{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T05:26:51Z","timestamp":1793424411683,"version":"4.5.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T00:00:00Z","timestamp":1684368000000},"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>Objectives:<\/jats:bold> Cystic fibrosis (CF) is the most prevalent autosomal recessive disorder among Caucasians. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause this pathology. We, therefore, aimed to describe the CFTR mutations and their geographical distribution in Iran.<\/jats:p><jats:p><jats:bold>Method:<\/jats:bold> The mutation spectrum for 87 families from all Iranian ethnicities was collected using ARMS PCR, Sanger sequencing, and MLPA.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Mutations were identified in 95.8% of cases. This dataset revealed that the most frequent mutations in the Iranian population were F508del, c.1000C&amp;gt;T, c.1397C&amp;gt;G, c.1911delG, and c.1393-1G&amp;gt;A. In addition, we found weak evidence for Turkey being the possible geographical pathway for introducing CFTR mutations into Iran by mapping the frequency of CFTR mutations.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Our descriptive results will facilitate the genetic detection and prenatal diagnosis of cystic fibrosis within the Iranian population.<\/jats:p>","DOI":"10.3389\/fgene.2023.1140034","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T17:18:46Z","timestamp":1684430326000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Genetic attributes of Iranian cystic fibrosis patients: the diagnostic efficiency of CFTR mutations in over a decade"],"prefix":"10.3389","volume":"14","author":[{"given":"Amin","family":"Hosseini Nami","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahboubeh","family":"Kabiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Zafarghandi Motlagh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Shirzadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Negar","family":"Fakhari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Karimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamideh","family":"Bagherian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojdeh","family":"Jamali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahrzad","family":"Younesikhah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Shadman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razie","family":"Zeinali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirous","family":"Zeinali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.jcf.2007.06.001","article-title":"Analysis of the CFTR gene in Iranian cystic fibrosis patients: Identification of eight novel mutations","volume":"7","author":"Alibakhshi","year":"2008","journal-title":"J. Cyst. Fibros."},{"key":"B2","doi-asserted-by":"publisher","first-page":"556","DOI":"10.3389\/fimmu.2020.00556","article-title":"KIR variation in Iranians combines high haplotype and allotype diversity with an abundance of functional inhibitory receptors","volume":"11","author":"Alicata","year":"2020","journal-title":"Front. Immunol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1007\/BF03260073","article-title":"Application of multiplex ARMS and SSCP\/HD analysis in molecular diagnosis of cystic fibrosis in Indian patients","volume":"9","author":"Ashavaid","year":"2005","journal-title":"Mol. Diagn"},{"key":"B4","doi-asserted-by":"publisher","first-page":"15","DOI":"10.5144\/0256-4947.2020.15","article-title":"Genotype patterns for mutations of the cystic fibrosis transmembrane conductance regulator gene: A retrospective descriptive study from Saudi Arabia","volume":"40","author":"Banjar","year":"2020","journal-title":"Ann. Saudi Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1002\/humu.10041","article-title":"Cystic fibrosis: A worldwide analysis of CFTR mutations\u2013correlation with incidence data and application to screening","volume":"19","author":"Bobadilla","year":"2002","journal-title":"Hum. Mutat."},{"key":"B6","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.jcf.2008.03.009","article-title":"Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice","volume":"7","author":"Castellani","year":"2008","journal-title":"J. Cyst. Fibros."},{"key":"B7","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1136\/jmg.31.7.541","article-title":"Mutation analysis in 600 French cystic fibrosis patients","volume":"31","author":"Chevalier-Porst","year":"1994","journal-title":"J. Med. Genet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.jcf.2008.09.004","article-title":"Common mutations in Cuban cystic fibrosis patients","volume":"8","author":"Collazo","year":"2009","journal-title":"J. Cyst. Fibros."},{"key":"B9","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1146\/annurev.genom.6.080604.162254","article-title":"Modifier genetics: Cystic fibrosis","volume":"6","author":"Cutting","year":"2005","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.prrv.2020.07.004","article-title":"Cystic fibrosis in low and middle-income countries (lmic): A view from four different regions of the world","volume":"38","author":"da Silva Filho","year":"2021","journal-title":"Paediatr. Respir. Rev."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1984","DOI":"10.1016\/S0140-6736(18)33197-0","article-title":"Iran in transition","volume":"393","author":"Danaei","year":"2019","journal-title":"Lancet"},{"key":"B12","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1002\/(SICI)1098-1004(200001)15:1<7::AID-HUMU4>3.0.CO;2-N","article-title":"Mutation nomenclature extensions and suggestions to describe complex mutations: A discussion","volume":"15","author":"den Dunnen","year":"2000","journal-title":"Hum. Mutat."},{"key":"B13","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/j.jcf.2004.04.008","article-title":"Sarda PHigh heterogeneity of CFTR mutations and unexpected low incidence of cystic fibrosis in the Mediterranean France","volume":"3","author":"des Georges","year":"2004","journal-title":"J. Cyst. Fibros."},{"key":"B14","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1006\/geno.1993.1127","article-title":"Four novel cystic fibrosis mutations in splice junction sequences affecting the CFTR nucleotide binding folds","volume":"15","author":"D\u00f6rk","year":"1993","journal-title":"Genomics"},{"key":"B15","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/s10038-020-00859-w","article-title":"Analysis of rearrangements of the CFTR gene in patients from Turkey with CFTR-related disorders: Frequent exon 2 deletion","volume":"66","author":"Duz","year":"2021","journal-title":"J. Hum. Genet."},{"key":"B16","doi-asserted-by":"publisher","first-page":"119","DOI":"10.2353\/jmoldx.2006.050063","article-title":"A haplotype framework for cystic fibrosis mutations in Iran","volume":"8","author":"Elahi","year":"2006","journal-title":"J. Mol. Diagn"},{"key":"B17","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1093\/tropej\/48.6.348","article-title":"Cystic fibrosis transmembrane regulator gene mutations in Bahrain","volume":"48","author":"Eskandarani","year":"2002","journal-title":"J. Trop. Pediatr."},{"key":"B18","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.gene.2015.03.056","article-title":"Mutation and new polymorphisms insight in introns 11 to 14a of CFTR gene of northern Iranian cystic fibrosis patients","volume":"564","author":"Esmaeili Dooki","year":"2015","journal-title":"Gene"},{"key":"B19","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1002\/(SICI)1098-1004(1997)10:2<135::AID-HUMU6>3.0.CO;2-J","article-title":"Geographic distribution and regional origin of 272 cystic fibrosis mutations in European populations. The Biomed CF Mutation Analysis Consortium","volume":"10","author":"Estivill","year":"1997","journal-title":"Hum. Mutat."},{"key":"B20","unstructured":"ECFS patient registry annual reports2017"},{"key":"B21","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.jcf.2008.03.007","article-title":"The prevalence of cystic fibrosis in the European Union","volume":"7","author":"Farrell","year":"2008","journal-title":"J. Cyst. Fibros."},{"key":"B22","doi-asserted-by":"publisher","first-page":"S4-S15.e1","DOI":"10.1016\/j.jpeds.2016.09.064","article-title":"Diagnosis of cystic fibrosis: Consensus guidelines from the cystic fibrosis foundation","author":"Farrell","year":"2017","journal-title":"J. Pediatr."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1968","DOI":"10.1002\/humu.23880","article-title":"Iranome: A catalog of genomic variations in the Iranian population","volume":"40","author":"Fattahi","year":"2019","journal-title":"Hum. Mutat."},{"key":"B24","first-page":"120","article-title":"A comparative evaluation of four DNA extraction protocols from whole blood sample","volume":"62","author":"Ghaheri","year":"2016","journal-title":"Cell Mol. Biol. (Noisy-le-grand)"},{"key":"B25","doi-asserted-by":"publisher","first-page":"3513","DOI":"10.3390\/ijms23073513","article-title":"The effect of CFTR modulators on airway infection in cystic fibrosis","volume":"23","author":"Harvey","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"398","DOI":"10.52547\/ibj.3713","article-title":"Reporting two novel mutations in two Iranian families with cystic fibrosis, molecular and bioinformatic analysis","volume":"26","author":"Hosseini Nami","year":"2022","journal-title":"Iran. Biomed. J."},{"key":"B27","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s12881-019-0815-x","article-title":"Phenotypic spectrum and genetic heterogeneity of cystic fibrosis in Sri Lanka","volume":"20","author":"Indika","year":"2019","journal-title":"BMC Med. Genet."},{"key":"B28","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.jcf.2017.11.013","article-title":"Epidemiology of CF: How registries can be used to advance our understanding of the CF population","volume":"17","author":"Jackson","year":"2018","journal-title":"J. Cyst. Fibros."},{"key":"B29","first-page":"3","article-title":"CFTR mutation analysis in western Iran: Identification of two novel mutations","volume":"19","author":"Karimi","year":"2018","journal-title":"J. Reprod. Infertil."},{"key":"B30","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.jcf.2010.10.002","article-title":"Cystic fibrosis in Chilean patients: Analysis of 36 common CFTR gene mutations","volume":"10","author":"Lay-Son","year":"2011","journal-title":"J. Cyst. Fibros."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1662","DOI":"10.3389\/fphar.2019.01662","article-title":"CFTR modulators: The changing face of cystic fibrosis in the era of precision medicine","volume":"10","author":"Lopes-Pacheco","year":"2019","journal-title":"Front. Pharmacol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/jhg.2010.96","article-title":"Genetic causes of nonsyndromic hearing loss in Iran in comparison with other populations","volume":"55","author":"Mahdieh","year":"2010","journal-title":"J. Hum. Genet."},{"key":"B33","first-page":"917","article-title":"Analysis of CFTR gene mutations in children with cystic fibrosis, first report from north-East of Iran","volume":"16","author":"Mehdizadeh Hakkak","year":"2013","journal-title":"Iran. J. Basic Med. Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"e1008385","DOI":"10.1371\/journal.pgen.1008385","article-title":"Distinct genetic variation and heterogeneity of the Iranian population","volume":"15","author":"Mehrjoo","year":"2019","journal-title":"PLoS Genet."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1073\/pnas.1914912117","article-title":"Cystic fibrosis carriers are at increased risk for a wide range of cystic fibrosis-related conditions","volume":"117","author":"Miller","year":"2020","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1093\/nar\/16.3.1215","article-title":"A simple salting out procedure for extracting DNA from human nucleated cells","volume":"16","author":"Miller","year":"1988","journal-title":"Nucleic Acids Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"86","DOI":"10.18502\/ijph.v49i1.3055","article-title":"Health status in the islamic republic of Iran, Middle East and north africa countries: Implications for global health","volume":"49","author":"Mirzaei","year":"2020","journal-title":"Iran. J. Public Health"},{"key":"B38","first-page":"890","article-title":"Independent origins of cystic fibrosis mutations R334W, R347P, R1162X, and 3849 + 10kbC-->T provide evidence of mutation recurrence in the CFTR gene","volume":"55","author":"Morral","year":"1994","journal-title":"Am. J. Hum. Genet."},{"key":"B39","doi-asserted-by":"publisher","first-page":"2503","DOI":"10.1093\/nar\/17.7.2503","article-title":"Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS)","volume":"17","author":"Newton","year":"1989","journal-title":"Nucleic Acids Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.jcf.2013.07.001","article-title":"Clinical presentation of mild cystic fibrosis in a Serbian patient homozygous for the CFTR mutation c.1393-1G>A","volume":"13","author":"Nikolic","year":"2014","journal-title":"J. Cyst. Fibros."},{"key":"B41","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1353\/hub.2001.0022","article-title":"Cystic fibrosis mutations and associated haplotypes in Turkish cystic fibrosis patients","volume":"73","author":"Onay","year":"2001","journal-title":"Hum. Biol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"6234","DOI":"10.1038\/s41598-019-42404-6","article-title":"Novel, rare and common pathogenic variants in the CFTR gene screened by high-throughput sequencing technology and predicted by in silico tools","volume":"9","author":"Pereira","year":"2019","journal-title":"Sci. Rep."},{"key":"B43","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.jcf.2006.07.004","article-title":"CFTR gene analysis in Latin American CF patients: Heterogeneous origin and distribution of mutations across the continent","volume":"6","author":"P\u00e9rez","year":"2007","journal-title":"J. Cyst. Fibros."},{"key":"B44","doi-asserted-by":"publisher","first-page":"554","DOI":"10.3390\/genes11050554","article-title":"Analysis of CFTR mutation spectrum in ethnic Russian cystic fibrosis patients","volume":"11","author":"Petrova","year":"2020","journal-title":"Genes (Basel)"},{"key":"B45","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1089\/gte.2004.8.276","article-title":"Spectrum of cystic fibrosis mutations in Serbia and Montenegro and strategy for prenatal diagnosis","volume":"8","author":"Radivojevic","year":"2004","journal-title":"Genet. Test."},{"key":"B46","doi-asserted-by":"publisher","first-page":"e88","DOI":"10.1136\/jmg.40.7.e88","article-title":"Transcript analysis of the cystic fibrosis splicing mutation 1525-1G>A shows use of multiple alternative splicing sites and suggests a putative role of exonic splicing enhancers","volume":"40","author":"Ramalho","year":"2003","journal-title":"J. Med. Genet."},{"key":"B47","doi-asserted-by":"publisher","first-page":"15010","DOI":"10.1038\/nrdp.2015.10","article-title":"Cystic fibrosis","volume":"1","author":"Ratjen","year":"2015","journal-title":"Nat. Rev. Dis. Prim."},{"key":"B48","doi-asserted-by":"publisher","first-page":"635183","DOI":"10.1100\/2012\/635183","article-title":"Beta-thalassemia in Iran: New insight into the role of genetic admixture and migration","volume":"2012","author":"Rezaee","year":"2012","journal-title":"Sci. World J."},{"key":"B49","doi-asserted-by":"publisher","first-page":"e57","DOI":"10.1093\/nar\/gnf056","article-title":"Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification","volume":"30","author":"Schouten","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"B50","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.jmoldx.2015.07.005","article-title":"The spectrum of CFTR variants in nonwhite cystic fibrosis patients: Implications for molecular diagnostic testing","volume":"18","author":"Schrijver","year":"2016","journal-title":"J. Mol. Diagn"},{"key":"B51","doi-asserted-by":"publisher","first-page":"589","DOI":"10.3390\/genes11060589","article-title":"The changing epidemiology of cystic fibrosis: Incidence, survival and impact of the CFTR gene discovery","volume":"11","author":"Scotet","year":"2020","journal-title":"Genes (Basel)"},{"key":"B52","doi-asserted-by":"publisher","first-page":"e0133890","DOI":"10.1371\/journal.pone.0133890","article-title":"Distribution of cystic fibrosis transmembrane conductance regulator (CFTR) mutations in a cohort of patients residing in Palestine","volume":"10","author":"Siryani","year":"2015","journal-title":"PLoS One"},{"key":"B53","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1637\/11080-040715-RegR","article-title":"Assessment of the potential distance of dispersal of high pathogenicity avian influenza virus by wild mallards","volume":"60","author":"\u015amietanka","year":"2015","journal-title":"Avian Dis."},{"key":"B54","doi-asserted-by":"publisher","first-page":"6","DOI":"10.22034\/ibj.22.1.6","article-title":"Molecular basis of \u03b1-thalassemia in Iran","volume":"22","author":"Valaei","year":"2018","journal-title":"Iran. Biomed. J."},{"key":"B55","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1093\/tropej\/50.2.120","article-title":"Rare CFTR mutation 1525-1G>A in a Pakistani patient","volume":"50","author":"Wahab","year":"2004","journal-title":"J. Trop. Pediatr."},{"key":"B56","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1097\/00005176-199705000-00010","article-title":"The estimated incidence of cystic fibrosis in Japan","volume":"24","author":"Yamashiro","year":"1997","journal-title":"J. Pediatr. Gastroenterology Nutr."},{"key":"B57","doi-asserted-by":"publisher","first-page":"e89094","DOI":"10.1371\/journal.pone.0089094","article-title":"CFTR mutations spectrum and the efficiency of molecular diagnostics in Polish cystic fibrosis patients","volume":"9","author":"Zietkiewicz","year":"2014","journal-title":"PLoS One"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1140034\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T17:18:56Z","timestamp":1684430336000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1140034\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,18]]},"references-count":57,"alternative-id":["10.3389\/fgene.2023.1140034"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2023.1140034","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,18]]},"article-number":"1140034"}}