Huntington's Disease (HD) is an autosomal dominant, progressive neurodegenerative disorder characterized by
motor disturbance, cognitive loss, and psychiatric manifestations, which usually manifests at around 40 to 50 years
of age. It has an incidence of about 1 in 10,000 individuals of European descent. In 5 - 10% of cases, HD is
expressed in juveniles, typically presenting with more severe symptoms and a more rapid course. HTT is the gene
implicated in HD and contains a normally polymorphic trinucleotide CAG repeat region in the first exon. Normal
individuals have between 6 and 35 copies of this repeat. Affected individuals have an expanded repeat region,
usually 36 to 121 copies of the repeat. The penetrance of the CAG expansion is not complete, therefore showing
variability in the severity of disease symptoms. Individuals with a CAG repeat size of 30 to 35 do not manifest
Huntington's Disease themselves, however, the risk that their offspring will develop HD may be increased,
particularly from paternal transmission of the gene.
Detection of CAG expansions in the HTT gene that lead to Huntington's Disease. The test is done on peripheral blood
specimens for confirmation of clinical diagnosis, carrier status or presymptomatic testing.
Determination of an expanded trinucleotide CAG repeat region is based on PCR amplification of the Huntingtin
(HTT) gene using a pair of primers specific for the surrounding region. The product size is determined using a size
standard, and CAG repeat number is calculated.
HTT exon 1 variable region
Peripheral blood collected in EDTA (purple top) is preferred, 3-10mL.
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