ATXN2 is a modifier of phenotype in ALS patients of Sardinian ancestry

Borghero, Giuseppe; Pugliatti, Maura; Marrosu, Francesco; Marrosu, Maria Giovanna; Murru, Maria Rita; Floris, Gianluca; Cannas, Antonino; Parish, Leslie D.; Cau, Tea B.; Loi, Daniela; Ticca, Anna; Traccis, S.; Manera, Umberto; Canosa, Antonio; Moglia, Cristina; Calvo, Andrea; Barberis, Marco; Brunetti, Maura; Renton, Alan E.; Nalls, Mike A.; Traynor, Bryan J.; Restagno, Gabriella; Chiò, Adriano

doi:10.1016/j.neurobiolaging.2015.06.013

Cited by 24 publications

(22 citation statements)

References 17 publications

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“…Also, the presence of at least 1 minor allele of the rs3011225 SNP located on chromosome 1p34.1 was associated with earlier age of onset in a meta‐analysis of 13 GWAS cohorts . Finally, the presence of an intermediate CAG repeat expansion in the ATXN2 gene not only is a risk factor for ALS but also is associated with a spinal phenotype and reduces survival by 1 year …”

Section: Discussionmentioning

confidence: 98%

“…29 Finally, the presence of an intermediate CAG repeat expansion in the ATXN2 gene not only is a risk factor for ALS 24 but also is associated with a spinal phenotype and reduces survival by 1 year. 30,31 In summary, we used a large population-based cohort of ALS patients to show that functional variants of the CX3CR1 gene potentially influence ALS survival. A limitation of our study is that it is based on a candidate-gene approach.…”

Section: Discussionmentioning

confidence: 99%

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Common polymorphisms of chemokine (C‐X3‐C motif) receptor 1 gene modify amyotrophic lateral sclerosis outcome: A population‐based study

et al. 2017

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Common polymorphisms of chemokine (C‐X3‐C motif) receptor 1 gene modify amyotrophic lateral sclerosis outcome: A population‐based study

et al. 2017

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“… 82 This finding is supported by an Italian study, where additionally <31 repeats were associated with spinal onset ALS and a shorter survival. 83 …”

Section: Other Rna-processing Genes Associated With Alsmentioning

confidence: 99%

The genetics of amyotrophic lateral sclerosis: current insights

Sultan

Waller

Heath

et al. 2016

DNND

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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that results in loss of the upper and lower motor neurons from motor cortex, brainstem, and spinal cord. While the majority of cases are sporadic, approximately 10% show familial inheritance. ALS is usually inherited in an autosomal dominant manner, although autosomal recessive and X-linked inheritance do occur. To date, 24 of the genes at 26 loci have been identified; these include loci linked to ALS and to frontotemporal dementia-ALS, where family pedigrees contain individuals with frontotemporal dementia with/without ALS. The most commonly established genetic causes of familial ALS (FALS) to date are the presence of a hexanucleotide repeat expansion in the C9ORF72 gene (39.3% FALS) and mutation of SOD1, TARDBP, and FUS, with frequencies of 12%–23.5%, 5%, and 4.1%, respectively. However, with the increasing use of next-generation sequencing of small family pedigrees, this has led to an increasing number of genes being associated with ALS. This review provides a comprehensive review on the genetics of ALS and an update of the pathogenic mechanisms associated with these genes. Commonly implicated pathways have been established, including RNA processing, the protein degradation pathways of autophagy and ubiquitin–proteasome system, as well as protein trafficking and cytoskeletal function. Elucidating the role genetics plays in both FALS and sporadic ALS is essential for understanding the subsequent cellular dysregulation that leads to motor neuron loss, in order to develop future effective therapeutic strategies.

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“…Some genes are not only risk factors, but they may also be survival modifiers. Several studies have shown that UNC13A [3,57,58,] and ATXN2 [59,60,61] are associated with shorter survival in ALS. The type of mutation lying in the TARDBP super rich glycine-residue domain was associated with the worst survival [62 ].…”

Section: Reviewmentioning

confidence: 99%

The modifiers of amyotrophic lateral sclerosis survival and clinical trial design

Zhou¹

2016

J Transl Sci

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Amyotrophic lateral sclerosis (ALS) patients with different median survival also show a different progression speed. Genetic studies identified several genes associated with an increased risk and/or shorter survival of ALS. In the present review, we discuss some issues critical for the definition of survival and identification of prognostic factors of ALS. More studies are needed to exclude confounds and find the true intrinsic risk factors affecting the disease onset and/or the prognosis of this disease. We propose that some mutated genes may act more as survival modifiers than as risk factors. Recruiting a homogeneous group of patients based on their genetic background is another approach that should be considered when drafting the inclusion criteria during the trial design. This approach may facilitate the development of therapies for ALS.

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ATXN2 is a modifier of phenotype in ALS patients of Sardinian ancestry

Cited by 24 publications

References 17 publications

Common polymorphisms of chemokine (C‐X3‐C motif) receptor 1 gene modify amyotrophic lateral sclerosis outcome: A population‐based study

Common polymorphisms of chemokine (C‐X3‐C motif) receptor 1 gene modify amyotrophic lateral sclerosis outcome: A population‐based study

The genetics of amyotrophic lateral sclerosis: current insights

The modifiers of amyotrophic lateral sclerosis survival and clinical trial design

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