Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an expanding polyglutamine repeat in the IT15 or huntingtin gene.
INTRODUCTION--The discovery of an expansion of a trinucleotide (CAG) repeat region in the IT15 gene on the short arm of chromosome 4 has identified the mutational mechanism causing Huntington's disease (HD) and enables the direct diagnosis of affected subjects based on DNA analysis alone.
In brain tissue from HD heterozygotes with adult onset and more clinically severe juvenile onset, where the largest expansions occur, a mutant protein of equivalent intensity to wild-type huntingtin was detected in cortical synaptosomes, indicating that a mutant species is synthesized and transported with the normal protein to nerve endings.
Both alleles of the IT15 protein were expressed at similar levels in HD lymphoblastoid cell lines and HD post-mortem hippocampus and cerebellum (regions relatively spared in HD), indicating that even very long CAG repeats can be translated into polyglutamine.
Huntington's disease (HD) is a dominant neurodegenerative disorder caused by expansion of a CAG repeat in the gene encoding huntingtin, a protein of unknown function.
Factors that determine the nature of symptoms at onset and the mode of progression of Huntington's disease seem to be operating independently of the (CAG)n trinucleotide repeat in gene IT15.
In order to determine whether the exon containing the expanded CAG repeat is present in IT-15 mRNA from HD patients, we amplified across this region and demonstrated the presence of the expanded repeat in cDNA from both striatum and cortex.
The genetic defect causing Huntington's disease (HD) has been identified as an unstable expansion of a trinucleotide (CAG) repeat sequence within the coding region of the IT15 gene on chromosome 4.
The mutation causing Huntington disease (HD) has been identified as an expansion of a polymorphic (CAG)n repeat in the 5' part of the huntingtin gene.The specific neuropathology of HD, viz. selective neuronal loss in the caudate nucleus and putamen, cannot be explained by the widespread expression of the gene.
The genetic mutation underlying Huntington's disease (HD) has been identified as an expansion and instability of a specific CAG repeat sequence in a gene (IT15) on chromosome 4.
The recent identification of the Huntington's disease (HD) gene, enabled us to synthesize oligopeptides corresponding with the carboxy-terminal end of the predicted HD-gene (IT15) product.
Analysis of the distribution of normal and expanded alleles of the polymorphic (CAG)n repeat in the IT15 gene in the Dutch population confirmed the presence of an expanded repeat on all Huntington's disease (HD) chromosomes.