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http://purl.uniprot.org/citations/22084127http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22084127http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22084127http://www.w3.org/2000/01/rdf-schema#comment"

Background

The SQSTM1 gene encodes p62, a major pathologic protein involved in neurodegeneration.

Objective

To examine whether SQSTM1 mutations contribute to familial and sporadic amyotrophic lateral sclerosis (ALS).

Design

Case-control study.

Setting

Academic research. Patients  A cohort of 546 patients with familial (n = 340) or sporadic (n = 206) ALS seen at a major academic referral center were screened for SQSTM1 mutations.

Main outcome measures

We evaluated the distribution of missense, deletion, silent, and intronic variants in SQSTM1 among our cohort of patients with ALS. In silico analysis of variants was performed to predict alterations in p62 structure and function.

Results

We identified 10 novel SQSTM1 mutations (9 heterozygous missense and 1 deletion) in 15 patients (6 with familial ALS and 9 with sporadic ALS). Predictive in silico analysis classified 8 of 9 missense variants as pathogenic.

Conclusions

Using candidate gene identification based on prior biological knowledge and the functional prediction of rare variants, we identified several novel SQSTM1 mutations in patients with ALS. Our findings provide evidence of a direct genetic role for p62 in ALS pathogenesis and suggest that regulation of protein degradation pathways may represent an important therapeutic target in motor neuron degeneration."xsd:string
http://purl.uniprot.org/citations/22084127http://purl.org/dc/terms/identifier"doi:10.1001/archneurol.2011.250"xsd:string
http://purl.uniprot.org/citations/22084127http://purl.org/dc/terms/identifier"doi:10.1001/archneurol.2011.250"xsd:string
http://purl.uniprot.org/citations/22084127http://purl.uniprot.org/core/author"Chen W."xsd:string
http://purl.uniprot.org/citations/22084127http://purl.uniprot.org/core/author"Chen W."xsd:string
http://purl.uniprot.org/citations/22084127http://purl.uniprot.org/core/author"Shi Y."xsd:string
http://purl.uniprot.org/citations/22084127http://purl.uniprot.org/core/author"Shi Y."xsd:string
http://purl.uniprot.org/citations/22084127http://purl.uniprot.org/core/author"Yang Y."xsd:string
http://purl.uniprot.org/citations/22084127http://purl.uniprot.org/core/author"Yang Y."xsd:string
http://purl.uniprot.org/citations/22084127http://purl.uniprot.org/core/author"Yan J."xsd:string
http://purl.uniprot.org/citations/22084127http://purl.uniprot.org/core/author"Yan J."xsd:string
http://purl.uniprot.org/citations/22084127http://purl.uniprot.org/core/author"Liu E."xsd:string
http://purl.uniprot.org/citations/22084127http://purl.uniprot.org/core/author"Liu E."xsd:string
http://purl.uniprot.org/citations/22084127http://purl.uniprot.org/core/author"Donkervoort S."xsd:string
http://purl.uniprot.org/citations/22084127http://purl.uniprot.org/core/author"Donkervoort S."xsd:string
http://purl.uniprot.org/citations/22084127http://purl.uniprot.org/core/author"Siddique T."xsd:string
http://purl.uniprot.org/citations/22084127http://purl.uniprot.org/core/author"Siddique T."xsd:string
http://purl.uniprot.org/citations/22084127http://purl.uniprot.org/core/author"Deng H.X."xsd:string
http://purl.uniprot.org/citations/22084127http://purl.uniprot.org/core/author"Deng H.X."xsd:string
http://purl.uniprot.org/citations/22084127http://purl.uniprot.org/core/author"Ajroud-Driss S."xsd:string
http://purl.uniprot.org/citations/22084127http://purl.uniprot.org/core/author"Ajroud-Driss S."xsd:string
http://purl.uniprot.org/citations/22084127http://purl.uniprot.org/core/author"Fecto F."xsd:string
http://purl.uniprot.org/citations/22084127http://purl.uniprot.org/core/author"Fecto F."xsd:string
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