Frontotemporal Dementia Linked to Chromosome 3

Abstract

A large pedigree with autosomal dominant frontotemporal dementia has been identified. Positional cloning has linked the disease gene to the pericentromeric region of chromosome 3. Clinical, neuropsychological, imaging, pathological and molecular genetic data are presented. The genetic mutation responsible for the disease has not been identified.

Prominent phenotypic variability associated with mutations in Progranulin

“…The MRI findings in FTD linked to charged multivesicular body protein 2B (CHMP2B) on chromosome 3 (Brown et al 2004;Skibinski et al 2005), to the valosin-containing protein (VCP) on chromosome 9 (Vance et al 2006) and to MAPT on chromosome 17 have been frontotemporal cortical abnormalities varying from symmetric to markedly asymmetric atrophy (Basun et al 1997;Rosso et al 2001;Boeve et al 2005). Most descriptions of MRI findings in sporadic and familial FTD have not reported subcortical white matter signal changes.…”

Cognitive impairment in the preclinical stage of dementia in FTD-3CHMP2Bmutation carriers: a longitudinal prospective study

“…However, the estimated average age of onset is 58 years of age and the mean duration 10 years, but with great variability 6. At the stage of clinical dementia, CT scans of FTD-3 patients typically show global cortical atrophy 7. However, a serial MRI study of nine presymptomatic mutation carriers showed increased atrophy rates in the inferior temporal cortex, superior frontal cortex and the insular cortex when compared to non-carriers,8 supporting the notion that the disease starts in the anterior brain regions before it spreads to other parts of the brain.…”

Frontotemporal dementia in Oman: Cognitive behavioural profile and neuroimaging characteristics; A prospective hospital-based study

“…Up to 45% of all FTD cases show a familial pattern of inheritance, with mutations in the tau gene on chromosome 17 associated with the disease [45]. However, studies have also shown linkage to chromosomes 3 [46][47][48] and 9 [49]. Although tau mutations do not account for the majority of familial cases, we suggested molecular genetic analysis for tauopathy/FTDP-17 to be done abroad, and brain biopsy for neuropathological confirmation of FTD.…”