Huntington disease: Genetics and pathogenesis
- Huda Y Zoghbi, MD
Huda Y Zoghbi, MD
- Professor, Departments of Pediatrics, Neurology, Neuroscience, and Molecular and Human Genetics
- Baylor College of Medicine
- Harry T Orr, PhD
Harry T Orr, PhD
- University of Minnesota
- Institute for Translational Neuroscience
- Section Editors
- Marc C Patterson, MD, FRACP
Marc C Patterson, MD, FRACP
- Section Editor — Pediatric Neurology
- Professor of Neurology, Pediatrics, and Medical Genetics
- Chair, Division of Child and Adolescent Neurology
- Mayo Clinic College of Medicine
- Helen V Firth, DM, FRCP, DCH
Helen V Firth, DM, FRCP, DCH
- Section Editor — Genetics
- Consultant Clinical Geneticist
- Addenbrooke's Hospital, Cambridge, UK
Unstable trinucleotide repeats are associated with a variety of neurodegenerative diseases. Nine of these disorders are associated with expansion of cytosine-adenine-guanine (CAG) repeats that encode for polyglutamine tracts in the protein products. Included in this group are Huntington disease (HD), spinobulbar muscular atrophy, dentatorubral pallidoluysian atrophy, and some of the spinocerebellar ataxias.
The most common presenting symptom of HD in adults is chorea (hence the name Huntington chorea). Other usual findings at presentation include memory deficits, affective disturbances, personality changes, and other manifestations of motor dysfunction such as parkinsonism and dystonia. Patients with juvenile-onset HD have minimal or no chorea, but develop myoclonus and seizures as well as cognitive and behavioral problems. Children also have a more rapidly progressive disease.
The genetics and pathogenesis of HD will be reviewed here. Clinical aspects and management of HD are discussed separately. (See "Huntington disease: Clinical features and diagnosis" and "Huntington disease: Management".)
Huntington disease (HD) is caused by expansion of the cytosine-adenine-guanine (CAG) trinucleotide repeats in the HTT gene (also known as the HD or IT15 gene) located on chromosome 4p16.3 that encodes the protein huntingtin [1-3]. Mutant huntingtin contains an expanded tract of glutamine residues, which is located near its amino terminal. The disease is transmitted in an autosomal dominant manner.
HD shares several clinical features with the other polyglutamine diseases:To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
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