{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T11:04:25Z","timestamp":1769857465407,"version":"3.49.0"},"reference-count":32,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T00:00:00Z","timestamp":1730937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN)","award":["#12\/2015\/I"],"award-info":[{"award-number":["#12\/2015\/I"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Cystic fibrosis (CF) is a rare autosomal recessive disease most commonly affecting the Caucasian population. CF diagnosis can be a challenge due to the large spectrum of pathogenic variants in the CFTR gene and the effects of complex alleles. Next-generation sequencing has improved our understanding of the contribution of these complex alleles to the wide spectrum of CF clinical symptoms and to the response to medications. Herein, we studied nine CF patients from six unrelated families carrying the complex allele p.[Ile148Thr;Ile1023_Val1024del] with a frequency of 0.18%. All patients were from Central Mexico. This complex allele was found in trans with Class I and II pathogenic variants such as p.(Phe508del), and p.(Phe1078Profs*77)]. A targeted search of a dataset of 2217 exomes from healthy individuals revealed that eight individuals (0.18%) carried the p.(Ile148Thr) variant, but only one (0.022%), who was also born in Central Mexico, was a carrier of the complex allele. These findings show an enrichment of this p.[Ile148Thr;Ile1023_Val1024del] complex allele in Mexican CF patients in this region of Mexico. Finally, protein modeling revealed that this complex allele disrupts the secondary structure of the CFTR protein and might alter the ion flow.<\/jats:p>","DOI":"10.3390\/life14111445","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T07:47:16Z","timestamp":1730965636000},"page":"1445","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effect of the Complex Allele p.[Ile148Thr;Ile1023_Val1024del] in Cystic Fibrosis and Tracing of a Founder Effect in Mexican Families"],"prefix":"10.3390","volume":"14","author":[{"given":"Namibia Guadalupe","family":"Mendiola-Vidal","sequence":"first","affiliation":[{"name":"Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Gen\u00f3mica, Secretar\u00eda de Salud, Tlalpan, Mexico City 14610, Mexico"},{"name":"Maestr\u00eda en Ciencias M\u00e9dicas, Posgrado de Maestr\u00eda y Doctorado en Ciencias M\u00e9dicas, Odontol\u00f3gicas y de la Salud, Sede: Hospital General Dr. Manuel Gea Gonz\u00e1lez, UNAM, Coyoac\u00e1n, Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7994-3831","authenticated-orcid":false,"given":"Cecilia","family":"Contreras-Cubas","sequence":"additional","affiliation":[{"name":"Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Gen\u00f3mica, Secretar\u00eda de Salud, Tlalpan, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5064-6203","authenticated-orcid":false,"given":"Francisco","family":"Barajas-Olmos","sequence":"additional","affiliation":[{"name":"Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Gen\u00f3mica, Secretar\u00eda de Salud, Tlalpan, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Rafael","family":"Villafan-Bernal","sequence":"additional","affiliation":[{"name":"Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Gen\u00f3mica, Secretar\u00eda de Salud, Tlalpan, Mexico City 14610, Mexico"},{"name":"Investigador por M\u00e9xico, Consejo Nacional de Humanidades, Ciencia y Tecnolog\u00eda (CONAHCYT), Benito Ju\u00e1rez, Mexico City 03940, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1662-9239","authenticated-orcid":false,"given":"Ana Lucia","family":"Ya\u00f1ez-Felix","sequence":"additional","affiliation":[{"name":"Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Gen\u00f3mica, Secretar\u00eda de Salud, Tlalpan, Mexico City 14610, Mexico"},{"name":"Posgrado de Alta Especialidad en Medicina Gen\u00f3mica, Sede: Instituto Nacional de Medicina Gen\u00f3mica, Facultad de Medicina UNAM, Coyoac\u00e1n, Mexico City 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0453-980X","authenticated-orcid":false,"given":"Humberto","family":"Garc\u00eda-Ortiz","sequence":"additional","affiliation":[{"name":"Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Gen\u00f3mica, Secretar\u00eda de Salud, Tlalpan, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3512-4519","authenticated-orcid":false,"given":"Federico","family":"Centeno-Cruz","sequence":"additional","affiliation":[{"name":"Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Gen\u00f3mica, Secretar\u00eda de Salud, Tlalpan, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6224-6829","authenticated-orcid":false,"given":"Elvia","family":"Mendoza-Caamal","sequence":"additional","affiliation":[{"name":"Clinical Area, Instituto Nacional de Medicina Gen\u00f3mica, Secretar\u00eda de Salud, Tlalpan, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1042-8505","authenticated-orcid":false,"given":"Carmen","family":"Alaez-Verson","sequence":"additional","affiliation":[{"name":"Genomic Diagnostic Laboratory, Instituto Nacional de Medicina Gen\u00f3mica, Secretar\u00eda de Salud, Tlalpan, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4859-1703","authenticated-orcid":false,"given":"Juan Luis","family":"Jim\u00e9nez-Ru\u00edz","sequence":"additional","affiliation":[{"name":"Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Gen\u00f3mica, Secretar\u00eda de Salud, Tlalpan, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tulia","family":"Monge-C\u00e1zares","sequence":"additional","affiliation":[{"name":"Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Gen\u00f3mica, Secretar\u00eda de Salud, Tlalpan, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"Lieberman","sequence":"additional","affiliation":[{"name":"Human Genetic Department, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Coyoac\u00e1n, Mexico City 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicente","family":"Baca","sequence":"additional","affiliation":[{"name":"Rheumatology Department, Hospital de Pediatr\u00eda, CMN Siglo XXI IMSS, Cuauht\u00e9moc, Mexico City 06720, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5064-4790","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Lezana","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Clinic and Pulmonary Physiology Laboratory, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Secretar\u00eda de Salud, Cuauhtemoc, Mexico City 06720, Mexico"},{"name":"Asociaci\u00f3n Mexicana de Fibrosis Qu\u00edstica, A.C. Benito Juarez, Mexico City 03700, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ang\u00e9lica","family":"Mart\u00ednez-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Gen\u00f3mica, Secretar\u00eda de Salud, Tlalpan, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorena","family":"Orozco","sequence":"additional","affiliation":[{"name":"Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Gen\u00f3mica, Secretar\u00eda de Salud, Tlalpan, Mexico City 14610, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,7]]},"reference":[{"key":"ref_1","unstructured":"WHO Human Genetics Programme (2004). 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