Early Onset Torsion Dystonia 1 (DYT1, OMIM #128100)

Background and Standard Service Information

Early onset torsion dystonia is an autosomal dominant disorder due to a deletion mutation in the TOR1A gene on chromosome 9q34.

Penetrance is low: around 30% of individuals with a mutation express the disease. However penetrance varies between families. A 3-bp GAG deletion (c.904_906delGAG) in the Exon 5 region of the TOR1A gene is the only mutation so far detected in a large number of patients from different ethnic backgrounds. DYT1 represents only one of a clinically and genetically heterogeneous group of idiopathic torsion dystonias. Most patients with atypical presentation for DYT1 do not have the GAG deletion.

Primary torsion dystonia usually begins in childhood or adolescence with involuntary posturing of the trunk, neck, or limbs. Early-onset primary dystonia (DYT1) is considered a primary dystonia because it is not associated with other neurologic abnormalities.

Essential referral information

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

  1. Patient’s symptoms.
  2. Any family history, including names, dates of birth, relationship and genetic test results if available.

It is the responsibility of the referring clinician to ensure consent has been obtained for testing and storage.

Samples required

3-5ml of blood in an EDTA tube. 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

Testing would not normally be considered for asymptomatic children under the age of 16. This policy is consistent with international guidelines for genetic testing of children.

Tests offered

Standard analysis is to test for a 3-bp GAG deletion (c.904_906delGAG) in the Exon 5 region of the TOR1A gene. Testing performed includes the following:

Prenatal testing must be arranged in advance with the laboratory, through a Clinical Genetics department if possible.

Analysis methodology based on Ozelius et al. 1997, Nature Genet. 17, 40-8

Diagnostic sensitivity of tests

Diagnostic testing of DYT1 is carried out to reveal the presence or absence of a 3 bp deletion, c.904_906delGAG, in affected individuals. Other forms of torsion dystonia are not excluded by this analysis.

Please contact the laboratory if it is appropriate to perform other tests.

Interpretation

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 11/01/2010): Target reporting time for DYT1 is up to 6 months. Analysis is performed in batches due to low supply of positive control.

Further tests

Please contact the laboratory to discuss any other tests, e.g. possible linkage studies for large families with no 3bp GAG deletion in DYT1.

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: DOC460, Revision Number 3