Progranullin locus deletion in frontotemporal dementia

被引：79

作者：

Gijselinck, I. ^{[1
,3
]}

van der Zee, J. ^{[1
,3
]}

Engelborghs, S. ^{[4
,5
]}

Goossens, D. ^{[2
]}

Peeters, K. ^{[1
,3
]}

Mattheijssens, A. ^{[1
,3
]}

Corsmit, E. ^{[1
,3
]}

Del-Favero, J. ^{[2
]}

De Deyn, P. P. ^{[4
,5
]}

Van Broeckhoven, C. ^{[1
,3
]}

Cruts, M. ^{[1
,3
]}

机构：

[1] Univ Antwerp VIB, CBE, Dept Mol Genet, Neurodegenerat Brain Dis Grp, BE-2610 Antwerp, Belgium

[2] Univ Antwerp VIB, Appl Mol Genom Grp, Dept Mol Genet, BE-2610 Antwerp, Belgium

[3] Univ Antwerp, Inst Born Bunge, Neurogenet Lab, B-2020 Antwerp, Belgium

[4] Univ Antwerp, Inst Born Bunge, Lab Neurochem & Behav, B-2020 Antwerp, Belgium

[5] Middelheim Hosp, Div Neurol, Memory Clin, Antwerp, Belgium

来源：

HUMAN MUTATION | 2008年 / 29卷 / 01期

关键词：

progranulin; PGRN; GRN; frontotemporal dementia; haploinsufficiency;

D O I：

10.1002/humu.20651

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Ubiquitin-positive, tau-negative, frontotemporal dementia (FTD) is caused by null mutations in progranulin (PGRN; HUGO gene symbol GRN), suggesting a haploinsufficiency mechanism. Since whole gene deletions also lead to the loss of a functional allele, we performed systematic quantitative analyses of PGRN in a series of 103 Belgian FTD patients. We identified in one patient (1%) a genomic deletion that was absent in 267 control individuals. The deleted segment was between 54 and 69 kb in length and comprised PGRN and two centromeric neighboring genes RPIP8 (HUGO gene symbol RLTNDC3A) and SLC25A39. The patient presented clinically with typical FTD without additional symptoms, consistent with haploinsufficiency of PGRN being the only gene contributing to the disease phenotype. This study demonstrates that reduced PGRN in absence of mutant protein is sufficient to cause neurodegeneration and that previously reported PGRN mutation frequencies are underestimated.

引用

页码：53 / 58

页数：6

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