Expanded
            <i>ATXN2</i>
            CAG repeat size in ALS identifies genetic overlap between ALS and SCA2

Damme, Philip Van; Veldink, Jan H.; Blitterswijk, Marka van; Corveleyn, Anniek; Vught, Paul W.J. van; Thijs, Vincent; Dubois, Bénédicte; Matthijs, Gert; Berg, Leonard H van den; Robberecht, Wim

doi:10.1212/wnl.0b013e31821f445b

Cited by 158 publications

(129 citation statements)

References 31 publications

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“…Intermediate-length expansions in ATXN2 are a risk factor for ALS-but, strangely enough-not for ALS-FTD or FTD 89,90 -and ATXN2 mutations can present as ALS. 91 The biological basis for the link between SCA and ALS is unknown.…”

Section: Als With Extrapyramidal Involvementmentioning

confidence: 99%

The phenotypic variability of amyotrophic lateral sclerosis

2014

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| Classic textbook neurology teaches that amyotrophic lateral sclerosis (ALS) is a degenerative disease that selectively affects upper and lower motor neurons and is fatal 3-5 years after onset-a description which suggests that the clinical presentation of ALS is very homogenous. However, clinical and postmortem observations, as well as genetic studies, demonstrate that there is considerable variability in the phenotypic expression of ALS. Here, we review the phenotypic variability of ALS and how it is reflected in familial and sporadic ALS, in the degree of upper and lower motor neuron involvement, in motor and extramotor involvement, and in the spectrum of ALS and frontotemporal dementia. Furthermore, we discuss some unusual clinical characteristics regarding presentation, age at onset and disease progression. Finally, we address the importance of this variability for understanding the pathogenesis of ALS and for the development of therapeutic strategies.

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Section: Als With Extrapyramidal Involvementmentioning

confidence: 99%

The phenotypic variability of amyotrophic lateral sclerosis

2014

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“…Many of the ADCAs in addition to limb and truncal ataxia cause dysarthria, dysphagia, and neuropathy. The clinical syndrome associated with SCA2 may include parkinsonism or motor neuron disease (amyotrophic lateral sclerosis) 10,11 Age of onset is quite variable and usually in adulthood. Disease course is also variable, although generally the disease progresses over decades.…”

Section: Types Of Hereditary Ataxiamentioning

confidence: 99%

Hereditary ataxias: overview

Jayadev

Bird

2013

Genetics in Medicine

232

172

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“…At least five patients carrying a CAG expansion in SCA2 gene have been reported with ALS‐like phenotype, with a CAG expansion ranging from 33 to 39 80, 81, 82, 83, 84. The allele was interrupted by 1 CAA in the only sequenced case 81.…”

Section: Atxn2 and Amyotrophic Lateral Sclerosis (Als)mentioning

confidence: 99%

The Multiple Faces of Spinocerebellar Ataxia type 2

Antenora

Rinaldi

Roca

et al. 2017

Ann Clin Transl Neurol

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Spinocerebellar ataxia type 2 (SCA2) is among the most common forms of autosomal dominant ataxias, accounting for 15% of the total families. Occurrence is higher in specific populations such as the Cuban and Southern Italian. The disease is caused by a CAG expansion in ATXN2 gene, leading to abnormal accumulation of the mutant protein, ataxin‐2, in intracellular inclusions. The clinical picture is mainly dominated by cerebellar ataxia, although a number of other neurological signs have been described, ranging from parkinsonism to motor neuron involvement, making the diagnosis frequently challenging for neurologists, particularly when information about the family history is not available. Although the functions of ataxin‐2 have not been completely elucidated, the protein is involved in mRNA processing and control of translation. Recently, it has also been shown that the size of the CAG repeat in normal alleles represents a risk factor for ALS, suggesting that ataxin‐2 plays a fundamental role in maintenance of neuronal homeostasis.

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Expanded ATXN2 CAG repeat size in ALS identifies genetic overlap between ALS and SCA2

Abstract: Our data reveal a novel genetic overlap between ALS and SCA2.

Cited by 158 publications

References 31 publications

The phenotypic variability of amyotrophic lateral sclerosis

The phenotypic variability of amyotrophic lateral sclerosis

Hereditary ataxias: overview

The Multiple Faces of Spinocerebellar Ataxia type 2

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