Table 5.
Specific mutations associated with Parkinsonism in FTD and their characteristic clinical phenotype.
| Gene | C9ORF72 | CHMP2B | TARDBP | VCP | FUS | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Amino acid change | NA | N143S* | A382T | K263E | N267S | A315E | R159C | R191Q | T262A | P137L | R191G | R159C | M254V* | R521C |
| Mutation type | G4C2 hexanucleotide repeat expansion | Point | Point | Point | Point | Point | Point | Point | Point | Point | Point | Point | Point | Point |
| Genomic region | NA | Exon 5 | Exon 6 | Exon 6 | Exon 6 | Exon 6 | Exon 5 | Exon 5 | Exon 5 | Exon 4 | Exon 5 | Exon 5 | Exon 6 | Exon 15 |
| AAO (years) | 58.0 | 71 | 53 | 35 | 69–74 | 57–63 | 53–62 | 37–63 | 51–56 | 38–50 | 42–45 | 50–73 | 52 | NA |
| DD (years) | 5.3 | 9 | 4 | 2 | NA | 4–6 | 1–5 | 1–7 | 4–15 | 10–21 | 9 | 5 | NA | NA |
| Parkinsonism | ++ | + | +++ | + | + | + | + | + | + | + | ++ | + | + | + |
| Personality changes | +++ | + | + | + | ++ | − | + | + | + | + | − | + | + | − |
| Dementia | + | + | + | + | + | − | + | + | ++ | − | − | + | + | + |
| Language difficulties | − | + | − | − | + | − | + | + | ++ | − | − | + | − | − |
| Supranuclear gaze palsy | − | − | − | + | − | − | − | − | − | − | − | − | − | − |
| Apraxia | − | + | − | − | − | − | − | − | − | − | − | + | − | − |
| Pyramidal signs | + | + | − | − | − | ++ | +++ | + | − | +++ | − | − | ++ | |
| Amyotrophy | ++ | − | + | − | − | + | +++ | +++ | ++ | ++ | +++ | + | − | +++ |
AAO = age at onset; DD = disease duration; NA = not present/not assessed; Sub = substitution; (−) = absent; (+) = rare; (++) = present in some cases; (+++) = frequent;
*
not proven to be pathogenic; only one mutations carrier has been identified for each mutation written in Italics.