Assuntos
Doença de Niemann-Pick Tipo C/diagnóstico , Criança , Diagnóstico Diferencial , Progressão da Doença , Evolução Fatal , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Atividade Motora/fisiologia , Doença de Niemann-Pick Tipo C/fisiopatologia , Tomografia Computadorizada por Raios XRESUMO
Gaucher disease (GD) is the most frequent lysosomal storage disease presenting in all populations. Mutations in the acid beta-D-glucosidase gene (GBA) cause development of GD, resulting in a decrease or full loss of activity of this enzyme. We report here the results of the molecular-genetic analysis in 68 Russian GD patients from 65 families with the three types of the disease. We have identified 126 mutation alleles from 136 investigate alleles. In addition to known mutations p.N370S, c.1263-1317del (del55), p.L444P, p.R463C, Rec NciI, we identified rare mutations p.R120W, p.R170C, p.W184R, p.G202R, Rec C, presenting in other populations and mutations p.P236T, p.L249Q, p.L288P, p.P319S, p.V352M, p.W381X, p.A384D which are had not been described before.
Assuntos
Doença de Gaucher/genética , Glucosilceramidase/genética , Alelos , Feminino , Glucosilceramidase/análise , Glucosilceramidase/metabolismo , Humanos , Masculino , Mutação , Linhagem , Federação RussaRESUMO
A biochemical study of three patients with clinical symptoms of Gaucher disease was carried out. Two of them had a significant deficiency of beta-glucocerebrosidase activity (a primary enzyme defect) in leukocytes and an enormous increasing of chitotriosidase activity in blood plasma that confirmed the diagnosis of Gaucher disease. Some differences in stability of mutant enzymes were found in these two cases. Mutation analysis revealed two point mutations--N370S and L444P in beta-glucocerebrosidase gene of both patients. Correlation between clinical picture, peculiarities of enzymatic defect and genetic status of patients is discussed. The influence of some epigenetic factors on phenotypic manifestation of the disease is supposed.
Assuntos
Doença de Gaucher/diagnóstico , Glucosilceramidase/genética , Pré-Escolar , Ensaios Enzimáticos Clínicos , Doença de Gaucher/genética , Variação Genética , Humanos , FenótipoRESUMO
A programme for diagnosis and prevention of lysosomal, peroxisomal, and mitochondrial [respiratory chain diseases (RCD)] diseases was developed on clinical, biochemical, and molecular approaches. The authors made postnatal diagnosis was made in 674 patients from 516 families and prenatal diagnosis in 124 fetuses in 94 families at risk. DNA analysis of mutant alleles in the mucopolysaccharidoses (MPS) I, II, and VI revealed 14, 13, and 4 new mutant alleles in IDS, ASB, IDUA genes, respectively. The pressure of a mutation process played a major role in the distribution of mutant alleles leading to MPS I and VI, but along with this factor genetic drift and migration undoubtedly influenced the observed spectrum of IDUA alleles in Russia. A clinical phenotype of patients with different MPS was analyzed on the basis of uniform registration of 167 symptoms and signs in 249 patients. Special statistical approaches were developed to characterize early manifestations of different MPS and "unique" signs and symptoms for many of them and "phenotypic distances" between them. The similar problems were solved for RCD through uniform registration of 110 symptoms and signs in 54 patients with different syndromes: pathognomonic symptoms for the whole RCD and "unique" symptoms for syndromes were defined.
