Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early-onset Alzheimer's disease (EOAD) and frontotemporal dementia (FTD) have a high proportion of genetically determined cases. Next-generation sequencing technologies have triggered the discovery of new mutations and genetic variants in dementia-causal genes. We performed whole-exome sequencing and selective analysis of known genes causative of EOAD and FTD in a well-characterized Spanish cohort of 103 patients (60 EOAD, 43 FTD) to find genetic variants associated to patients' phenotype. In EOAD patients, a new likely pathogenic variant in PSEN1 gene (p.G378R) was found. In FTD patients, 2 likely pathogenic variants were found, one in MAPT gene (p.P397S) and one in VCP gene (p.R159H). In our series, 2% of early-onset dementia without criteria for clinical genetic testing according to current guidelines presented a likely pathogenic mutation. We have also detected 13 additional variants of uncertain significance in causal genes, as well as rare variants in risk genes for dementia (ABCA7, SORL1, SQSTM1, and TREM2). Next-generation technologies in neurodegenerative diseases constitute a powerful tool that significantly contributes to patients' diagnosis.
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PMID:Screening of dementia genes by whole-exome sequencing in Spanish patients with early-onset dementia: likely pathogenic, uncertain significance and risk variants. 3231 27

Frontotemporal dementia (FTD) presents with a wide variability in clinical syndromes, genetic etiologies, and underlying pathologies. Despite the discovery of pathogenic variants in several genes, many familial cases remain unsolved. In a large FTD cohort of 198 familial patients, we aimed to determine the types and frequencies of variants in genes related to FTD. Pathogenic or likely pathogenic variants were revealed in 74 (37%) patients, including 4 novel variants. The repeat expansion in C9orf72 was most common (21%), followed by variants in MAPT (6%), GRN (4.5%), and TARDBP (3.5%). Other pathogenic variants were found in VCP, TBK1, PSEN1, and a novel homozygous variant in OPTN. Furthermore, we identified 15 variants of uncertain significance, including a promising variant in TUBA4A and a frameshift in VCP, for which additional research is needed to confirm pathogenicity. The patients without identified genetic cause demonstrated a wide clinical and pathological variety. Our study contributes to the clinical characterization of the genetic subtypes and confirms the value of whole-exome sequencing in identifying novel genetic variants.
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PMID:Underlying genetic variation in familial frontotemporal dementia: sequencing of 198 patients. 3284 52

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) have a strong clinical, genetic and pathological overlap. This review focuses on the current understanding of structural, functional and molecular neuroimaging signatures of genetic FTD and ALS. We overview quantitative neuroimaging studies on the most common genes associated with FTD (MAPT, GRN), ALS (SOD1), and both (C9orf72), and summarize visual observations of images reported in the rarer genes (CHMP2B, TARDBP, FUS, OPTN, VCP, UBQLN2, SQSTM1, TREM2, CHCHD10, TBK1).
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PMID:Neuroimaging in genetic frontotemporal dementia and amyotrophic lateral sclerosis. 3289 Jul 71


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