Assuntos
Doenças dos Gânglios da Base/genética , Doenças dos Gânglios da Base/patologia , Neurodegeneração Associada a Pantotenato-Quinase/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Adolescente , Adulto , Idade de Início , Doenças dos Gânglios da Base/epidemiologia , Química Encefálica , Brasil/epidemiologia , Criança , Pré-Escolar , Distúrbios Distônicos/diagnóstico , Distúrbios Distônicos/genética , Feminino , Transtornos Heredodegenerativos do Sistema Nervoso/epidemiologia , Transtornos Heredodegenerativos do Sistema Nervoso/genética , Humanos , Ferro/metabolismo , Imageamento por Ressonância Magnética , Masculino , Mutação , Adulto JovemRESUMO
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Assuntos
Humanos , Adolescente , Feminino , Biópsia , Músculo Esquelético , Doença de Lafora , Corpos de Inclusão , Diagnóstico DiferencialRESUMO
The most common autosomal recessive form of nemaline myopathy is due to mutations in the nebulin gene. Among eight patients studied, we identified one, a 14-year-old girl, with a specific pattern of diffuse rods in muscle fibers. Western blot analysis detected absence of the C-terminal domain of nebulin. Protein analysis may represent a good screening method to direct molecular studies in the case of very large and complex genes such as the large 1298 kb nebulin gene.
Assuntos
Proteínas Musculares/genética , Mutação/fisiologia , Miopatias da Nemalina/genética , Adolescente , Western Blotting , Criança , Pré-Escolar , Feminino , Imunofluorescência , Humanos , Masculino , Fibras Musculares Esqueléticas/patologia , Proteínas Musculares/metabolismo , Miopatias da Nemalina/patologiaRESUMO
Nemaline myopathy is a structural congenital myopathy which may show both autosomal dominant and autosomal recessive inheritance patterns. Mutations in three different genes have been identified as the cause of nemaline myopathy: the gene for slow alpha-tropomyosin 3 (TPM3) at 1q22-23, the nebulin gene (NEB) at 2q21.1-q22, and the actin gene (ACTA1) at 1q42. The typical autosomal recessive form appears to be the most common one and is caused by mutations in the nebulin gene. We have studied the pattern of nebulin labeling, in patients with the typical congenital form (ten patients), the severe congenital form (two patients) or the mild, childhood-onset form (one patient), using antibodies against three different domains of nebulin. A qualitative and quantitative nebulin analysis in muscle tissue showed the presence of nebulin in myofibers from all patients. Some differences relating to the rod structure were observed. The majority of the largest subsarcolemmal rods were not labeled with the N2 nebulin antibody (I-band epitope) and showed an indistinct pattern with the two antibodies directed to the Z-band portion of nebulin (epitopes M176-181 and serine-rich domain). Diffuse rods were not revealed using the three antibodies. A discordant pattern of nebulin N2 epitope labeling was found in two affected sisters with a mutation in the nebulin gene, suggesting that modifications in nebulin distribution inside the rods might occur with the progression of the disease. Western blot analysis showed no direct correlation with immunofluorescence data. In nine patients, the band had a molecular weight comparable to the normal control, while in one patient, it was detected with a higher molecular weight. Our results suggest that presence/absence of specific nebulin Z-band epitopes in rod structures is variable and could depend on the degree of rod organization.
