Dominant non-coding repeat expansions in human disease.
Genome Dyn
; 1: 67-83, 2006.
Article
em En
| MEDLINE
| ID: mdl-18724054
ABSTRACT
The general model that dominant diseases are caused by mutations that result in a gain or change in function of the corresponding protein was challenged by the discovery that the myotonic dystrophy type 1 mutation is a CTG expansion located in the 3' untranslated portion of a kinase gene. The subsequent discovery that a similar transcribed but untranslated CCTG expansion in an intron causes the same multisystemic features in myotonic dystrophy type 2 (DM2), along with other developments in the DM1 field, demonstrate a mechanism in which these expansion mutations cause disease through a gain of function mechanism triggered by the accumulation of transcripts containing CUG or CCUG repeat expansions. A similar RNA gain of function mechanism has also been implicated in fragile X tremor ataxia syndrome (FXTAS) and may play a role in pathogenesis of other non-coding repeat expansion diseases, including spinocerebellar ataxia type 8 (SCA8), SCA10, SCA12 and Huntington disease-like 2.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Expansão das Repetições de DNA
/
Genes Dominantes
/
Doenças Genéticas Inatas
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Genome Dyn
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos