title: Mutational spectrum of cystic fibrosis patients from Córdoba province and its zone of influence: implications of molecular diagnosis in Argentina.
abstract: Cystic Fibrosis (CF) is an autosomal recessive disorder affecting 1/2000-4000 newborns in Caucasian populations. This lethal disease mainly affects respiratory and digestive organs as well as fertility in man. So far, the CF prevalence and mutational spectrum have showed specificity among populations and regions, making it necessary to establish them in each one. In this study, we present the spectrum and frequency of CFTR gene mutations in CF patients from Córdoba (a province with 3.1 millions inhabitants in the middle of Argentina) and its zone of influence, to offer an accurate genetic testing. The study includes 78 families in which 98 patients fulfilled clinical criteria to CF diagnosis. The strategy for the molecular diagnosis comprised analysis of 21 common mutations, microsatellite haplotypes and the complete CFTR gene analysis using scanning techniques followed by sequencing of the abnormal migration patterns. Our first step led us to the identification of 10 mutations that represented 76% of alleles. Another four mutations (p.R1066C, c.1811 + 1.6 kbA > G, c.711 + 1G > T, and p.G85E) were found based on the microsatellite haplotype-mutation association. Finally, 14 mutations were characterized after the CFTR gene scanning, three of them are not previously described (p.G27R, c.622-2A > G, and p.W277R). In summary, we have identified 27 mutations accounting for 94.23% of CF alleles. This characteristic mutational spectrum highlights the 14 most frequent mutations (>1%) in the Córdoba region.
authors.affiliation: Centro de Estudio de las Metabolopatías Congénitas, CEMECO, Cátedra de Clínica Pediátrica, Facultad de Ciencias Médicas, UNC, Hospital de Niños, Córdoba, Argentina. ramirezoller@agora.com.ar
authors.forename: Ana María Oller
authors.initials: AM
authors.lastname: Ramírez
authors.forename: María D
authors.initials: MD
authors.lastname: Ramos
authors.forename: Javier
authors.initials: J
authors.lastname: Jiménez
authors.forename: Addy
authors.initials: A
authors.lastname: Ghio
authors.forename: Myrna Melano
authors.initials: MM
authors.lastname: de Botelli
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Rezzónico
authors.forename: Inés
authors.initials: I
authors.lastname: Marqués
authors.forename: Silvia
authors.initials: S
authors.lastname: Pereyro
authors.forename: Teresa
authors.initials: T
authors.lastname: Casals
authors.forename: Raquel Dodelson
authors.initials: RD
authors.lastname: de Kremer
mesh_terms: D000328:Adult; D001118:Argentina; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator