IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Probable novel presenilin 1 mutation (p.Arg41Ser) as cause of early-onset Parkinsonism
Autor/es:
EMILIA GATTO; PERSI, G; ETCHEVERRY, J.L. ; ROJAS, G; ADRIÁN TURJANSKI,; DAPRAT, G.; ALLEGRI, R.; SERGIO I. NEMIROVSKY; GERÓNIMO DIBRA; PARISI, V.; MARTIN CESARINI; GERMÁN BIAGIOLI; MARCELO MARTI
Lugar:
Lisboa
Reunión:
Congreso; 4th Congress of the European Academy of Neurology; 2018
Institución organizadora:
European Academy of Neurology
Resumen:
Background and aims: Although Alzheimer?s disease (AD) and Parkinson?s disease (PD) are multifactorial neurodegenerative disorders having distinct genetic risk factors, studies have revealed a possible genetic links between them. Mutations in presenilin-1(PSEN1) accounts for the majority of cases of early-onset autosomal dominant AD as well as sporadic forms. Atypical presentations have been reported including extrapyramidal signs (parkinsonism, myoclonus, dystonia). In the last years, mutations involving the PSEN1 and PD genes such as PARK2, PINK1 and LRRK2 have been demonstrated. Objective: Report a case of PSEN1 mutation presenting with early-onset Parkinsonism (EOPD) phenotype.Methods: A 46-year?old Argentinian woman with a remarkable medical history of chronic iron deficiency anemia,and a positive family history of psychiatric disorders started at age 35 with progressive asymmetric left resting tremor, bradykinesia and rigidity. Wilson?s and Niemann-Pick type C disease resulted negative. EOPD was diagnosed. L-dopa/carbidopa (LD/C) and rotigotine were slowly titrated, with clinical improvement. Two years later, she reported mild difficulties with memory and attention during the last two years.Results: Neuropsychological examination showed a predominant frontal subcortical cognitive decline. Brain MRI showed moderate signs frontal atrophy and 18FDG-PET reduced metabolism in frontal cortex. PiB-PET (Pittsburgh compound) image was amyloid negative. Because of EOPD and family history a Next Generation Sequencing-NGS was performed on DNA extracted from whole blood. NGS analysis revealed a novel missense PSEN1 mutation position 14:73637540, A>T, p.Arg41Ser. Parental DNA analysis could not be examined.Conclusion: This missense PSEN1 was considered a potential causative mutation, given the phenotype and the occurrence of the mutation in a very conservative region