TREM2 mutations are rare in a French cohort of patients with frontotemporal dementia

Lattante, Serena; Ber, Isabelle Le; Camuzat, Agnès; Dayan, Sarah; Godard, C; Bortel, Inge Van; Septenville, Anne de; Ciura, Sorana; Brice, Alexis; Kabashi, Edor

doi:10.1016/j.neurobiolaging.2013.04.030

Cited by 35 publications

(31 citation statements)

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“…In a large cohort of AD and FTD patients from Spanish origin, the rs75932628 variant contributed to the risk of AD, but was not harbored by any of the FTD patients [12]. Moreover, this variant was not identified in patients with early-onset FTD in the French population [21]. In addition, ALS and certain types of FTD are believed to be part of the same disease spectrum.…”

Section: Discussionmentioning

confidence: 97%

Assessment of TREM2 rs75932628 association with amyotrophic lateral sclerosis in a Chinese population

Chen¹,

Chen²,

Wei

et al. 2015

Journal of the Neurological Sciences

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Section: Discussionmentioning

confidence: 97%

Assessment of TREM2 rs75932628 association with amyotrophic lateral sclerosis in a Chinese population

Chen¹,

Chen²,

Wei

et al. 2015

Journal of the Neurological Sciences

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“…This is supported by a recent study showing that TREM2 R47H and TREM2 R62H are associated with AD risk (Cuyvers et al, 2014). Several studies also suggest that TREM2 R47H could be associated with Parkinson’s disease, frontotemporal dementia and amyotrophic lateral sclerosis (Guerreiro et al, 2013c; Lattante et al, 2013; Rayaprolu et al, 2013) but this remains controversial. In previous studies, rare homozygous loss-of-function mutations in TREM2 were associated with an autosomal recessive form of early-onset dementia, Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) (Paloneva et al, 2003).…”

Section: Sequencing Studiesmentioning

confidence: 99%

Alzheimer’s Disease Genetics: From the Bench to the Clinic

Karch

Cruchaga

Goate

2014

Neuron

410

308

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Alzheimer’s disease (AD) is a clinically heterogeneous neurodegenerative disease with a strong genetic component. Several genes have been associated with AD risk for nearly twenty years. However, it was not until the recent technological advances that allow for the analysis of millions of polymorphisms in thousands of subjects that we have been able to advance our understanding of the genetic complexity of AD susceptibility. Genome wide association studies and whole exome and whole genome sequencing have revealed more than twenty loci associated with AD risk. These studies have provided insights into the molecular pathways that are altered in AD pathogenesis, which have, in turn, provided insight into novel therapeutic targets.

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“…Patients with FTD were previously screened for mutations in FTD and ALS genes (PGRN, MAPT, C9orf 72, VCP, CHMP2B, PFN1, UBQLN2, SQSTM1, TARDBP, FUS/TLS, SOD1, ANG, TREM2), [5][6][7][8][9][10] and only patients who were found to be negative for known mutations (except for C9orf72) were included in this study. Patients with PSP were assessed for variants in MAPT, PGRN, and C9orf72.…”

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confidence: 99%

Contribution of ATXN2 intermediary polyQ expansions in a spectrum of neurodegenerative disorders

et al. 2014

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Objective: The aim of this study was to establish the frequency of ATXN2 polyglutamine (polyQ) expansion in large cohorts of patients with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP), and to evaluate whether ATXN2 could act as a modifier gene in patients carrying the C9orf72 expansion.Methods: We screened a large cohort of French patients (1,144 ALS, 203 FTD, 168 FTD-ALS, and 109 PSP) for ATXN2 CAG repeat length. We included in our cohort 322 carriers of the C9orf72 expansion (202 ALS, 63 FTD, and 57 FTD-ALS).Results: We found a significant association with intermediate repeat size ($29 CAG) in patients with ALS (both familial and sporadic) and, for the first time, in patients with familial FTD-ALS. Of interest, we found the co-occurrence of pathogenic C9orf72 expansion in 23.2% of ATXN2 intermediate-repeat carriers, all in the FTD-ALS and familial ALS subgroups. In the cohort of C9orf72 carriers, 3.1% of patients also carried an intermediate ATXN2 repeat length. ATXN2 repeat lengths in patients with PSP and FTD were found to be similar to the controls.Conclusions: ATXN2 intermediary repeat length is a strong risk factor for ALS and FTD-ALS.Furthermore, we propose that ATXN2 polyQ expansions could act as a strong modifier of the FTD phenotype in the presence of a C9orf72 repeat expansion, leading to the development of clinical signs featuring both FTD and ALS. Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are considered part of a spectrum of neurologic diseases because they share pathologic hallmarks, consisting of TAR DNA-binding protein 43 (TDP-43) pathology, and a similar genetic background, including C9orf72 expansion. On the other hand, FTD shares a prominent frontal cognitive syndrome and parkinsonism signs with progressive supranuclear palsy (PSP). Spinocerebellar ataxia type 2 (SCA2), characterized by cerebellar ataxia, parkinsonism, and mild dementia, is caused by an expanded CAG trinucleotide repeat encoding for a polyglutamine (polyQ) tract in ataxin-2 protein (ATXN2; OMIM: *601517). A link between SCA2 and ALS was established in 2010, when ATXN2 intermediate-length expansions were found to be significantly associated with ALS and it was shown that ATXN2 protein modifies TDP-43 toxicity.1 In this study, we analyzed the size of ATXN2 repeats in a large French cohort of 1,624 patients with ALS, FTD, FTD-ALS, and PSP to evaluate the exact contribution of the ATXN2 repeat size to

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TREM2 mutations are rare in a French cohort of patients with frontotemporal dementia

Cited by 35 publications

References 0 publications

Assessment of TREM2 rs75932628 association with amyotrophic lateral sclerosis in a Chinese population

Assessment of TREM2 rs75932628 association with amyotrophic lateral sclerosis in a Chinese population

Alzheimer’s Disease Genetics: From the Bench to the Clinic

Contribution of ATXN2 intermediary polyQ expansions in a spectrum of neurodegenerative disorders

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