Rapidly Progressive Frontotemporal Dementia Associated with MAPT Mutation G389R

Sun, Lin; Chen, Kathryn; Li, Xia; Xiao, Shifu

doi:10.3233/jad-160802

Cited by 11 publications

(18 citation statements)

References 27 publications

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“…Although MAPT mutations are generally thought to display complete penetrance, a recent report of the well-established p.V337M mutation (rs63750570) has described very slow disease progression in one carrier and apparent absence of disease in her 67-year-old son [15]. Relatedly, the p.G389R mutation (rs63750512) in some cases results in aggressive FTD, but it can also be found in unaffected individuals [16]. Cases such as these illustrate that even for well-characterized genes, presumed "causal" mutations may not be completely penetrant, possibly due to the modifying effects of other genetic or environmental factors.…”

Section: Mapt Grn and C9orf72mentioning

confidence: 99%

Recent Advances in the Genetics of Frontotemporal Dementia

et al. 2019

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Purpose of review: In this review we highlight recent advances in the human genetics of frontotemporal dementia (FTD). In addition to providing a broad survey of genes implicated in FTD in the last several years, we also discuss variation in genes implicated in both hereditary leukodystrophies and risk for FTD (e.g., TREM2, TMEM106B, CSF1R, AARS2, NOTCH3). Recent findings: Over the past five years, genetic variation in approximately 50 genes has been confirmed or suggested to cause or influence risk for FTD and FTD-spectrum disorders. We first give background and discuss recent findings related to C9ORF72, GRN and MAPT, the genes most commonly implicated in FTD. We then provide a broad overview of other FTD-associated genes and go on to discuss new findings in FTD genetics in East Asian populations, including pathogenic variation in CHCHD10, which may represent a frequent cause of disease in Chinese populations. Finally, we consider recent insights gleaned from genome-wide association and genetic pleiotropy studies. Summary: Recent genetic discoveries highlight cellular pathways involving autophagy, the endolysosomal system and neuroinflammation, and reveal an intriguing overlap between genes that confer risk for leukodystrophy and FTD.

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Section: Mapt Grn and C9orf72mentioning

confidence: 99%

Recent Advances in the Genetics of Frontotemporal Dementia

et al. 2019

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“…We also excluded studies that did not assess dementia or measure DNA methylation. All remaining articles (n = 48) fulfilled the following inclusion criteria: (1) DNA methylation was measured in peripheral blood and (2) compared between individuals with dementia and another group [21–68]. Included studies were published between 2008 and 2017.…”

Section: Resultsmentioning

confidence: 99%

“…One case-control study of 1177 participants involved only a subsample of participants in their analysis, but the exact number was unclear [61]. Two of the studies were cohorts (with 52 and 71 participants, respectively) [33,57], and there were two small case reports (n = 6 and 3, respectively) [66,68].…”

Section: Resultsmentioning

confidence: 99%

Blood DNA methylation as a potential biomarker of dementia: A systematic review

Fransquet

Lacaze

Saffery

et al. 2017

Alzheimer's & Dementia

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Dementia is a major public health issue with rising prevalence rates, but many individuals remain undiagnosed. Accurate and timely diagnosis is key for the optimal targeting of interventions. A noninvasive, easily measurable peripheral biomarker would have greatest utility in population-wide diagnostic screening. Epigenetics, including DNA methylation, is implicated in dementia; however, it is unclear whether epigenetic changes can be detected in peripheral tissue. This study aimed to systematically review the evidence for an association between dementia and peripheral DNA methylation. Forty-eight studies that measured DNA methylation in peripheral blood were identified, and 67% reported significant associations with dementia. However, most studies were underpowered and limited by their case-control design. We emphasize the need for future longitudinal studies on large well-characterized populations, measuring epigenetic patterns in asymptomatic individuals. A biomarker detectable in the preclinical stages of the disease would have the greatest utility in future intervention and treatment trials.

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“…The clinical and genetic features are summarized in Table 2 . 7 – 13 Seven of the ten MAPT mutations are found in “the hot spot” region of exons 9–13, with three exceptions (L48V, D177V, R5H). It was well documented that the P301L MAPT mutation was associated with mainly FTD and sometimes parkinsonism in the western population.…”

Section: Discussionmentioning

confidence: 99%

The role of <em>MAPT</em> gene in Chinese dementia patients: a P301L pedigree study and brief literature review

Chen

Xia

et al. 2018

NDT

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Background and purposeFrontotemporal dementia (FTD) is the second most common presenile dementia characterized by behavioral changes and language impairment. The diagnosis of FTD relies heavily on neuroimaging, and sometimes on genetic screening. However, the genetic components in Chinese FTD patients remain largely unknown. Only a few FTD cases with established mutations have been reported in China. This study reported the detailed clinical and neuroimaging features in a Chinese behavioral variant FTD family. The role of MAPT gene mutation in Chinese dementia patients was also reviewed.MethodsBy detailed inquiry of all affected individuals in the family, this study summarized the main clinical features of the disease. Four candidate genes (MAPT, PSEN1, PSEN2, and APP) were screened by direct sequencing. Structural magnetic resonance imaging (MRI), functional imaging of cerebral blood flow with arterial spin-labeled MRI (ASL-MRI), and cerebral metabolism with fluorodeoxyglucose positron emission tomography (FDG-PET) were collected in the proband and healthy mutation carriers.ResultsBy direct sequencing of candidate genes (MAPT, PSEN1, PSEN2, and APP), this study identified the P301L mutation in the MAPT gene in the proband and three unaffected family members. The phenotype of the affected cases was consistent within the pedigree. In this genetically proven behavioral variant FTD (bvFTD) patient, the maps of hypoperfusion on ASL-MRI look fairly similar to the hypometabolism on FDG-PET. The clinical feature for this bvFTD was in line with the hypoperfusion or hypometabolism pattern on functional neuroimagings. The phenotype of P301L in east Asia seems similar to western countries.ConclusionFor the inherited FTD patients, ASL-MRI and genetic identification were strongly recommended for the final diagnosis. In case of being underestimated, the role of MAPT gene mutation in Chinese FTD patients warrants further investigation.

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Rapidly Progressive Frontotemporal Dementia Associated with MAPT Mutation G389R

Cited by 11 publications

References 27 publications

Recent Advances in the Genetics of Frontotemporal Dementia

Recent Advances in the Genetics of Frontotemporal Dementia

Blood DNA methylation as a potential biomarker of dementia: A systematic review

The role of <em>MAPT</em> gene in Chinese dementia patients: a P301L pedigree study and brief literature review

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