Duplication within the SEPT9 gene associated with a founder effect in North American families with hereditary neuralgic amyotrophy.
Hum Mol Genet
; 18(7): 1200-8, 2009 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-19139049
ABSTRACT
Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant disorder associated with recurrent episodes of focal neuropathy primarily affecting the brachial plexus. Point mutations in the SEPT9 gene have been previously identified as the molecular basis of HNA in some pedigrees. However in many families, including those from North America demonstrating a genetic founder haplotype, no sequence mutations have been detected. We report an intragenic 38 Kb SEPT9 duplication that is linked to HNA in 12 North American families that share the common founder haplotype. Analysis of the breakpoints showed that the duplication is identical in all pedigrees, and molecular analysis revealed that the duplication includes the 645 bp exon in which previous HNA mutations were found. The SEPT9 transcript variants that span this duplication contain two in-frame repeats of this exon, and immunoblotting demonstrates larger molecular weight SEPT9 protein isoforms. This exon also encodes for a majority of the SEPT9 N-terminal proline rich region suggesting that this region plays a role in the pathogenesis of HNA.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neurite do Plexo Braquial
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Efeito Fundador
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Predisposição Genética para Doença
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Duplicação Gênica
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GTP Fosfo-Hidrolases
Tipo de estudo:
Risk_factors_studies
Limite:
Female
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Humans
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Male
País como assunto:
America do norte
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article