Table 1

Demographic and clinical characteristics of patients with ALS/FTD carrying probable or possible pathogenic mutations

CaseGenecDNA positionAmino acid changeGnomAD
SP_MAFGenderFHFTD variantFTD AAOALS SOOALS AAOAdditional data/neuropathological findings
1 TBK1 c.228+1G>Ap.K30_E76del00MbvFTD64Limb64
2 TBK1 c.235_237delp.T79del1.49×10–5 0MbvFTD55Limb56FTLD-MND-TDP type B, AGD III
3 TBK1 c.1921_1923delp.E643del2.4×10–5 0FbvFTD56Limb56
4 TBK1 c.992+4_7delp.G272_T331del00FbvFTD69Limb69
5* TBK1 c.762_763del†p.N254Kfs*400MnfvPPA53Limb49
5* SQSTM1 c.1175C>Tp.P392L0.0010.005
6 SQSTM1 c.1175C>Tp.P392L0.0010.005MbvFTD67NA68FTLD-MND-TDP type B, hippocampal sclerosis, basal ganglia degeneration, parkinsonism, PDB
7 SQSTM1 c.98C>Tp.A33V0.0010MbvFTD60Limb71FTLD-MND-TDP type B, hippocampal sclerosis, basal ganglia degeneration, scarce FUS, TAF15 and TNPO1
8 TAF15 c.1168T>A†p.S390T00MbvFTD49Limb45LMN>>UMN, dyskinesia
9 TAF15 c.1384G>A†p.G462S9.02×10–5 0M+bvFTD66Limb67FTLD-MND-TDP type B, parkinsonism, LMN>>UMN, mild AD changes
10 TARDBP c.269C>Tp.A90V0.00050M+bvFTD49Bulbar63MND-TDP stage 4, amygdalar gliosis
11 VCP c.79A>Gp.I27V9.47×10–5 0.001MbvFTD80Limb81MND-TDP, mild AD changes,  argyrophilic grains, bradykinesia, resting tremor
12 FIG4 c.590G>A†, ‡p.R197H00MbvFTD60Both61MND-TDP+hippocampal sclerosis
13 ERBB4 c.1997T>C†, ‡p.I666T1.79×10–5 0MbvFTD38Bulbar36
  • *Double mutation carrier.

  • †Novel mutations.

  • ‡Possible pathogenic category.

  • AAO: age at onset; AD, Alzheimer’s disease; AGD: argyrophilic grain disease; ALS, amyotrophic lateral sclerosis; bvFTD, behavioural variant FTD; F, female; FH, family history; FTD, frontotemporal dementia; FTLD: frontotemporal lobar degeneration; GnomAD NFE_MAF, minor allele frequency in the NFE population from the Genome Aggregation Database; LMN, lower motor neuron; M, male; MND, motor neuron disease; NFE, non-Finnish European; nfcPPA, non-fluent variant of PPA; PPA, primary progressive aphasias; PDB, Paget’s disease of bone; SP_MAF, aggregated minor allele frequency from Dopazo et al and the 1000 Genomes Project Consortium Spanish individuals; SOO, site of onset; UMN, upper motor neuron.