RESUMEN
Based on our previous finding of the p.A382T founder mutation in ALS patients with concomitant parkinsonism in the Sardinian population, we hypothesized that the same variant may underlie Parkinson's disease (PD) and/or other forms of degenerative parkinsonism on this Mediterranean island. We screened a cohort of 611 patients with PD (544 cases) and other forms of degenerative parkinsonism (67 cases) and 604 unrelated controls for the c.1144G > A (p.A382T) missense mutation of the TARDBP gene. The p.A382T mutation was identified in nine patients with parkinsonism. Of these, five (0.9 % of PD patients) presented a typical PD (two with familiar forms), while four patients (6.0 % of all other forms of parkinsonism) presented a peculiar clinical presentation quite different from classical atypical parkinsonism with an overlap of extrapyramidal-pyramidal-cognitive clinical signs. The mutation was found in eight Sardinian controls (1.3 %) consistent with a founder mutation in the island population. Our findings suggest that the clinical presentation of the p.A382T TARDBP gene mutation may include forms of parkinsonism in which the extrapyramidal signs are the crucial core of the disease at onset. These forms can present PSP or CBD-like clinical signs, with bulbar and/or extrabulbar pyramidal signs and cognitive impairment. No evidence of association has been found between TARDBP gene mutation and typical PD.
Asunto(s)
Esclerosis Amiotrófica Lateral/genética , Proteínas de Unión al ADN/genética , Predisposición Genética a la Enfermedad/genética , Mutación/genética , Enfermedad de Parkinson/genética , Anciano , Femenino , Pruebas Genéticas/métodos , Genotipo , Humanos , Italia , Masculino , Persona de Mediana Edad , FenotipoAsunto(s)
Postura/fisiología , Trastornos de la Sensación/complicaciones , Parálisis Supranuclear Progresiva/complicaciones , Anciano , Humanos , Radioisótopos de Yodo , Masculino , Trastornos de la Sensación/diagnóstico por imagen , Parálisis Supranuclear Progresiva/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , TropanosAsunto(s)
Demencia Frontotemporal/genética , Trastornos Parkinsonianos/genética , Fenotipo , Proteínas/genética , Trastornos Psicóticos/genética , Trastornos de la Visión/genética , Apraxias/complicaciones , Apraxias/diagnóstico , Apraxias/genética , Proteína C9orf72 , Expansión de las Repeticiones de ADN/genética , Demencia Frontotemporal/complicaciones , Demencia Frontotemporal/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Neuronas Motoras/patología , Trastornos Parkinsonianos/complicaciones , Trastornos Parkinsonianos/diagnóstico , Trastornos Psicóticos/complicaciones , Trastornos Psicóticos/diagnóstico , Trastornos de la Visión/complicaciones , Trastornos de la Visión/diagnósticoRESUMEN
We have recently published data showing that a founder mutation of the TARDBP gene (p.A382T) accounts for approximately one third of amyotrophic lateral sclerosis (ALS) cases on the Mediterranean island of Sardinia (Chiò et al., 2011). In that report, we identified a 53-year-old man carrying a homozygous A382T missense mutation of the TARDBP gene with a complex neurological syndrome including amyotrophic lateral sclerosis, parkinsonian features, motor and vocal tics, and frontotemporal dementia (FTD). Due to the uniqueness of this case, here we provide a detailed clinical description, as well as neurophysiological, neuropsychological, and neuroimaging data for that case and his extended family.