TYROBP genetic variants in early-onset Alzheimer's disease

Pottier, Cyril; Ravenscroft, Thomas A.; Brown, Patricia E.; Finch, Ni Cole A.; Baker, Matt; Parsons, Meeia; Asmann, Yan W.; Ren, Yingxue; Christopher, Elizabeth; Levitch, Denise; Blitterswijk, Marka van; Cruchaga, Carlos; Campion, Dominique; Nicolas, Gaël; Richard, Anne; Guerreiro, Rita; Brás, José; Züchner, Stephan; Gonzalez, Michael; Bu, Guojun; Younkin, Steven G.; Knopman, David S.; Josephs, Keith A.; Parisi, Joseph E.; Petersen, Ronald C.; Ertekin-Taner, Nilüfer; Graff‐Radford, Neill R.; Boeve, Bradley F.; Dickson, Dennis W.; Rademakers, Rosa

doi:10.1016/j.neurobiolaging.2016.07.028

Cited by 79 publications

(69 citation statements)

References 34 publications

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“…Unfortunately, patients with NHD usually perish in their 4th to 5th decades of life [67,68]. Recent studies have suggested that heterozygous gene dosage for TREM2 variants that cause NHD in homozygous carriers may confer increased AD risk [43,49,50], and also that rare coding variants of TYROBP may give rise to early-onset AD in an autosomal dominant manner [69].…”

Section: Box 1 Plaque-associated Myeloid Cells: Identity and Impactmentioning

confidence: 99%

TREM2, Microglia, and Neurodegenerative Diseases

Yeh¹,

Hansen²,

Sheng³

2017

Trends in Molecular Medicine

335

271

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Section: Box 1 Plaque-associated Myeloid Cells: Identity and Impactmentioning

confidence: 99%

TREM2, Microglia, and Neurodegenerative Diseases

Yeh¹,

Hansen²,

Sheng³

2017

Trends in Molecular Medicine

335

271

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“…Furthermore, the clinical features of AD are similar to that of other neurodegenerative diseases, such as FTLD and Parkinson's disease (PD), which might easily lead to misdiagnosis (Piccoli et al, 2016). In the present study, due to the clinical and genetic diversity of AD patients, we screened PSEN1, PSEN2, MAPT, and APP genes in 83 sporadic AD patients, while 53 dementia-related genes which were screened based on previous studies (He et al, 2017;Hooli et al, 2014;Pottier et al, 2016;Vardarajan et al, 2015) and databases such as OMIM (http://www.omim.org/), Orphanet (http://www. orpha.net/consor/cgi-bin/index.php?lng=EN), and HGMD (http:// www.hgmd.cf.ac.uk/ac/index.php) in 25 AD patients with a dementia family history.…”

Section: Introductionmentioning

confidence: 98%

Gene mutations in a Han Chinese Alzheimer's disease cohort

Zhang

Shi

et al. 2018

Brain and Behavior

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ObjectiveAlzheimer's disease (AD) is the most common form of dementia characterized by memory loss at disease onset. The gene mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the frequent causes of AD. However, the clinical and genetic features of AD overlap with other neurodegenerative diseases. The present study aimed to identify the clinical and genetic characteristics in a Han Chinese AD cohort.MethodsDetailed clinical assessment was applied to all the patients. We screened amyloid precursor protein (APP), PSEN1, PSEN2, and microtubule‐associated protein tau (MAPT) genes were assessed in 83 sporadic AD patients by Sanger sequencing. A total of 25 probands from families with AD were subjected to next‐generation sequencing on 53 dementia‐associated genes to capture the target region, and Sanger sequencing was used to detect the variants in the DNA sequence.Results PSEN1 p.L226R was found in an early‐onset AD (EOAD) family characterized by language impairment at disease onset, a novel probably pathogenetic variant (p.D534H) was identified in a frontal‐temporal dementia gene, TANK‐binding kinase 1 (TBK1) with a typical AD phenotype in a late‐onset AD (LOAD) family, and a PSEN2p.H169N mutation and two benign MAPT (p.Q230R and p.V48L) mutations were detected in three EOAD patients.ConclusionsThus, five variants were identified in a Han Chinese cohort. In the present study, a novel, probably damaging FTLD gene TBK1variant with a typical AD phenotype was detected. Also, the phenotypic characteristics of PSEN1 p.L226R, a PSEN2pathogenic mutation, and two likely benign MAPT variants were described. Hence, screening for mutations in other dementia genes could be further explored in clinically diagnosed AD patients.

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“…Three individuals were found to be carriers of the missense p.Val55Leu. This variant was previously found in a patient with early-onset Alzheimer’s disease also carrying the p.Gly2Glu and to be absent in control population (Pottier et al, 2016). The global allelic frequency of p.Val55Leu in the general population is 0.015, being more frequent in the Asian population.…”

Section: Discussionmentioning

confidence: 55%

“…More recently, an enrichment of TYROBP rare variants was reported in patients with early-onset Alzheimer’s disease (Pottier et al, 2016), and increased mRNA expression levels of TYROBP were found in the brain of LOAD patients (Zhang et al, 2013). …”

Section: Introductionmentioning

confidence: 99%

Mutations in TYROBP are not a common cause of dementia in a Turkish cohort

Darwent

Carmona

Lohmann

et al. 2017

Neurobiology of Aging

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Mutations in TYROBP and TREM2 have been shown to cause polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy. Recently, variants in TREM2 were also associated with frontotemporal dementia and Alzheimer’s disease. Given the functional proximity between these 2 genes, we investigated the genetic variation of TYROBP in a Turkish cohort of 103 dementia patients. No mutations or copy number variants predicted to be pathogenic were identified. These results indicate that mutations in TYROBP are not a common cause of dementia in this Turkish cohort.

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TYROBP genetic variants in early-onset Alzheimer's disease

Cited by 79 publications

References 34 publications

TREM2, Microglia, and Neurodegenerative Diseases

TREM2, Microglia, and Neurodegenerative Diseases

Gene mutations in a Han Chinese Alzheimer's disease cohort

Mutations in TYROBP are not a common cause of dementia in a Turkish cohort

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