Early-onset Alzheimer's disease with a de novo mutation in the presenilin 1 gene

Golan, Maciej P.; Styczyńska, Maria; Jóźwiak, Krzysztof; Walecki, Jerzy; Maruszak, Aleksandra; Pniewski, Jarosław; Ługiewicz, R.; Filipek, Sławomir; Żekanowski, Cezary; Barcikowska, Maria

doi:10.1016/j.expneurol.2007.08.016

Cited by 46 publications

(38 citation statements)

References 22 publications

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“…Observations in patients harbouring this mutation have been described - with considerable differences across reports - in consecutive publications since 2005 [41,42,43,44,45]. The most consistent findings associated with this mutation are a very early onset of dementia in the late twenties and cerebellar ataxia as a prominent non-cognitive symptom whereas the degree of variability of genotype-phenotype correlations in S170F carriers remains unclear.…”

Section: Introductionmentioning

confidence: 82%

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Phenotypic Variability in Autosomal Dominant Familial Alzheimer Disease due to the S170F Mutation of Presenilin-1

et al. 2018

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Background: In rare cases, patients with Alzheimer disease (AD) present at an early age and with a family history suggestive of an autosomal dominant mode of inheritance. Mutations of the presenilin-1 (PSEN1) gene are the most common causes of dementia in these patients. Early-onset and particularly familial AD patients frequently present with variable non-amnestic cognitive symptoms such as visual, language or behavioural changes as well as non-cognitive, e.g. motor, symptoms. Objective: To investigate the phenotypic variability in carriers of the PSEN1 S170F mutation. Methods: We report a family with 4 patients carrying the S170F mutation of whom 2 underwent detailed clinical examinations. We discuss our current findings in the context of previously reported S170F cases. Results: The clinical phenotype was consistent regarding initial memory impairment and early onset in the late twenties found in all S170F patients. There were frequent non-amnestic cognitive changes and, at early stages of the disease, indications of a more pronounced disturbance of visuospatial abilities as compared to face and object recognition. Non-cognitive symptoms most often included myoclonus and cerebellar ataxia. A review of the available case reports indicates some phenotypic variability associated with the S170F mutation including different constellations of symptoms such as parkinsonism and delusions. Conclusion: The variable clinical findings associated with the S170F mutation highlight the relevance of atypical phenotypes in the context of research and under a clinical perspective. CSF sampling and detection of Aβ species may be essential to indicate AD pathology in unclear cases presenting with cognitive and motor symptoms at a younger age.

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Section: Introductionmentioning

confidence: 82%

“…Thereupon, sequencing of PSEN1 revealed the S170F mutation, which was later confirmed in his sister (III.2). The pathogenic nature of the S170F mutation has been established before in several familial as well as sporadic cases [41,42,43,44,45]. …”

Section: Resultsmentioning

confidence: 99%

Phenotypic Variability in Autosomal Dominant Familial Alzheimer Disease due to the S170F Mutation of Presenilin-1

et al. 2018

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“…There are also some family members with the mutation p.P117A [74,75], p.P117L [76][77][78] and p.L173W [79] have recently been recorded with onset at 24 years. Very early onset of cognitive decline, before age 30 years, has been noted with the following PSEN-1 mutations: p.L85P [80], p.T116N [81][82][83][84], p.P117S [77], p.I143T [82,83,[85][86][87], InsFI [82,88], p.L166H [89], p.S169L [90,91], p.S170F [92][93][94], p.G209V [95], p.M233V [96], p.M233I [97], p.L235Pr [98], p.Y256S [99], p.A260V [39,100], p.V272A [84,101], p.L381V [102], p.G384A [85], p.L424R [103], and p.A434C [82]. PSEN-1 mutations show almost complete penetrance by the age of 60 years.…”

Section: Aao and Penetrancementioning

confidence: 99%

“…The reported families that developed myoclonus carrying the PSEN-1 mutations including p.L113Q, p.Y115H [46], p.P117R, p.H163R [101], p.S169P [122,123], p.S169L [90,91], p.S170F [94], p.L235P, p.R269H [98], p.L250V [124], and p.R269G [125]. The epilepsy/seizure-associated PSEN-1 mutations are spread throughout the PSEN-1.…”

Section: Myoclonus and Seizuresmentioning

confidence: 99%

The Correlation between Genotype and Phenotype of Alzheimer's Disease

Li¹,

Jiang²,

Wu³

2018

J Alzheimers Dis Parkinsonism

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“…Although very few studies looking for DNMs have been conducted for these diseases, some exist for Alzheimer's disease. A few reports mention the potential implication of DNMs in early-onset Alzheimer's disease, particularly in the presenilin 1 gene [14,15]. Indeed, a critical factor in evaluating the potential role of DNM in any disease may in fact be age of onset.…”

mentioning

confidence: 99%

How De Novo Mutation Studies Will Change Our View of the Genetics of Neurological and Psychiatric Disorders

Girard¹,

Rouleau

2011

Future Neurol.

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Early-onset Alzheimer's disease with a de novo mutation in the presenilin 1 gene

Cited by 46 publications

References 22 publications

Phenotypic Variability in Autosomal Dominant Familial Alzheimer Disease due to the S170F Mutation of Presenilin-1

Phenotypic Variability in Autosomal Dominant Familial Alzheimer Disease due to the S170F Mutation of Presenilin-1

The Correlation between Genotype and Phenotype of Alzheimer's Disease

How De Novo Mutation Studies Will Change Our View of the Genetics of Neurological and Psychiatric Disorders

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