Effect of the Complex Allele p.[Ile148Thr;Ile1023_Val1024del] in Cystic Fibrosis and Tracing of a Founder Effect in Mexican Families

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 <i>in trans</i> 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.

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Publication Details

Journal
Life
Published
2024-11-07
DOI
https://doi.org/10.3390/life14111445
Citations
3
Primary Topic
Cystic Fibrosis Research Advances
Type
article
Field-Weighted Citation Impact
1.26

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article

Effect of the Complex Allele p.[Ile148Thr;Ile1023_Val1024del] in Cystic Fibrosis and Tracing of a Founder Effect in Mexican Families

Tulia Monge-Cázares, Humberto Garcia‐Ortíz, Ana Lucia Yanez‐Felix, Federico Centeno-Cruz et al.
3 citations
Life
Cystic Fibrosis Research Advances
1.26
article

Effect of the Complex Allele p.[Ile148Thr;Ile1023_Val1024del] in Cystic Fibrosis and Tracing of a Founder Effect in Mexican Families

Tulia Monge-Cázares, Humberto Garcia‐Ortíz, Ana Lucia Yanez‐Felix, Federico Centeno-Cruz, Vicente Baca, Esther Lieberman, Angélica Martínez‐Hernández, Elvia Mendoza‐Caamal, Juan Luis Jiménez-Ruíz, José Rafael Villafán-Bernal, Carmen Aláez‐Verson, Francisco Martin Barajas-Olmos, José Luis Lezana, Lorena Orozco, Cecilia Contreras-Cubas, Namibia Guadalupe Mendiola-Vidal
article en
3 citations

Abstract

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 <i>in trans</i> 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.

LifeVol. 14(11)
Mexican Social Security Institute (MX), Secretaria de Salud (MX), Hospital Infantil de México Federico Gómez (MX), National Institute of Genomic Medicine (MX), Hospital General Dr. Manuel Gea Gonzalez (MX), Asociación Mexicana de Psicología y Desarrollo Comunitario (MX), Instituto Nacional de Pediatria (MX), Secretaría de Ciencia, Humanidades, Tecnología e Innovación (MX)
Instituto Nacional de Medicina Genómica
Good health and well-being
Openalex Percentile: Top 18%
Cystic Fibrosis Research Advances
1.26
DOIOpen Access PDFOpenAlex
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