Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders.
Science
; 343(6170): 506-511, 2014 Jan 31.
Article
em En
| MEDLINE
| ID: mdl-24482476
ABSTRACT
Hereditary spastic paraplegias (HSPs) are neurodegenerative motor neuron diseases characterized by progressive age-dependent loss of corticospinal motor tract function. Although the genetic basis is partly understood, only a fraction of cases can receive a genetic diagnosis, and a global view of HSP is lacking. By using whole-exome sequencing in combination with network analysis, we identified 18 previously unknown putative HSP genes and validated nearly all of these genes functionally or genetically. The pathways highlighted by these mutations link HSP to cellular transport, nucleotide metabolism, and synapse and axon development. Network analysis revealed a host of further candidate genes, of which three were mutated in our cohort. Our analysis links HSP to other neurodegenerative disorders and can facilitate gene discovery and mechanistic understanding of disease.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tratos Piramidais
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Paraplegia Espástica Hereditária
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Doença dos Neurônios Motores
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Estudos de Associação Genética
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Exoma
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Neurônios
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos