Huntington Disease (HD), OMIM #143100

Background and Standard Service Information

Huntington disease (HD) is an autosomal dominant progressive neurodegenerative disease, caused by mutation in the HTT gene on chromosome 4p. Typical clinical features include motor symptoms, cognitive deterioration, and psychiatric symptoms.

The nature of the mutation is an increase in the number of CAG repeats within exon 1 of this gene. Patients with HD have an allele with 36 or more repeats. Alleles are classified according to CAG repeat number as follows:

Am J Hum Genet 62, 1243-7, 1998
CAG repeat no. Allele description
≤ 26 Normal allele
27 – 35 Mutable normal allele – may occasionally mutate to HD alleles in subsequent generations
36 – 39 HD allele with reduced penetrance
≥ 40 HD allele

Laboratory tests determine the number of CAG repeats in patient samples.

Essential referral information

In addition to supplying standard patient identification and referral information, the following should be clearly indicated:

Samples required

Generally 5-10ml of EDTA blood (FBC bottle) is required. Blood specimens must be appropriately packaged, and preferably sent by courier to arrive as soon as possible. Do not freeze prior or during postage. Please note that extracted DNA is stored from patient’s samples at the National Centre for Medical Genetics, and kept indefinitely unless a written request for its disposal is received from the patient or their parent/guardian.

Restrictions on Testing

Tests offered

A number of tests are performed on a routine basis. Molecular confirmation of Huntington Disease (HD) is possible using a PCR based assay to detect the number of CAG repeats within exon 1 of the HTT gene. See the table above for the classification of these alleles.

  1. Diagnostic tests for patients with clinical symptoms suggestive of Huntington disease (HD). Due to the implications of a positive test result, we recommend that such tests should be performed only with full informed consent of the patient.
  2. Predictive tests for asymptomatic individuals who have a family history of HD. Such tests are only performed in conjunction with a counselling programme run by the National Centre for Medical Genetics. Patients should be referred to the Director, Prof. A. Green.
  3. Prenatal testing must be arranged in advance with the laboratory through our own Clinical Genetics team.

Diagnostic sensitivity of tests

The test is highly sensitive and highly specific. An HD allele is detected in ~100% of affected individuals; HD alleles are detected in ~0% of normal individuals; individuals with a family history of HD and who have an HD allele are ~100% likely to develop the disease within the average lifespan.


Following laboratory analysis, a report is prepared which gives results based on the CAG repeat classification system above. This is sent to the referring clinician. Results are given in the form of a written interpretative report to the referring clinician.

Target reporting times

As reporting times are constantly evolving, please refer to the molecular genetics homepage, or contact the molecular genetics laboratory, to receive up-to-date information on anticipated reporting times for your referral.

The following are current target reporting times for each category of test offered (information correct as of 12/01/10):

Routine Query Affected 8-10 wks
Predictive 4 wks after 2nd sample has been received.
Prenatal diagnosis 2 wks (CVS) 4 wks (amnio)

Further tests

Please contact the laboratory to arrange any other related tests, eg prenatal diagnosis, prenatal exclusion testing, or testing for Dentatorubral-Pallidoluysian atrophy (DRPLA) or Spinal Cerebellar Ataxia (SCA) – which may be advised for a query affected patient who has been shown to not have Huntington Disease.

The NCMG Molecular Genetics laboratory participates in external QA schemes run by the UK NEQAS for Molecular Genetics, the European Molecular Genetics Quality Network (EMQN), and the Cystic Fibrosis European Network. Results of assessments are available for inspection upon request.

Document Number: DOC509, Revision Number 5