RESUMO
Duchenne muscular dystrophy (DMD) is a progressive hereditary muscular disease with X-linked recessive inheritance, that leads patients to premature death. The loss of dystrophin determines membrane instability, causing cell damage and inflammatory response. Macrophage migration inhibitory factor (MIF) is a cytokine that exerts pleiotropic properties and is implicated in the pathogenesis of a variety of diseases. Recently, converging data from independent studies have pointed to a possible role of MIF in dystrophic muscle disorders, including DMD. In the present study, we have investigated the modulation of MIF and MIF-related genes in degenerative muscle disorders, by making use of publicly available whole-genome expression datasets. We show here a significant enrichment of MIF and related genes in muscle samples from DMD patients, as well as from patients suffering from Becker's disease and limb-girdle muscular dystrophy type 2B. On the other hand, transcriptomic analysis of in vitro differentiated myotubes from healthy controls and DMD patients revealed no significant alteration in the expression levels of MIF-related genes. Finally, by analyzing DMD samples as a time series, we show that the modulation of the genes belonging to the MIF network is an early event in the DMD muscle and does not change with the increasing age of the patients, Overall, our analysis suggests that MIF may play a role in vivo during muscle degeneration, likely promoting inflammation and local microenvironment reaction.
Assuntos
Redes Reguladoras de Genes/imunologia , Oxirredutases Intramoleculares/metabolismo , Fatores Inibidores da Migração de Macrófagos/metabolismo , Distrofia Muscular de Duchenne/imunologia , Transdução de Sinais/genética , Estudos de Casos e Controles , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Voluntários Saudáveis , Humanos , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/imunologia , Fatores Inibidores da Migração de Macrófagos/genética , Fatores Inibidores da Migração de Macrófagos/imunologia , Fibras Musculares Esqueléticas/imunologia , Fibras Musculares Esqueléticas/patologia , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/imunologia , Distrofia Muscular do Cíngulo dos Membros/patologia , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/patologia , Miotonia Congênita/genética , Miotonia Congênita/imunologia , Miotonia Congênita/patologia , Transdução de Sinais/imunologiaRESUMO
The association between hereditary myotonic disorders and epilepsy is seldom described in the literature. To date, few reports have dealt with dystrophic myotonias, whereas a single case demonstrating an association between sporadic congenital myotonia and epilepsy was recently reported in a patient carrying a de novo mutation of the CLCN1 gene. Additional evidence for a role of CLCN1 in the pathogenesis of epilepsy is derived from large-scale exome analysis of ion channel variants and expression studies. Here, we describe the first case of association between familial Thomsen myotonia and epilepsy. All the affected members of a two-generation family presented myotonia and disclosed a pathogenic mutation in CLCN1. In addition, one individual experienced epileptic seizures due to limbic encephalitis (LE) with anti-GAD antibodies. The occurrence of the two diseases in this patient could be a chance association, however, CLCN1 mutation, as a susceptibility factor for epilepsy through dysfunction of GABAA inhibitory signalling, cannot be ruled out as a possible influence.
Assuntos
Glutamato Descarboxilase/imunologia , Encefalite Límbica/imunologia , Miotonia Congênita/imunologia , Adolescente , Canais de Cloreto/genética , Glutamato Descarboxilase/genética , Humanos , Encefalite Límbica/complicações , Encefalite Límbica/genética , Masculino , Mutação , Miotonia Congênita/complicações , Miotonia Congênita/genética , LinhagemRESUMO
Complete absence of C1q was demonstrated in the sera of 3 siblings in association with renal and cutaneous lesions. The serologic findings were consistent with an autoimmune disorder. Hematuria was the renal symptom present in all 3 patients; proteinuria was also present in 1. Renal biopsies showed mesangial proliferative glomerulonephritis with diffuse glomerular deposits of IgM and C3 in all cases. Clinical cutaneous manifestations and the histological picture were those of the Rothmund-Thompson syndrome. Three combined diseases, characterized by renal and cutaneous affection and serologic abnormalities, are presented in this paper.
