Defining neurodegeneration on Guam by targeted genomic sequencing.
Ann Neurol
; 77(3): 458-68, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25558820
ABSTRACT
OBJECTIVE:
Amyotrophic lateral sclerosis/parkinsonism-dementia complex has been described in Guam, Western Papua, and the Kii Peninsula of Japan. The etiology and pathogenesis of this complex neurodegenerative disease remains enigmatic.METHODS:
In this study, we have used targeted genomic sequencing to evaluate the contribution of genetic variability in the pathogenesis of amyotrophic lateral sclerosis, parkinsonism, and dementia in Guamanian Chamorros.RESULTS:
Genes previously linked to or associated with amyotrophic lateral sclerosis, parkinsonism, dementia, and related neurodegenerative syndromes were sequenced in Chamorro subjects living in the Mariana Islands. Homozygous PINK1 p.L347P, heterozygous DCTN1 p.T54I, FUS p.P431L, and HTT (42 CAG repeats) were identified as pathogenic mutations.INTERPRETATION:
The findings explain the clinical, pathologic, and genetic heterogeneity observed in some multi-incident families and contribute to the excess incidence of neurodegeneration previously reported on Guam.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
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Proteínas Quinases
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Demência
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Proteína FUS de Ligação a RNA
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Esclerose Lateral Amiotrófica
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Proteínas Associadas aos Microtúbulos
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Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Aged80
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article