RESUMEN
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.
Asunto(s)
Ataxia/diagnóstico , Síndrome del Cromosoma X Frágil/diagnóstico , Enfermedades Neurodegenerativas/diagnóstico , Temblor/diagnóstico , Anciano , Ataxia/fisiopatología , Diagnóstico Diferencial , Síndrome del Cromosoma X Frágil/fisiopatología , Humanos , Cuerpos de Inclusión Intranucleares , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedades Neurodegenerativas/fisiopatología , Temblor/fisiopatologíaRESUMEN
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.
Asunto(s)
Ataxia/genética , Encéfalo/patología , Síndrome del Cromosoma X Frágil/genética , Marcadores Genéticos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Distrofias Musculares/genética , Enfermedades Neurodegenerativas/genética , Temblor/genética , Expansión de Repetición de Trinucleótido/genética , Adulto , Ataxia/patología , Encéfalo/metabolismo , Estudios de Casos y Controles , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/patología , Estudio de Asociación del Genoma Completo , Humanos , Cuerpos de Inclusión Intranucleares/genética , Cuerpos de Inclusión Intranucleares/patología , Desequilibrio de Ligamiento , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Masculino , Persona de Mediana Edad , Distrofias Musculares/patología , Mutación , Enfermedades Neurodegenerativas/patología , Neuroimagen/métodos , Linaje , Temblor/patologíaRESUMEN
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.
