Table 5.
Genetic causes in MSA, PSP, CBD and FTD
| Gene | Gene product | Clinical phenotypes |
|---|---|---|
| FTLD | ||
| MAPT | Microtubule-associated protein tau | bvFTD, navPPA, svPPA, CBS, PSP, FTDP-17, PiD |
| GRN | Progranulin | bvFTD, navPPA, svPPA, CBS, FTDP-17 |
| C9orf72 | Chromosome 9 open reading frame 72 protein | bvFTD, MND, FTD-MND, svPPA, navPPA, lvPPA, akinetic-rigid syndrome |
| CHMP2B | Chromatin-modifying protein 2Ba | bvFTD, FTD-MND |
| VCP | Valosin-containing protein | IBMPFD, FTD-MND |
| hnRNPA1 | Heterogeneous nuclear ribonucleoprotein A1 | MSP (FTD-MND) |
| hnRNPA2B1 | Heterogeneous nuclear ribonucleoprotein A2B1 | MSP (FTD-MND) |
| TARDBP | TAR DNA binding protein | MND, bvFTD, svPPA |
| FUS/TLS | Fused in sarcoma/translocated in liposarcoma protein | MND, bvFTD, FTD-MND |
| SQSTM1 | Sequestosome 1 | FTD-MND, PPA, bvFTD |
| TBK1 | TANK binding kinase 1 | bvFTD, PPA, FTD-MND |
| CHCHD10 | Coiled-coil-helix coiled-coil-helix domain-containing protein 10 | bvFTD, FTD-MND |
| TMEM106Bb,c | Transmembrane protein 106B | |
| RAB38b | Ras-related protein Rab-38 | |
| HLA-locusb | Major histocompatibility complex, class II, DR alpha / DR beta 5 | |
| MSA | ||
| COQ2d | Coenzyme Q2 | |
| SNCAb | α-synuclein | |
| PSP | ||
| MAPT | Microtubule-associated protein tau | |
| STX-6b | Syntaxin 6 | |
| EIF2AK3b | Eukaryotic translation initiation factor 2α kinase 3 | |
| CBD | ||
| SOS1b | Son of sevenless homologue 1 | |
| lnc-KIF13B-1b | Long noncoding RNA, 8p12 locus | |
| MSA, PSP, CBD | ||
| MAPT H1b | Microtubule-associated protein tau (H1 haplotype) | |
| PSP, CBD | ||
| MOBPb | Myelin-associated oligodendrocyte basic protein |
IBMPFD, inclusion body myopathy with Paget disease of the bone and frontotemporal dementia; MSP, multisystem proteinopathy; PiD, Pick’s disease.
a
Synonymous with charged multivesicular body protein 2B;
b
these genes were associated with the disorders in GWAS and are considered risk factors for sporadic disease, while mutations in the other genes listed cause familial disease;
c
TMEM106B modifies disease (FTD with TDP-43 pathology) in GRN mutation carriers;
d
COQ2 variants both confer risk in sporadic MSA patients (GWAS locus) and cause familial MSA.