Screening for C9ORF72 repeat expansion in FTLD

被引：19

作者：

Ferrari, Raffaele ^{[1
,2
]}

Mok, Kin ^{[2
]}

Moreno, Jorge H. ^{[1
]}

Cosentino, Stephanie ^{[3
]}

Goldman, Jill ^{[3
]}

Pietrini, Pietro ^{[4
]}

Mayeux, Richard ^{[3
]}

Tierney, Michael C. ^{[3
]}

Kapogiannis, Dimitrios ^{[3
,6
]}

Jicha, Gregory A. ^{[7
]}

Murrell, Jill R. ^{[8
]}

Ghetti, Bernardino ^{[8
]}

Wassermann, Eric M. ^{[5
]}

Grafman, Jordan ^{[5
,9
]}

Hardy, John ^{[2
]}

Huey, Edward D. ^{[3
,5
]}

Momeni, Parastoo ^{[1
]}

机构：

[1] Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, Neurogenet Lab, Lubbock, TX 79430 USA

[2] UCL, Inst Neurol, London, England

[3] Columbia Univ, Gertrude H Sergievsky Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10027 USA

[4] Univ Pisa, Sch Med, Lab Clin Biochem & Mol Biol, I-56100 Pisa, Italy

[5] Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bethesda, MD USA

[6] NIA, Clin Res Branch, NIH, Bethesda, MD 20892 USA

[7] Univ Kentucky, Sanders Brown Ctr Aging, Alzheimers Dis Ctr, Lexington, KY 40536 USA

[8] Indiana Univ Sch Med, Dept Pathol & Lab Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN USA

[9] Kessler Fdn Res Ctr, W Orange, NJ USA

来源：

NEUROBIOLOGY OF AGING | 2012年 / 33卷 / 08期

关键词：

FTLD; bv-FTD; FTD-ALS; C9ORF72; GRN; PSEN-2; Alzheimer's disease; AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION; HEXANUCLEOTIDE REPEAT; DIAGNOSTIC-CRITERIA; CHROMOSOME; 9P; DEMENTIA; ALS; GENE; FTD; CONSENSUS;

D O I：

10.1016/j.neurobiolaging.2012.02.017

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

In the present study we aimed to determine the prevalence of C9ORF72 GGGGCC hexanucleotide expansion in our cohort of 53 frontotemporal lobar degeneration (FTLD) patients and 174 neurologically normal controls. We identified the hexanucleotide repeat, in the pathogenic range, in 4 (2 bv-frontotemporal dementia (FTD) and 2 FTD-amyotrophic lateral sclerosis [ALS]) out of 53 patients and 1 neurologically normal control. Interestingly, 2 of the C9ORF72 expansion carriers also carried 2 novel missense mutations in GRN (Y294C) and in PSEN-2(I146V). Further, 1 of the C9ORF72 expansion carriers, for whom pathology was available, showed amyloid plaques and tangles in addition to TAR (trans-activation response) DNA-binding protein (TDP)-43 pathology. In summary, our findings suggest that the hexanucleotide expansion is probably associated with ALS, FTD, or FTD-ALS and occasional comorbid conditions such as Alzheimer's disease. These findings are novel and need to be cautiously interpreted and most importantly replicated in larger numbers of samples. Published by Elsevier Inc.

引用

页码：1850.e1 / 1850.e11

页数：11

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