RESUMO
Two ethnic Chinese men with clinico-radiologic features of Fragile X-associated tremor-ataxia syndrome (FXTAS) were found on genetic testing to have neuronal intranuclear inclusion disease (NIID), highlighting that NIID should be considered in the differential diagnosis of FXTAS. NIID may also be much more common than FXTAS in certain Asian populations.
Assuntos
Ataxia/diagnóstico , Síndrome do Cromossomo X Frágil/diagnóstico , Doenças Neurodegenerativas/diagnóstico , Tremor/diagnóstico , Idoso , Ataxia/fisiopatologia , Diagnóstico Diferencial , Síndrome do Cromossomo X Frágil/fisiopatologia , Humanos , Corpos de Inclusão Intranuclear , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/fisiopatologia , Tremor/fisiopatologiaRESUMO
Noncoding repeat expansions cause various neuromuscular diseases, including myotonic dystrophies, fragile X tremor/ataxia syndrome, some spinocerebellar ataxias, amyotrophic lateral sclerosis and benign adult familial myoclonic epilepsies. Inspired by the striking similarities in the clinical and neuroimaging findings between neuronal intranuclear inclusion disease (NIID) and fragile X tremor/ataxia syndrome caused by noncoding CGG repeat expansions in FMR1, we directly searched for repeat expansion mutations and identified noncoding CGG repeat expansions in NBPF19 (NOTCH2NLC) as the causative mutations for NIID. Further prompted by the similarities in the clinical and neuroimaging findings with NIID, we identified similar noncoding CGG repeat expansions in two other diseases: oculopharyngeal myopathy with leukoencephalopathy and oculopharyngodistal myopathy, in LOC642361/NUTM2B-AS1 and LRP12, respectively. These findings expand our knowledge of the clinical spectra of diseases caused by expansions of the same repeat motif, and further highlight how directly searching for expanded repeats can help identify mutations underlying diseases.
Assuntos
Ataxia/genética , Encéfalo/patologia , Síndrome do Cromossomo X Frágil/genética , Marcadores Genéticos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Distrofias Musculares/genética , Doenças Neurodegenerativas/genética , Tremor/genética , Expansão das Repetições de Trinucleotídeos/genética , Adulto , Ataxia/patologia , Encéfalo/metabolismo , Estudos de Casos e Controles , Feminino , Proteína do X Frágil da Deficiência Intelectual/genética , Síndrome do Cromossomo X Frágil/patologia , Estudo de Associação Genômica Ampla , Humanos , Corpos de Inclusão Intranuclear/genética , Corpos de Inclusão Intranuclear/patologia , Desequilíbrio de Ligação , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Masculino , Pessoa de Meia-Idade , Distrofias Musculares/patologia , Mutação , Doenças Neurodegenerativas/patologia , Neuroimagem/métodos , Linhagem , Tremor/patologiaRESUMO
Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease with marked variety in its clinical manifestations. While characteristic neuroimaging and skin biopsy findings are important clues to the diagnosis, autopsy studies are still important for confirming the exact disease features. We herein report the case of a patient who received an antemortem diagnosis of familial NIID with dementia-dominant phenotype that was later confirmed by an autopsy. Our report is the first to document a case of autopsy-confirmed NIID involving both cognitive impairment and sensorimotor neuropathy.