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GENATLAS PHENOTYPE
last update : 27-02-2013
Symbol FTDU17
Location 17q21.31
Name familial frontotemporal dementia, tau-negative
Other name(s) hereditary dysphasic disinhibition dementia
Corresponding gene GRN
Other symbol(s) HDDD, FTLD-U
Main clinical features
  • frontotemporal dementia with progressive cognitive deficits with memory loss and personality changes, severe dysphasic disturbances leading to mutism, and hyperphagia
  • progressive aphasia, and/or semantic language deficits (PMID: 21368173))
  • neuropathologic examination showed asymmetrical focal cerebral atrophy (characteristic of Pick disease), neuritic plaques (characteristic of Alzheimer disease), and depletion of neurons in the pigmented nuclei of the brainstem (characteristic of paralysis agitans)
  • intraneuronal deposition of aggregated tau, TARDBP, or FUS proteins
  • at cereebral MRI, temporoparietal atrophy (PMID: 22366795))
    • Genetic determination autosomal dominant
    Prevalence . 10 to 20p100 of patients with familial FTLD (PMID: 22028881) . 5-10 p100 of all cases of FTLD
    Related entries . FTDP17
    Function/system disorder neurology
    Type disease
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    unknown   haploinsufficiency  
    frameshift   truncated protein premature termination codons
    frameshift   truncated protein severely affect protein folding and/or processing leading to PGRN protein haploinsufficiency
    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 (FTDP17) and the other to mutations in the GRN gene with tau-negative, ubiquitin-positive deposits
  • disease-associated progranulin mutations result in nonsense-mediated decay of progranulin mRNA or an inability to secrete the mutant protein
  • 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))
    • Genotype/Phenotype correlations It is likely that reduced GRN expression is associated with the progression of other neurodegenerative brain diseases including Alzheimer disease