Torsion Dystonia: TOR1A Targeted Sequencing

Diagnostic Use

TOR1A sequencing may be used to confirm a diagnosis of early-onset torsion dystonia (DYT1). Early-onset torsion dystonia represents the commonest and most severe form of hereditary dystonia. It is an autosomal dominantly inherited movement disorder characterised by twisting muscle contractures that usually begins in childhood. Almost all cases are due to a deletion of nucleotides 904 to 906 of the TOR1A gene on chromosome 9q34 resulting in the loss of one of a pair of glutamic acid residues in a conserved region of the ATP-binding protein torsinA. Penetrance is estimated at 30% (70% of individuals who inherit the mutation do not develop DYT1).

Department

Genetics - Molecular Pathology

Delphic Registration Code

MOLP

Constituent Tests

• Genomic DNA Extraction

Synonyms

DYT1
Early-onset torsion dystonia
hereditary dystonia
Primary dystonia

Turnaround Time

4 weeks

Test Code

4587

Specimen Type

• Whole Blood

Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

4.0

No of Samples Required

1

Paediatric Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

1.0

Minimum Sample Volume (ml)

0.5

Pre-testing Requirements

Most individuals with DYT1 will have an affected parent, and sibs at 50% risk. It is appropriate to offer genetic counselling to individuals and families seeking a diagnosis of DYT1 in order to help them make informed decisions about testing. Genetic counselling is available in NZ from Northern Regional Genetics Services (Ph 0800-476-123) or Central and Southern Regional Genetic Services (Ph 0508-364-436).

Additional Specimen Information

This genetic test needs nucleated cells. Please don’t centrifuge or freeze the EDTA blood tube.
If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Aliquot Instructions

Sample Type

• Whole Blood

Transport to Lab

Ambient (8 - 24 degrees Celsius)

Additional Referral/Aliquot Information

Please don’t centrifuge or freeze the EDTA blood tube.
If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Interpretation

Detection of the TOR1A:c.904_906delGAG establishes a diagnosis of DYT1 in symptomatic individuals.

Reference Intervals

Test Method

Exon 5 of the TOR1A gene is analysed by bidirectional automated DNA sequencing.

Non-Funded Test Cost

$213.17 (Exclusive of GST)

Billing Code

4587

Uncertainty of Measurement:
Automated bidirectional DNA sequencing has an analytical sensitivity and specificity of >99%. Note that the lower limit of variant detection of sequencing analysis is ~10%, this is important to consider in the case of mosaicism, mitochondrial, and somatic variation that is not expected to be present at 50% or 100%. This analysis will not detect variants located within intronic regions, except at the intron-exon boundaries.

Genomic DNA must be extracted from the specimen prior to testing. This incurs an additional charge (see GDNA). Laboratories may prefer to submit DNA for testing. Please provide a minimum of 5 micrograms of DNA at 20 nanograms / microlitre.

Contact Information

Enquiry Form