Table 1.
Progranulin (GRN) genetic variants included in this study
| Cases | cDNA | Protein | Diagnosis | Tissue | References |
|---|---|---|---|---|---|
| 1, 2 | c.1252C>T | R418X | FTLD-TDP (autopsy) | Brain | [5] |
| 3 | c.1477C>T | R493X | FTLD-TDP (autopsy) | Brain | [22] |
| 4 | c.348A>C | A89VfsX139 | FTLD-TDP (autopsy) | Brain | a |
| 5 | c.911G>A | W304X | FTLD-TDP (autopsy) | Brain | [22] |
| 6b | c.1009C>T | Q337X | FTLD-TDP (autopsy) | Brain | [48] |
| c.903G>A | S301S | ||||
| c.1070C>A | P357R | ||||
| 7 | c.1179 + 2T>C | V395YfsX29 | FTLD-TDP (autopsy) | Brain | a |
| 8 | c.26C>A | A9D | FTLD-TDP (autopsy) | Brain | [22] |
| 9 | c.1414-2A>G | A472VfsX10 | FTD/PPA (clinical) | Blood | a |
| 10 | c.1317_1318delCA | D441HfsX4 | FTLD-TDP (autopsy) | Blood | a |
| 11 | c.154delA | T52HfsX2 | FTLD-TDP (autopsy) | Blood | [22] |
All variants are believed to be pathogenic. For cases 1–8, brain tissue was analyzed. For cases 9–11, peripheral blood mRNA was used. For cases 10 and 11, autopsy information subsequently became available and is shown in the table. Case 8, with the GRN variant c.26C>A, was included in protein studies only, as others have shown that this mutation may not show mRNA transcript haploinsufficiency [35]
FTLD-TDP frontotemporal lobar degeneration with TDP-43 inclusions, FTD frontotemporal dementia, PPA primary progressive aphasia
a
Yu et al. (in press) Arch Neurol
b
Case has three progranulin variations