Assuntos
Mutação/genética , Doença da Deficiência de Ornitina Carbomoiltransferase/diagnóstico , Doença da Deficiência de Ornitina Carbomoiltransferase/genética , Adulto , Extubação , Substituição de Aminoácidos , Aminoácidos/sangue , Aminoácidos/urina , Amônia/sangue , Ciclismo/fisiologia , Diagnóstico Precoce , Humanos , Masculino , Mutação/fisiologia , Doença da Deficiência de Ornitina Carbomoiltransferase/dietoterapia , Agitação Psicomotora/etiologia , Rabdomiólise/etiologiaRESUMO
MCAD deficiency is the most common fatty acid oxidation disorder, with the prevalence varying from 1/10,000 to 1/27,000 in the countries adjacent to France. As the High Authority for Health has recently proposed including MCAD deficiency in the panel of diseases neonatally screened for in France, a consensus was written for the management of MCAD deficiency diagnosed either clinically or by neonatal screening. Patients may present acutely with hyperammonemia, hypoglycemia, encephalopathy, and hepatomegaly, mainly after a prolonged fast of intercurrent infection. Sudden death related to heartbeat disorders may also occur. The diagnosis of MCAD deficiency is suspected on the plasma acylcarnitine and/or the urinary organic acid profile. The diagnosis is confirmed by molecular biology and the enzymatic activity for patients who are not homozygous for the main mutation c.985A>G. However, some MCAD-deficient individuals may remain asymptomatic throughout life. The mainstay of treatment consists in avoiding prolonged fast and prescribing l-carnitine for patients who exhibit a deficiency in plasma carnitine. This management has radically modified the natural history of MCAD deficiency. This consensus will allow homogeneous management of these patients once the neonatal screening of MCAD deficiency has been introduced in France.
Assuntos
Erros Inatos do Metabolismo Lipídico/diagnóstico , Erros Inatos do Metabolismo Lipídico/terapia , Triagem Neonatal , Acil-CoA Desidrogenase/deficiência , Árvores de Decisões , França , Humanos , Recém-Nascido , Erros Inatos do Metabolismo Lipídico/fisiopatologiaRESUMO
Rett syndrome (RTT) is a severe progressive neurological disorder that affects almost exclusively females. The gene responsible for this disorder, MECP2, was recently identified by candidate gene strategy. Mutations were detected in 70-85% of RTT cases. We report here five novel frameshift mutations (named 345delC, 895del202, 989ins18del8, 996insAG and 1124del53) in exon 3 and 4 of the MECP2 gene. To avoid the missing of few small deletions in RTT patients using classical mutation screening approaches, we suggest that screening of the mutations in the MECP2 gene in RTT girls should include at least a large PCR to amplify exon 4 entirely.
Assuntos
Proteínas Cromossômicas não Histona , Proteínas de Ligação a DNA/genética , Éxons/genética , Proteínas Repressoras , Síndrome de Rett/genética , DNA/química , DNA/genética , Análise Mutacional de DNA , Mutação da Fase de Leitura , Humanos , Proteína 2 de Ligação a Metil-CpGRESUMO
Following the recent discovery that the methyl-CpG binding protein 2 (MECP2) gene located on Xq28 is involved in Rett syndrome (RTT), a wild spectrum of phenotypes, including mental handicap, has been shown to be associated with mutations in MECP2. These findings, with the compelling genetic evidence suggesting the presence in Xq28 of additional genes besides RabGDI1 and FMR2 involved in non-specific X-linked mental retardation (MRX), prompted us to investigate MECP2 in MRX families. Two novel mutations, not found in RTT, were identified. The first mutation, an E137G, was identified in the MRX16 family, and the second, R167W, was identified in a new mental retardation (MR) family shown to be linked to Xq28. In view of these data, we screened MECP2 in a cohort of 185 patients found negative for the expansions across the FRAXA CGG repeat and reported the identification of mutations in four sporadic cases of MR. One of the mutations, A140V, which we found in two patients, has been described previously, whereas the two others, P399L and R453Q, are novel mutations. In addition to the results demonstrating the involvement of MECP2 in MRX, this study shows that the frequency of mutations in MECP2 in the mentally retarded population screened for the fragile X syndrome is comparable to the frequency of the CGG expansions in FMR1. Therefore, implementation of systematic screening of MECP2 in MR patients should result in significant progress in the field of molecular diagnosis and genetic counseling of mental handicap.
Assuntos
Proteínas Cromossômicas não Histona , Ilhas de CpG/genética , Proteínas de Ligação a DNA/genética , Ligação Genética , Deficiência Intelectual/genética , Mutação , Proteínas de Ligação a RNA , Cromossomo X/genética , Adulto , Sequência de Bases , Feminino , Proteína do X Frágil da Deficiência Intelectual , Humanos , Masculino , Proteína 2 de Ligação a Metil-CpG , Pessoa de Meia-Idade , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/genética , Linhagem , Proteínas Repressoras/genética , Síndrome de Rett/genética , Fatores SexuaisRESUMO
The c-Fos and c-Jun oncoproteins and the p53 tumor suppressor protein are short-lived transcription factors. Several catabolic pathways contribute to their degradation in vivo. c-Fos and c-Jun are thus mostly degraded by the proteasome, but there is indirect evidence that, under certain experimental/physiological conditions, calpains participate in their destruction, at least to a limited extent. Lysosomes have also been reported to participate in the destruction of c-Fos. Along the same lines, p53 is mostly degraded following the ubiquitin/proteasome pathway and calpains also seem to participate in its degradation. Moreover, c-Fos, c-Jun and p53 turnovers are regulated upon activation of intracellular signalling cascades. All taken together, these observations underline the complexity of the mechanisms responsible for the selective destruction of proteins within cells.