CFTR allelic heterogeneity in Mexican patients with cystic fibrosis: implications for molecular screening

Rev Invest Clin. 2010 Nov-Dec;62(6):546-52.

Abstract

Introduction: Cystic fibrosis, the most common autosomal recessive disorder, is caused by defects in the CF transmembrane conductance regulator gene (CFTR) that encodes a chloride channel. To date, over 1,800 mutations have been described related to the causative gene of CF, showing a variable frequency among populations. In a previous extensive analysis of the CFTR locus in 97 Mexican patients, 34 different mutations (75% of CF alleles) were found using several strategies for mutation screening; however, 63% had at least an uncharacterized allele. Despite the combined technologies used, there are still a great number of unknown mutations in the Mexican population.

Objective: Screening of the CFTR gene to provide additional evidence of the mutational wide spectrum responsible for CF in Mexican patients.

Material and methods: In this study, the number of unrelated CF patients was increased to 230, 133 new cases and the 97 previously reported to include 63% with at least an uncharacterized allele. Additional tools were used to improve the detection rate of CF mutations, such as a commercial kit for 36 mutations plus a single chain conformational polymorphism method and DNA sequencing.

Results: By using a combination of these strategies we characterized 77.7% of all the CF alleles, resulting in a total of 46 different mutations detected, including the identification of 12 additional mutations (p.R334W, p.A455E, c.3120+1G > A, c.3272-26A > G, c.711+1G > T, p.Q552X, p.W1282X, c.IVS8-5T, p.R1162X and p.R347P, p.D1152H and p.T1036N). Although these 12 mutations have been reported in other populations, they have not yet been reported in Mexican patients. This report shows that Mexico has one of the widest spectra of CFTR mutations worldwide. The knowledge of the ethnic and geographic distribution of CFTR mutations in this population will allow the development of more effective methods for diagnosis and treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Child, Preschool
  • Cystic Fibrosis / epidemiology
  • Cystic Fibrosis / ethnology
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • DNA Mutational Analysis
  • Female
  • Gene Frequency
  • Genetic Testing*
  • Humans
  • Indians, North American / genetics
  • Male
  • Mexico / epidemiology
  • Mutation
  • Mutation, Missense
  • Polymorphism, Single-Stranded Conformational
  • White People / genetics

Substances

  • CFTR protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator