-Vera, J., Oleksyk, T.K., and Beckman, K. (2011). History shaped the geographic distribution of genomic admixture on the island of Puerto Rico. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016513"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1055\/s-0040-1708088","article-title":"Hermansky-Pudlak Syndrome","volume":"41","author":"Young","year":"2020","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"ref_11","first-page":"e17673","article-title":"Primary Ciliary Dyskinesia: Ancestral Haplotypes Analysis of the RSPH4A Founder Mutation in Puerto Rico","volume":"13","author":"Nieves","year":"2021","journal-title":"Cureus"},{"key":"ref_12","first-page":"325","article-title":"How insignificant are genetic variants of unknown significance in Primary Ciliary Dyskinesia?","volume":"56","author":"Bhatt","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"57","DOI":"10.5409\/wjcp.v5.i1.57","article-title":"Clinical spectrum of primary ciliary dyskinesia in childhood","volume":"5","author":"Fretzayas","year":"2016","journal-title":"World J. Clin. Pediatr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1038\/gim.2017.37","article-title":"Sherloc: A comprehensive refinement of the ACMG-AMP variant classification criteria","volume":"19","author":"Nykamp","year":"2017","journal-title":"Genet. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ccm.2021.11.008","article-title":"Diagnosis of Primary Ciliary Dyskinesia","volume":"43","author":"Goutaki","year":"2022","journal-title":"Clin. Chest Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"bcr-2018-224964","DOI":"10.1136\/bcr-2018-224964","article-title":"Severe disease due to CCDC40 gene variants and the perils of late diagnosis in primary ciliary dyskinesia","volume":"2018","author":"Ghandourah","year":"2018","journal-title":"BMJ Case Rep."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Moreno-Estrada, A., Gravel, S., Zakharia, F., McCauley, J.L., Byrnes, J.K., Gignoux, C.R., Ortiz-Tello, P.A., Mart\u00ednez, R.J., Hedges, D.J., and Morris, R.W. (2013). Reconstructing the population genetic history of the Caribbean. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003925"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.ajhg.2020.06.004","article-title":"Bi-allelic DNAH8 Variants Lead to Multiple Morphological Abnormalities of the Sperm Flagella and Primary Male Infertility","volume":"107","author":"Liu","year":"2020","journal-title":"Am. J. Hum. Genet."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/5\/1127\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:05:40Z","timestamp":1760137540000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/5\/1127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,2]]},"references-count":19,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["diagnostics12051127"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics12051127","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,2]]}}}