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BACKGROUND Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9ORF72) are the most common known genetic cause of frontotemporal dementia (FTD) and motor neuron disease (MND). We assessed whether expansion size is associated with disease severity or phenotype. METHODS We did a cross-sectional Southern blot characterisation study(More)
Frontotemporal lobar degeneration with TAR DNA-binding protein 43 inclusions (FTLD-TDP) is the most common pathology associated with frontotemporal dementia (FTD). Repeat expansions in chromosome 9 open reading frame 72 (C9ORF72) and mutations in progranulin (GRN) are the major known genetic causes of FTLD-TDP; however, the genetic etiology in the majority(More)
OBJECTIVE To specify the presenting symptoms and clinical course of patients with frontotemporal dementia (FTD) and chromosome 9 open reading frame 72 (C9ORF72) repeat expansion. BACKGROUND The 2011 discovery of the C9ORF72 repeat expansion causing familial FTD and amyotrophic lateral sclerosis has permitted retrospective evaluation of potential defining(More)
Variants in transmembrane protein 106 B (TMEM106B) modify the disease penetrance of frontotemporal dementia (FTD) in carriers of progranulin (GRN) mutations. We investigated whether TMEM106B is also a genetic modifier of disease in carriers of chromosome 9 open reading frame 72 (C9ORF72) expansions. We assessed the genotype of 325 C9ORF72 expansion carriers(More)
Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9ORF72) are causative for frontotemporal dementia (FTD) and motor neuron disease (MND). Substantial phenotypic heterogeneity has been described in patients with these expansions. We set out to identify genetic modifiers of disease risk, age at onset, and survival after onset that may(More)
Repeat expansions in chromosome 9 open reading frame 72 (C9ORF72) are an important cause of both motor neuron disease (MND) and frontotemporal dementia (FTD). Currently, little is known about factors that could account for the phenotypic heterogeneity detected in C9ORF72 expansion carriers. In this study, we investigated 4 genes that could represent genetic(More)
Globular glial tauopathies (GGTs) are 4-repeat tauopathies neuropathologically characterized by tau-positive, globular glial inclusions, including both globular oligodendroglial inclusions and globular astrocytic inclusions. No mutations have been found in 25 of the 30 GGT cases reported in the literature who have been screened for mutations in microtubule(More)
The loss of chromosome 9 open reading frame 72 (C9ORF72) expression, associated with C9ORF72 repeat expansions, has not been examined systematically. Three C9ORF72 transcript variants have been described thus far; the GGGGCC repeat is located between two non-coding exons (exon 1a and exon 1b) in the promoter region of transcript variant 2 (NM_018325.4) or(More)
Mutations in the gene encoding the presenilin-1 protein (PSEN1) were first discovered to cause Alzheimer's disease (AD) 20 years ago. Since then more than 200 different pathogenic mutations have been reported, including a p.Gly206Ala founder mutation in the Hispanic population. Here we report mutation analysis of known AD genes in a cohort of 27 early-onset(More)
We aimed to identify new candidate genes potentially involved in early-onset Alzheimer's disease (EOAD). Exome sequencing was conducted on 45 EOAD patients with either a family history of Alzheimer's disease (AD, <65 years) or an extremely early age at the onset (≤55 years) followed by multiple variant filtering according to different modes of inheritance.(More)
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