Genetics and Neuropathology of Huntington's Disease

Abstract

Huntington’s disease (HD) is an autosomal dominant progressive neurodegenerative disorder that prominently affects the basal ganglia, leading to affective, cognitive, behavioral and motor decline. The basis of HD is a CAG repeat expansion to >35 CAG in a gene that codes for a ubiquitous protein known as huntingtin, resulting in an expanded N-terminal polyglutamine tract. The size of the expansion is correlated with disease severity, with increasing CAG accelerating the age of onset. A variety of possibilities have been proposed as to the mechanism by which the mutation causes preferential injury to the basal ganglia. The present chapter provides a basic overview of the genetics and pathology of HD.

Sequencing the unsequenceable: Expanded CGG-repeat alleles of the fragile X gene

“…These results demonstrate that FMR1 alleles can be readily sequenced through the threshold region separating premutation and full mutation alleles (;200 CGG repeats), and well into the full mutation region that gives rise to FXS through methylation-coupled gene silencing. More broadly, the current work serves as a proof of concept for the study of additional repeat expansions that are associated with other diseases, such as myotonic dystrophy (Lee and Cooper 2009;Sicot et al 2011), Huntington's disease (Reiner et al 2011), Friedreich's ataxia (Koeppen 2011), and the recently discovered hexanucleotide (GGGGCC) repeat disorder ALS-FTLD (Braida et al 2010;Hannan 2010;DeJesusHernandez et al 2011).…”

Structure, function, and regulation of mitofusin‐2 in health and disease

“…Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder causing progressive cognitive and behavioural symptoms as a result of an expansion of CAG repeats within the huntingtin (Htt) gene (Reiner, Dragatsis & Dietrich, 2011). Aberrations in mitochondrial dynamics have been linked to neurodegeneration in HD (Bossy-Wetzel, Petrilli & Knott, 2008).…”

Drug or disease - Differentiating and managing motor symptoms associated with late onset Huntington’s disease from extrapyramidal side-effects of antipsychotics

“…The condition affects both sexes equally with a mean age of onset of about 40 years. The age of onset ranges between 4 years to 80 years in the present literature [2].…”

“…The genetic basis for Huntington's disease is a mutation resulting CAG repeat expansion to >35 CAG sequence repeats in the gene which codes for a protein known as huntingtin present on the short arm of chromosome 4 [2]. In the general population, CAG sequence repeats range from 9-11 to 34-37 with an average of 17-20 [4].…”

“…It affects the basal ganglia initially and leads to cognitive, affective, motor and behavioural decline with the passage of time [2].…”