Skip to main content

Table 2 The profile of main genes mutation and its possible disease mechanisms in FTLD

From: Clinic, neuropathology and molecular genetics of frontotemporal dementia: a mini-review

Gene symbol MAPT C9ORF72 PGRN VCP CHMP2B
Full name Microtubule -associated protein tau Chromosome 9 open reading frame 72 Progranulin Valosin containing protein Chromatin modifying protein 2B
Chromosomal localization 17q21.32 9p21.2 17q21.32 9p13.3 3p11.2
. MAPT gives rise to six isoforms: three isoforms containing three amino-acid repeats (3R), and three isoforms with four repeats (4R) [79]. expressed as three major transcripts, the expanded G4C2 repeat is located in the proximal regulatory region of C9ORF72[70, 73]. encodes progranulin, a ubiquitously expressed growth factor precursor consisting of 7.5 granulin peptides. Encodes a ubiquitously expressed member of a family of ATPases associated with a wide range of cellular functions [85]. Encodes a component of the heteromeric ESCRT-III complex with functions in the endosomal-lysosomal and the autophagic protein degradation pathway.
Functions and possible role in the disease mechanism Mutations result in a change in ratio of 3R to 4R tau isoforms. Mutations affect the normal function of the tau protein to stabilise microtubules, increase the tendency of tau to form neurotoxic aggregates and disturb neuronal plasticity and axonal transport [80]. Repeat expansion results in near complete loss of the major gene transcripts. And accumulation of transcripts harboring the expanded G4C2 repeat in nuclear RNA foci [70]. a wide range of biological processes such as inflammation and wound repair, or in pathological conditions including tumorigenesis [82]. mutations reside at the interface between the D1 ATPase and the N-domain of the CDC48-like protein [85]. Expressed in neurons of all major brain regions. It is critical for development, sexual differentiation [88] and neuronal survival [89].
G4C2 repeat leads to neuronal cytoplasmic inclusions throughout theentire cortical thickness [81]. Neurotrophic function involved in neuronal survival and neurite outgrowth [83, 84]. mutations disturb ubiquitin-proteasome mediated protein degradation, autophagy, or both [86, 87]. Mutations affect the C-terminal end of the protein due to aberrant splicing [78].
   unidentified mechanisms exist.    
Estimated mutation frequency [[69, 72, 79, 81, 90] 0-50% 14-48% 3–26% <1% <1%