title: CFTR mutations in patients from Colombia: implications for local and regional molecular diagnosis programs.
abstract: Cystic Fibrosis is a worldwide distributed hereditary disease. The incidence of the main (p.F508del) and other frequent mutations has been determined in a great number of countries and ethnic groups, but its incidence in most Latin American countries has remained unknown until recently. It is now beginning to be recognized as a frequent cause of infant mortality, and some countries report the incidence of their mutations. Colombia started several years ago a concerted program of molecular study of patients which were clinically diagnosed as probable cystic fibrosis. We screened the whole CFTR (ABCC7) coding sequence in 92 patients from 6 different geographic regions, using conventional PAGE analyses and DGGE followed by sequencing. Additionally, we established the frequency of the p.F508del mutation in 130 unrelated healthy controls. The results of this pilot study in Colombian patients from various ethnic admixture show six main mutations: p.F508del (41.8%), c.1811+1.6kbA>G (6.5%), p.G542X (3.8%), p.S549R (2.2%), p.W1282X (1.1%) and p.R1162X (1.1%). Thirteen other rare mutations, including three novel, were detected, accounting for a total of 63.6% known mutations. There is a great variability between the geographic regions, both in the frequency of the p.F508del mutation and non-p.F508del CF chromosomes. Our results point to a varied origin of the disease genes. These results also show that careful scrutiny of the mutations is needed in each part of Latin America in order to establish priority-screening protocols adapted to each country and region.
authors.affiliation: Instituto de Genética, Universidad Nacional de Colombia, Bogotá, Colombia. gkeyeuxb@bacata.usc.unal.edu.co
authors.forename: Genoveva
authors.initials: G
authors.lastname: Keyeux
authors.forename: Clemencia
authors.initials: C
authors.lastname: Rodas
authors.forename: Thierry
authors.initials: T
authors.lastname: Bienvenu
authors.forename: Pilar
authors.initials: P
authors.lastname: Garavito
authors.forename: Dominique
authors.initials: D
authors.lastname: Vidaud
authors.forename: Dora
authors.initials: D
authors.lastname: Sanchez
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Kaplan
authors.forename: Gustavo
authors.initials: G
authors.lastname: Aristizábal
mesh_terms: D000328:Adult; D003105:Colombia / Q000453:epidemiology; D003550:Cystic Fibrosis / Q000453:epidemiology / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D006580:Genetic Carrier Screening; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D015994:Incidence; D008297:Male; D025202:Molecular Diagnostic Techniques / Q000379:methods / Q000639:trends*; D009154:Mutation; D010865:Pilot Projects
chemical_list: C505032:CFTR protein, human; C093349:cystic fibrosis transmembrane conductance regulator delta F508; D019005:Cystic Fibrosis Transmembrane Conductance Regulator