RESUMO
The main goal of this study was to determine and characterise the types of mutations in two monogenic human disorders: cystic fibrosis (CF) and Duchenne/Becker muscular dystrophy (DMD, BMD) and the susceptibility allele frequency in a polygenic disease: type I insulin-dependent diabetes mellitus (IDDM). After analysing 220 chromosomes for mutations in the CF (Cystic Fibrosis Transmembrane Conductance Regulator = CFTR) gene, delta F508 mutation was most abundant (41%) and out of the non-delta F508 CF mutations 5% was identified as G542X, G551D, R553X, N1303K and W1282X. The CF haplotype analysis by using linked markers to the CFTR gene revealed that the CF "B" haplotype occurred in 66.7% of patients, and this haplotype was 57.2% in patients carrying the delta F508 mutation. Prenatal genetic diagnosis for CF was performed in 10 fetuses: 3 were affected, 6 were carriers, and 1 without any CF mutation. Fifty % of 66 patients with DMB/BMD muscular dystrophy had one or more exon deletions in the dystrophin gene. Eighty-five % of the deletions occurred at the 3' and 15% at the 5' end of the gene. Out of the three prenatal diagnosis in one case DMD was substantiated. Thirty-six % of 50 patients with IDDM possessed four, 44% three and 20% two susceptibility markers in the HLA-DQA1, -DQB1 region. The onset of the disease correlated with the number of susceptibility alleles.
Assuntos
Doenças Genéticas Inatas/genética , Alelos , Criança , Fibrose Cística/diagnóstico , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Diabetes Mellitus Tipo 1/genética , Distrofina/genética , Feminino , Frequência do Gene , Marcadores Genéticos , Antígenos HLA-DQ/genética , Cadeias alfa de HLA-DQ , Cadeias beta de HLA-DQ , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Humanos , Masculino , Biologia Molecular , Distrofias Musculares/diagnóstico , Distrofias Musculares/genética , Mutação , Gravidez , Diagnóstico Pré-NatalRESUMO
The sodium and potassium concentrations of the red blood cells and the serum were investigated in 21 children with diabetes mellitus. Measurements were made prior to and 1 and 2 hours following insulin administration. Before insulin treatment, the sodium level in the red blood cells of the diabetes patients was significantly higher that the control level, while the potassium level was significantly depressed. These differences were not observed 1 and 2 hours following insulin administration. Attention is drawn to the rapid and extensive electrolyte changes in the red blood cells of diabetics in response to insulin. The potassium content of the serum of the diabetics was significantly decreased by insulin administration. No correlation was found between the electrolyte levels and the fasting blood glucose levels. A weak negative correlation (p less than 0.02) was observed between the potassium content of the red blood cells and the duration of the illness. The pathogenetic, diagnostic and therapeutic implications of the results are discussed.
