Frequência das mutações F508del, G542X, 3120+1G>A e caracterização fenotípica em população miscigenada com Fibrose Cística na Bahia

Abstract

Frequency of the mutations F508del, G542X, 3120 + 1G> A and phenotypic characterization in a population mixed with Cystic Fibrosis in Bahia. Cystic fibrosis (CF) is an autosomal recessive genetic disorder due to mutations in the gene that encodes the Cystic Fibrosis Transmembrane Regulator (CFTR) protein. FC is little studied in the Brazilian Northeast, particularly in the State of Bahia that has a very mixed population. The identification of the genetic mutations can contribute to the diagnosis, besides proposing the genotype/phenotype correlation, being also important for the prognosis and treatment of the disease. Objectives: To determine the frequency of the F508del, G542X and 3120 + 1G> A mutations and to describe the clinical characteristics of patients with CF in a reference center in Salvador. Methods: A cross-sectional study was performed. The studied population was composed of patients with CF from 0 to 20 years of age followed up in a multidisciplinary service. It was filled out form for obtaining the clinical data, followed by blood collection for the investigation of the mutations. Results: Fifty-five patients were included, of which 29 (52.7%) were male. Fifty-four non-white patients (98.2%). The mean age at diagnosis was 5.2 years (SD = 5.2 years), with a median of 3.6 years (1 month - 15.8 years). The mean time between onset of symptoms and diagnosis was 3.9 years (SD = 4.3 years), with a median of 2.6 years (the minimum period of 2 months in which the diagnosis preceded the onset of symptoms, and the maximum of 14.0 years). Mutations were identified in 26 children (47.3%), eleven homozygotes (44%) for F508del and 15 (57.7%) were heterozygous for one of the three mutations. The allelic frequencies for the F508del, 3120 + 1G> A and G542X mutations were 31.8%, 5.4% and 3.6%, respectively. Among the patients with identified mutations, 22 (84.6%) had respiratory symptoms, 23 (88.5%) had difficulty gaining weight and 19 (73.1%) had steatorrhea at the time of diagnosis. Conclusions: The F508del mutation was the most frequent, however, it presented lower allele frequency than observed in Causes. The allelic frequency of the 3120 + 1G> A mutation was lower when compared to the African population, while the G542X mutation presented frequency similar to that described worldwide. The diagnosis of CF was late, but earlier among patients with mutations identified, also presenting a shorter time between onset of symptoms and diagnosis. The clinical manifestations in the patients with mutation correspond to those that make up the classic disease, as well as these had higher values in the sweat test, mainly the patients that presented mutations belonging to the Class I.