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Neurogenetics
Published in: neurogenetics 3/2017

01-07-2017 | Short Communication

Rare causes of early-onset dystonia-parkinsonism with cognitive impairment: a de novo PSEN-1 mutation

Published in: Neurogenetics | Issue 3/2017

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Abstract

Mutations in PSEN1 are responsible for familial Alzheimer’s disease (FAD) inherited as autosomal dominant trait, but also de novo mutations have been rarely reported in sporadic early-onset dementia cases. Parkinsonism in FAD has been mainly described in advanced disease stages. We characterized a patient presenting with early-onset dystonia-parkinsonism later complicated by dementia and myoclonus. Brain MRI showed signs of iron accumulation in the basal ganglia mimicking neurodegeneration with brain iron accumulation (NBIA) as well as fronto-temporal atrophy. Whole exome sequencing revealed a novel PSEN1 mutation and segregation within the family demonstrated the mutation arose de novo.
We suggest considering PSEN1 mutations in cases of dystonia-parkinsonism with positive DAT-Scan, later complicated by progressive cognitive decline and cortical myoclonus even without a dominant family history.
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Literature
1.
Chen JY, Stern Y, Sano M, Mayeux R (1991) Cumulative risk of developing extrapyramidal signs, psychosis or myoclonus in the course of Alzheimer’s disease. Arch Neurol 48:1141–1143CrossRefPubMed
2.
Golan MP, Styczyńska M, Jóźwiak K et al (2004) Early-onset Alzheimer’s disease with a de novo mutation in the presenilin 1 gene. Exp Neurol 208:264–268CrossRef
3.
Dumanchin C, Brice A, Campion D et al (1998) De novo presenilin 1 mutations are rare in clinically sporadic, early onset Alzheimer’s disease cases French Alzheimer’s Disease Study Group. J Med Genet 35:672–673CrossRefPubMedPubMedCentral
4.
Devi G, Fotiou A, Jyrinji D et al (2000) Novel presenilin 1 mutations associated with early onset of dementia in a family with both early-onset and late-onset Alzheimer disease. Arch Neurol 57:1454–1457PubMed
5.
Lou F, Luo X, Li M, Ren Y, He Z (2017) Very early-onset sporadic Alzheimer’s disease with a de novo mutation in the PSEN1 gene. Neurobiol Aging 53:193.e1–193.e5CrossRef
6.
Takao M, Ghetti B, Hayakawa I et al (2002) A novel mutation (G217D) in the presenilin 1 gene (PSEN1) in a Japanese family: presenile dementia and parkinsonism are associated with cotton wool plaques in the cortex and striatum. Acta Neuropathol (Berl) 104:155–170CrossRef
7.
Jimenez-Escrig A, Rabano A, Guerrero C et al (2004) New V272A presenilin 1 mutation with very early onset subcortical dementia and parkinsonism. Eur J Neurol 11:663–669CrossRefPubMed
8.
Snider BJ, Norton J, Coats MA et al (2005) Novel presenilin 1 mutation (S170F) causing Alzheimer disease with Lewy bodies in the third decade of life. Arch Neurol 62:1821–1830CrossRefPubMed
9.
Piccini A, Zanusso G, Borghi R et al (2007) Association of a presenilin 1 S170F mutation with a novel Alzheimer disease molecular phenotype. Arch Neurol 64:738–745CrossRefPubMed
10.
Godbolt AK, Cipolotti L, Watt H, Fox NC, Janssen JC, Rossor MN (2004) The natural history of Alzheimer disease: a longitudinal presymptomatic and symptomatic study of a familial cohort. Arch Neurol 61:1743–1748CrossRefPubMed
11.
Bougea A, Koros C, Stamelou M et al (2017) Frontotemporal dementia as the presenting phenotype of p.A53T mutation carriers in the alpha-synuclein gene. Parkinsonism Relat Disord 35:82–87CrossRefPubMed
Metadata
Title
Rare causes of early-onset dystonia-parkinsonism with cognitive impairment: a de novo PSEN-1 mutation
Publication date
01-07-2017
Published in
Neurogenetics / Issue 3/2017
Print ISSN: 1364-6745
Electronic ISSN: 1364-6753
DOI
https://doi.org/10.1007/s10048-017-0518-4

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