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GENATLAS PHENOTYPE
last update : 27-02-2013
Symbol FTDP17
Location 17q21.31
Name frontotemporal dementia with parkinsonism
Other name(s) hereditary Pick disease :
  • pallido-ponto-nigral degeneration (OMIM 168610 )
  • dysphasic disinhibition, dystonia, muscular atrophy
  • amyotrophic lateral sclerosis- parkinsonism- dementia complex, lytico-bodig of Guam (OMIM 601104)
  • multiple system tauopathy with presenile dementia
    • Corresponding gene MAPT
    Other symbol(s) FPDEM, FTDP, HDDD, PPND, DDPAC, MSTD
    Main clinical features
  • with obsessive-compulsive behaviour and parkinsonism with variable phenotypes, progressive subcortical gliosis and pathological features
    • comprising neuronal loss, spongy change in multiple areas of neocortex, presence of prions or double PHF-tau, neurofibrillar tangles or ubiquitin-positive inclusions
  • at cerebral MRI, striking anteromedial temporal atrophy (PMID: 22366795))
    • Genetic determination autosomal dominant
    Related entries FTDU17, familial cortico-basal degeneration
    Function/system disorder neurology
    psychiatric disorder
    Type disease
    Gene product
    Name microtubule associated protein tau 1 (MAPT)
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    abnormal splicing   other mutations affecting multiple alternative splicing regulatory elements such as mutation N279K and Del280K.
    various types      
    Remark(s)
  • two genetically distinct types of fronto temporal dementia are linked to 17q21, one is due to mutation in the MAPT gene and is associated with tau deposition in the brain of patients and the other to mutations in th GRN gene with tau-negative, ubiquitin-positive deposits (FTDU17)
  • mutation causing misregulation of microtubule dynamics, plays a fundamental role in Tau-mediated neuronal cell death (PMID: 18940799))
  • missense mutations, by promoting phosphorylation at Ser202, inhibit the microtubule assembly-promoting activity of tau, suggesting that Ser202 phosphorylation plays a major role in the development of neurofibrillary tangles pathology in AD and related tauopathies (PMID: 19304664))
  • SAHA (suberoylanilide hydroxamic acid ) has demonstrated therapeutic potential in several neurodegenerative diseases and thus holds promise as a first generation drug for the prevention and treatment of frontotemporal dementia (PMID: 21454553))