RESUMO
BACKGROUND: The Cystic Fibrosis (CF) carrier rate in Chile was estimated to be 1/40. CF is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Delta F508 mutation is the most common in CF patients in Chile and worldwide. Delta F508 has linkage disequilibrium with two Single Nucleotide Polymorphisms (SNP), often used to define the haplotypic frameworks of CF mutations. AIM: To know the frequency of the delta F508 mutation and to establish the SNPs, M470V and T854T, haplotypic frequency, in a Valparaiso general population sample. SUBJECTS AND METHODS: Fifty subjects were studied. Genetic material was obtained from blood samples, amplified by PCR and analyzed by restriction fragment length polymorphism. RESULTS: Two of the 100 chromosomes analyzed, carried the delta F508 mutation. Therefore, the observed frequency carrier rate (0.02) was higher than the expected (0.01). Both carrier chromosomes had the same SNPs haplotypic framework (1-2). In normal chromosomes, the haplotype 2-1 was the most common. DISCUSSION: These results suggest that the chromosomes that bear delta F508 mutation have most likely a Mediterranean European origin, since this haplotypic framework has been reported in that region. We suggest that CF could be more common in Valparaiso than it was previously.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Testes Genéticos , Haplótipos , Mutação , Polimorfismo de Nucleotídeo Único , Sequência de Bases , Chile , Fibrose Cística/diagnóstico , Etnicidade , Éxons , Feminino , Frequência do Gene , Marcadores Genéticos , Heterozigoto , Humanos , Masculino , Dados de Sequência Molecular , Reação em Cadeia da PolimeraseRESUMO
Isolated growth hormone deficiency (IGHD) is a disorder that leads to short stature. It has been classified into types IA, IB, II and III. GH gene mutations and growth hormone releasing hormone (GHRH) receptor gene mutations have been described in patients with IGHD. We report here a clinical and molecular study of 27 Chilean patients with IGHD. We performed GH stimulation tests with GHRH and GHRP, and segregation and molecular analysis of the GH, GHRH and GHRH receptor genes. We describe four patients with IGHD IA bearing a 7 kb mutation (13%), and two IGHD II patients who showed two different splice site point mutations (6.8%). In 21 patients, we did not find a mutation in any of the three genes examined. These results led us to conclude that the molecular causes of IGHD involve other genes besides those analyzed in this report, as has been reported previously in patients of different ethnic origins.
Assuntos
Hormônio do Crescimento Humano/classificação , Hormônio do Crescimento Humano/deficiência , Adolescente , Alelos , Estatura/efeitos dos fármacos , Estatura/genética , Criança , Pré-Escolar , Chile , Esquema de Medicação , Feminino , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/genética , Hormônio Liberador de Hormônio do Crescimento/administração & dosagem , Hormônio Liberador de Hormônio do Crescimento/farmacocinética , Humanos , Lactente , Injeções Intravenosas , Masculino , Mutação/genética , Oligopeptídeos/administração & dosagem , Oligopeptídeos/farmacocinética , Fenótipo , Receptores da Somatotropina/genéticaRESUMO
BACKGROUND: Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasian population. More than 900 mutations have been detected in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene. The most common worldwide, is a deletion of phenylalanine 508 (delta F508). AIM: To analyze the presence of mutations delta F508, G542X, N1303K, G551D, R553X and S549N in patients from the 5th Region of Chile, with a clinical diagnosis of CF. PATIENTS AND METHODS: We studied 17 non-related patients, presenting frequent respiratory tract infections, malabsorption and positive sweat tests, or meconial ileum. Serum immunoglobulins (IgG, IgA, IgM), and total, CD3+ and B-lymphocytes, were determined to discard the presence of an immune deficiency. The molecular study of the gene was performed by Polymerase Chain Reaction amplification and restriction analysis. RESULTS: Immunological parameters were normal in all patients. The delta F508 mutation was detected in 11 chromosomes and the mutation G542X in 3 chromosomes. CONCLUSIONS: The mutation G542X was the second most frequent mutation found in this sample of Chilean CF patients. Since this mutation has a high frequency in Spanish CF patients, we suggest that this mutation might have had its origin in Spain.