RESUMO
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Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Polineuropatias/complicações , Síndrome de Churg-Strauss/complicações , Citostáticos/uso terapêutico , Corticosteroides/uso terapêutico , Diagnóstico PrecoceRESUMO
Mutations in the ATP6 gene are reported to be associated with Leber hereditary optic neuropathy, bilateral striatal necrosis, coronary atherosclerosis risk and neuropathy, ataxia and retinitis pigmentosa (NARP)/maternally inherited Leigh syndromes. Here, we present a patient with NARP syndrome, in whom a previously undescribed mutation was detected in the ATP6 gene: m.8839G>C. Several observations support the concept that m.8839G>C is pathogenically involved in the clinical phenotype of this patient: (1) the mutation was heteroplasmic in muscle; (2) mutation load was higher in the symptomatic patient than in the asymptomatic carriers; (3) cybrids carrying this mutation presented lower cell proliferation, increased mitochondrial DNA (mtDNA) copy number, increased steady-state OxPhos protein levels and decreased mitochondrial membrane potential with respect to isogenic wild-type cybrids; (4) this change was not observed in 2959 human mtDNAs from different mitochondrial haplogroups; (5) the affected amino acid was conserved in all the ATP6 sequences analyzed; and (6) using in silico prediction, the mutation was classified as 'probably damaging'. However, measurement of ATP synthesis showed no differences between wild-type and mutated cybrids. Thus, we suggest that m.8839G>C may lower the efficiency between proton translocation within F0 and F1 rotation, required for ATP synthesis. Further experiments are needed to fully characterize the molecular mechanisms involved in m.8839G>C pathogenicity.
Assuntos
Miopatias Mitocondriais/genética , ATPases Mitocondriais Próton-Translocadoras/genética , Mutação de Sentido Incorreto , Retinose Pigmentar/genética , Trifosfato de Adenosina/biossíntese , Linhagem Celular Tumoral , Proliferação de Células , DNA Mitocondrial/genética , Feminino , Dosagem de Genes , Haplótipos , Heterozigoto , Humanos , Pessoa de Meia-Idade , Miopatias Mitocondriais/diagnóstico , Miopatias Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Fosforilação Oxidativa , Retinose Pigmentar/diagnóstico , Retinose Pigmentar/metabolismoRESUMO
We describe 2 cases of tuberous sclerosis in a 17 and a 27 years old patients in which images compatible with a cardiac rhabdomioma were detected during an echocardiographic study. In one of the cases these images were multiple. We point out the few clinical repercussions they caused and the length of their undetected presence. We revise the clinical features and diagnosis of these rare tumours and comment on the need to withhold surgical treatment in situations which could put the patient's life in danger.
