ABSTRACT
Around 10-15% of patients diagnosed with frontotemporal dementia (FTD) have a positive family history for FTD with an autosomal dominant pattern of inheritance. Since the identification of mutations in MAPT(microtubuleassociated protein tau gene) in 1998, over 10 other genes have been associated with FTD spectrum disorders, discussed in this review. Along with MAPT, mutations in GRN(progranulin) and C9orf72(chromosome 9 open reading frame 72) are the most commonly identified in FTD cohorts. The association of FTD and motor neuron disease (MND) can be caused by mutations in C9orf72and other genes, such as TARDBP(TAR DNA-binding protein), FUS(fused in sarcoma), UBQLN2(ubiquilin 2). Multisystem proteinopathy is a complex phenotype that includes FTD, Paget disease of the bone, inclusion body myopathy and MND, and can be due to mutations in VCP(valosing containing protein) and other recently identified genes.
Key words:
frontotemporal lobar degeneration; frontotemporal dementia; genetics; amyotrophic lateral sclerosis
MND: motor neuron disease; FTD: frontotemporal dementia; PDB: Paget disease of the bone; IBM: inclusion body myositis. Each color refers to a FTLD subtype. Please see text for more information regarding neuropathology. Even though TDP-43 pathology is present in UBQLN2 mutations, inclusions immunostained by antibodies against ubiquilin 2 have also been reported, and ubiquilin 2 might be the major abnormal protein in this mutation. Mutations in HNRNPA1 and HNRNPA2B1 are still lacking neuropathological studies confirming TDP-43 pathology in the central nervous system.