Abstract

OLLER DE RAMIREZ, Ana M; GHIO, Addy; MELANO DE BOTELLI, Myrna  and  DODELSON DE KREMER, Raquel. Molecular diagnosis of cystic fibrosis in 93 argentinean patients and detection of heterozygotes in affected families: Impact on health services and therapeutic advances. Arch. argent. pediatr. [online]. 2008, vol.106, n.4, pp.310-319. ISSN 0325-0075.

Introduction. The cystic fibrosis is an autosomal recessive disease caused by more than 1500 mutations and variants in the cystic fibrosis transmembrane conductance regulator gene. Objectives. To establish the spectrum and frequency of mutations on this gene in Argentinean patients.To detect heterozygotes in affected families. Patients and methods. We investigated 91 clinical and biochemically confirmed patients with 2 elevated sweat tests and 2 sterile adults. We worked with 165 relatives. The molecular diagnosis was accomplished in 3 serial stages: a) determination of 29 frequent mutations; b) haplotypes for microsatellites; c) an extensive screening of gene through single strand conformation analysis and multiplex denaturing gradient gel electrophoresis with sequencing of abnormal patterns. Once patient's genotype was confirmed, we investigated the heterozygotes' state in the relatives. Results. 1^st Objective: Fourteen mutations were identified. Three more mutations were detected and other 11 mutations were characterized, 3 of them novel (p.G27R, c.622-2A>G, p.W277R). In total, we have identified 28 mutations responsible for 90.3% of the mutated alleles, 14 with a higher frequency than 1%. 2^ndObjective: From 165 investigated people, 143 were confirmed as heterozygotes and with normal genotype 22. Conclusions. This work contributed to the molecular characterization of patients with classic and atypical phenotypes and to the detection of great numbers of carriers. New pharmacological therapeutic investigations are based on the mutation type. Therefore, knowledge of patients, mutations (genotype) has significant importance for the future application of specific therapies.

Keywords : Cystic fibrosis; Recessive autosomal; CFTR gene; Molecular diagnosis; Pharmacogenetic.

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