Title
|
|
|
|
A Belgian ancestral haplotype harbours a highly prevalent mutation for 17q21-linked tau-negative FTLD
| |
Author
|
|
|
|
| |
Abstract
|
|
|
|
Among patients with frontotemporal lobar degeneration (FTLD), the respective frequencies of dominant 17q21-linked tau-negative FTLD (with unidentified molecular defect) and 17q21-linked tau-positive FTLD (due to MAPT mutations) remain unknown. Here, in a series of 98 genealogically unrelated Belgian FTLD patients, we identified an ancestral 8 cM MAPT containing haplotype in two patients belonging to multiplex families DR2 and DR8, without demonstrable MAPT mutations, in which FTLD was conclusively linked to 17q21 [maximum summed log of the odds (LOD) score of 5.28 at D17S931]. Interestingly, the same DR2-DR8 ancestral haplotype was observed in five additional familial FTLD patients, indicative of a founder effect. In the FTLD series, the DR2-DR8 ancestral haplotype explained 7% (7 out of 98) of FTLD and 17% (7 out of 42) of familial FTLD and was seven times more frequent than MAPT mutations (1 out of 98 or 1%). Clinically, DR2-DR8 haplotype carriers presented with FTLD often characterized by language impairment, and in one carrier the neuropathological diagnosis was FTLD with rare tau-negative ubiquitin-positive inclusions. Together, these results strongly suggest that the DR2-DR8 founder haplotype at 17q21 harbours a tau-negative FTLD causing mutation that is a much more frequent cause of FTLD in Belgium than MAPT mutations. |
| |
Language
|
|
|
|
English
| |
Source (journal)
|
|
|
|
Brain. - London
| |
Publication
|
|
|
|
London
:
2006
| |
ISSN
|
|
|
|
0006-8950
| |
DOI
|
|
|
|
10.1093/BRAIN/AWL029
| |
Volume/pages
|
|
|
|
129
:4
(2006)
, p. 841-852
| |
ISI
|
|
|
|
000236252200005
| |
Full text (Publisher's DOI)
|
|
|
|
| |
|