Familial Semantic Dementia with P301L Mutation in the Tau Gene

Ishizuka, Takanori; Nakamura, Masayuki; Ichiba, Mio; Sano, Akira

doi:10.1159/000328412

Cited by 26 publications

(19 citation statements)

References 80 publications

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“…In some patients (31%), the clinical onset consisted of isolated language impairment with word-finding difficulties and semantic errors, meeting the criteria for the semantic variant of PPA. Although some studies suggest that genetic mutations are not commonly associated with PPA, it is not rare that carriers of mutations in the MAPT gene present language impairment with semantic deficits at onset [17,18], suggesting that family history should be investigated in patients with the semantic variant of PPA. By contrast, PGRN mutations have been related to nonfluent or mixed PPA [7,19].…”

Section: Discussionmentioning

confidence: 99%

Frontotemporal Dementia Caused by the P301L Mutation in the MAPT Gene: Clinicopathological Features of 13 Cases from the Same Geographical Origin in Barcelona, Spain

Borrego‐Écija

Morgado

Palencia-Madrid

et al. 2017

Dement Geriatr Cogn Disord

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Background/Aims: We identified and studied 13 patients carrying the P301L mutation in the MAPT gene from the same area (Baix Llobregat County) in Barcelona, Spain. Methods: The demographic and clinical features were reviewed retrospectively. Detailed neuropathological characterization was obtained in 9 subjects. To investigate the origin of the P301L mutation in these families, 20 single nucleotide polymorphisms (SNPs) in the MAPT gene were analyzed. Results: The mean age at disease onset was 51 years and the mean disease duration was 7 years. The most common initial symptoms were behavioral changes (54%), followed by language disturbances (31%) and memory loss (15%). 46% developed parkinsonism. Neuropathology showed an extensive neuronal and glial 4-repeat (4R) tauopathy with “mini-Pick”-like bodies in the dentate gyrus as the characteristic underlying pathology in all cases. In 1 subject, additional 4R globular glial inclusions were observed. All the mutation carriers showed the same haplotype for the SNPs analyzed, suggesting a common ancestor. Conclusion: These findings suggest a relative homogeneous clinicopathological phenotype in P301L MAPT mutation carriers in our series. This phenotype might help in the differential diagnosis from other tauopathies and be a morphological hint for genetic testing. The haplotype analysis results suggest a founder effect of the P301L mutation in this area.

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Section: Discussionmentioning

confidence: 99%

Frontotemporal Dementia Caused by the P301L Mutation in the MAPT Gene: Clinicopathological Features of 13 Cases from the Same Geographical Origin in Barcelona, Spain

Borrego‐Écija

Morgado

Palencia-Madrid

et al. 2017

Dement Geriatr Cogn Disord

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“…Recently, we reported familial cases with semantic dementia possessing a P301L mutation in the tau gene [26]. Although patients with the P301L mutation usually exhibit FTLD features, our cases interestingly presented with pure semantic dementia.…”

Section: Discussionmentioning

confidence: 73%

Different Clinical Phenotypes in Siblings with a Presenilin-1 P264L Mutation

Ishizuka

Nakamura

Ichiba

et al. 2012

Dement Geriatr Cogn Disord

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Background: Mutations in the presenilin-1 gene (PSEN1) have been identified in autosomal dominant early-onset cases of Alzheimer’s disease (AD). Aims: To investigate different clinical phenotypes of siblings possessing the same heterozygous P264L mutation in the PSEN1 gene. Methods: We evaluated clinical features, neuroimaging results, and neuropsychological examinations. The PSEN1 gene and other dementia-related gene mutations were screened. Results: We clinically diagnosed the proband as atypical AD with frontotemporal dementia features and diagnosed the elder brother of the proband as typical AD, based on neuropsychological symptoms and a brain imaging examination including amyloid imaging data. A heterozygous P264L mutation in the PSEN1 gene was identified in both siblings. Conclusion: This study is one of few reports of AD siblings possessing the same mutation but exhibiting different clinical phenotypes in a Japanese family possessing a P264L mutation in the PSEN1 gene. The current results suggest that unknown modifiers, including both genetic and epigenetic factors, may alter the pathological and clinical phenotypes of a genetically predetermined disease.

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“…In Asia, MAPT mutations have been reported in familial SD (Ishizuka et al, 2011), although typically in low frequency (Wada-Isoe et al, 2012). These results suggest that genetic factors for the development of FTLD may have a less important role in the Asian population.…”

Section: F a M I L Y M E M B E R S A Ff E C T E D W I T H F A M I L Ymentioning

confidence: 94%

Family history of frontotemporal lobar degeneration in Asia – an international multi-center research

Fukuhara

Ghosh

Fuh

et al. 2014

Int. Psychogeriatr.

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Familial Semantic Dementia with P301L Mutation in the Tau Gene

Cited by 26 publications

References 80 publications

Frontotemporal Dementia Caused by the P301L Mutation in<b> </b>the<b><i> MAPT</i></b> Gene: Clinicopathological Features of 13 Cases from the Same Geographical Origin in Barcelona, Spain

Frontotemporal Dementia Caused by the P301L Mutation in<b> </b>the<b><i> MAPT</i></b> Gene: Clinicopathological Features of 13 Cases from the Same Geographical Origin in Barcelona, Spain

Different Clinical Phenotypes in Siblings with a Presenilin-1 P264L Mutation

Family history of frontotemporal lobar degeneration in Asia – an international multi-center research

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