title: CFTR allelic heterogeneity in Mexican patients with cystic fibrosis: implications for molecular screening.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Subdirección de Medicina Experimental, Instituto Nacional de Pediatría, Coyoacán, México, DF. mchavez_s2003@yahoo.com.mx
authors.forename: Margarita
authors.initials: M
authors.lastname: Chávez-Saldaña
authors.forename: Emiy
authors.initials: E
authors.lastname: Yokoyama
authors.forename: José Luis
authors.initials: JL
authors.lastname: Lezana
authors.forename: Alessandra
authors.initials: A
authors.lastname: Carnevale
authors.forename: Miguel
authors.initials: M
authors.lastname: Macías
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Vigueras
authors.forename: Marisol
authors.initials: M
authors.lastname: López
authors.forename: Lorena
authors.initials: L
authors.lastname: Orozco
mesh_terms: D000483:Alleles; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D008297:Male; D008800:Mexico / Q000453:epidemiology; D009154:Mutation; D020125:Mutation, Missense; D018807:Polymorphism, Single-Stranded Conformational; D044465:White People / Q000235:genetics
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator