Last update: 05/06/2006

Background to disease

OMIM 143100

Huntington disease (HD) is an autosomal dominant neurodegenerative disorder. Manifestations include choreic movements, cognitive decline, and psychiatric disturbances. Typically, onset is in late adulthood with progressive worsening. Juvenile-onset HD is rare, but more severe and presents with characteristic rigidity.

HD is caused by expansions of a CAG repeat within the coding region of the HD gene. The expanded repeat translates into an abnormally large polyglutamine tract, which is toxic, resulting in neuronal death in particular brain regions. There is an inverse correlation between repeat number and age of onset; on average, the larger the expansion the earlier the symptoms appear.

Allele classes (CAG repeats):

Normal = 5 – 28.

Normal mutable = 29 – 35. Not pathogenic but may expand on paternal transmission.

Partially penetrant = 36 – 39. Potentially pathogenic.

Pathogenic = >39. Invariably disease-causing.

Laboratory Analysis

Contact scientist: Lampros Mavrogiannis

	Test	Target reporting time (working days)
1.	CAG repeat sizing PCR	10
2.	CAG + CCG compound repeat sizing PCR	10
3.	Analysis of 4 linked markers	20