New V272A presenilin 1 mutation with very early onset subcortical dementia and parkinsonism

Jiménez‐Escrig, Adriano; Rábano, Alberto; Guerrero, Carmen; Simon, Jason S.; Barquero, María Sagrario; Güell, I.; Ginestal, R; Montero, Trinidad; Orensanz, L.

doi:10.1111/j.1468-1331.2004.00865.x

Cited by 42 publications

(33 citation statements)

References 27 publications

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“…In contrast, relative preservation of naming has been noted in M139V [51, 97,178] and L153V [79]. A subcortical pattern of neuropsychological deficits was noted in V272A [81].…”

Section: Neuropsychological Profilementioning

confidence: 95%

“…LB were not seen in specimens from E120K, M139I, I143F, M146I, and H163R although only limited material was available for examination in many of these cases, often just a middle frontal gyrus [101]. LB have also been observed in L153V [79], G217D [163], M233V [70,136], and V272A [81]. LB were not observed in a patient with F105L whose clinical phenotype included parkinsonism [49] although it is not clear whether α-synuclein immunohistochemistry was performed.…”

Section: Cortical Lewy Bodies (Lb)mentioning

confidence: 98%

“…Neuropathological involvement of the basal ganglia and/or brainstem has been reported in insF1 (striatum) [121], G217D [163], M233V (striatum, pallidum) [70,136], V261F [48], V272A [81], and E280Q [141].…”

Section: Basal Ganglia Brainstemmentioning

confidence: 99%

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Clinical phenotypic heterogeneity of Alzheimer's disease associated with mutations of the presenilin–1 gene

2005

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It is now 10 years since the first report of mutations in the presenilin genes that were deterministic for familial autosomal dominant Alzheimer's disease. The most common of these mutations occurs in the presenilin-1 gene (PSEN1) located on chromosome 14. In the ensuing decade, more than 100 PSEN1 mutations have been described. The emphasis of these reports has largely been on the novelty of the mutations and their potential pathogenic consequences rather than detailed clinical, neuropsychological, neuroimaging and neuropathological accounts of patients with the mutation. This article reviews the clinical phenotypes of reported PSEN1 mutations, emphasizing their heterogeneity, and suggesting that other factors, both genetic and epigenetic,must contribute to disease phenotype.

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“…In contrast, relative preservation of naming has been noted in M139V [51, 97,178] and L153V [79]. A subcortical pattern of neuropsychological deficits was noted in V272A [81].…”

Section: Neuropsychological Profilementioning

confidence: 95%

Section: Cortical Lewy Bodies (Lb)mentioning

confidence: 98%

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Clinical phenotypic heterogeneity of Alzheimer's disease associated with mutations of the presenilin–1 gene

2005

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“…18,19 Newly identified syndromes with frontal-subcortical dementia are the Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS), 20 a novel missense mutation (V272A) of the presenilin 1 gene (PSEN1), 21 an irreversible frontal-subcortical dementia following highaltitude illness, 22 a recombinant interferon-␣-induced frontalsubcortical dementia, 23,24 pernicious anemia, 25 and type II schizophrenia. 26 These diseases may have pathologic changes extending beyond the subcortical regions to involve the cerebral cortex.…”

mentioning

confidence: 99%

Frontal-Subcortical Dementias

Bonelli¹,

Cummings²

2008

The Neurologist

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Frontal-subcortical dementias are a heterogeneous group of disorders that share primary pathology in subcortical structure and a characteristic pattern of neuropsychologic impairment. Their clinical presentation is characterized by memory disorders, an impaired ability to manipulate acquired knowledge, important changes of personality (apathy, inertia, or depression), and slowed thought processes (or bradyphrenia). It also has marked frontal dysfunction. Classic frontal-subcortical dementias include Huntington chorea, Parkinson disease dementia, progressive supranuclear palsy, thalamic degeneration, subcortical vascular dementia, multiple sclerosis, the acquired immunodeficiency syndrome dementia complex, depressive pseudodementia, and some other rare dementias like spinocerebellar degenerative syndromes, Hallervorden-Spatz disease, choreoacanthocytosis, idiopathic basal ganglia calcification, Guamanian parkinsonism-dementia complex, corticobasal degeneration multiple system atrophy, Wilson disease, metachromatic leukodystrophy, adrenoleukodystrophy, hypoparathyroidism, sarcoidosis, and other CNS inflammatory disorders. Anatomic data suggest that the frontal signs result from a disconnection of the frontal cortex from the basal ganglia. However, most frontal-subcortical dementias show cortical atrophy in later stages, and cortical dementias have subcortical pathology at some point. In fact, the concept might be seen as a continuum, and only the 2 extremes would be represented by pure cortical or subcortical pathology. Anyway, subcortical disorders may still be more similar to one another than they are to AD. Possibly, frontal-subcortical and cortical dementias are the description of the prior main target of the disease process, ending up in both cases in a global dementia. Although the dichotomy cortical versus frontal-subcortical dementia is not strict, the 2 concepts still seem to have advantages.

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“…Familial AD typically presents with early impairment of episodic memory [7]. However, certain PSEN1 mutations have been associated with atypical phenotypes including spastic paraparesis [8,9,10], speech production deficits [11], and frontal behavioral disturbances [12]. Furthermore, several studies have reported mutations in PSEN1 in cases with frontotemporal lobar degeneration (FTLD).…”

Section: Introductionmentioning

confidence: 99%

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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New V272A presenilin 1 mutation with very early onset subcortical dementia and parkinsonism

Cited by 42 publications

References 27 publications

Clinical phenotypic heterogeneity of Alzheimer's disease associated with mutations of the presenilin–1 gene

Clinical phenotypic heterogeneity of Alzheimer's disease associated with mutations of the presenilin–1 gene

Frontal-Subcortical Dementias

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

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