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HelpTest Code DRPL Dentatorubral-Pallidoluysian Atrophy (DRPLA) Gene Analysis, Varies
Reporting Name
DRPLA Gene AnalysisUseful For
Confirming the diagnosis of dentatorubral-pallidoluysian atrophy (DRPLA) for symptomatic patients
Predictive testing for individuals with a family history of DRPLA and a documented expansion in the ATN1 gene in an affected family member
Method Name
Polymerase Chain Reaction (PCR)
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Specimen Type
VariesShipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Specimen Required
Specimen Type: Whole blood
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Ambient (preferred) | ||
| Frozen | |||
| Refrigerated | |||
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.Special Instructions
Reference Values
Normal alleles: 7-35 CAG repeats
Abnormal alleles: 49-93 CAG repeats
An interpretive report will be provided.
Day(s) Performed
Tuesday
CPT Code Information
81177-ATN1 (ataxin 2) (eg, denatatorubral-pallidolyuysian atrophy) gene analysis, evaluation to detect abnormal (eg, expanded) alleles
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| DRPL | DRPLA Gene Analysis | In Process |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 53234 | Result Summary | 50397-9 |
| 53235 | Result | 49631-5 |
| 53236 | Interpretation | 69047-9 |
| 53237 | Specimen | 31208-2 |
| 53238 | Source | 31208-2 |
| 53239 | Released By | 18771-6 |
Clinical Information
Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder characterized by ataxia, choreoathetosis, dementia, and psychiatric disturbance in adults and ataxia, myoclonus, seizures, and progressive intellectual deterioration in children. Characteristic neuropathologic observations include degeneration of the dentatorubral and pallidoluysian systems of the central nervous system.
The prevalence of DRPLA depends on the geographic and ethnic origin of the population being studied. DRPLA was first described in a European individual without a family history; however, it is predominantly found as an inherited condition and is most prevalent in Japan (0.2-0.7 per 100,000). Although rare, DRPLA has been identified in other populations, including Europe and North America.
DRPLA is caused by an expansion of the CAG trinucleotide repeat in the ATN1 (DRPLA) gene. This trinucleotide repeat is polymorphic in the general population, with the number of repeats ranging from 7 to 35. In affected individuals, the CAG expansion ranges from 48 to 93 repeats. As with other trinucleotide repeat disorders, anticipation is frequently observed, and larger CAG expansions are associated with earlier onset and a more severe and rapid clinical course. In DRPLA, the observed anticipation appears to be significantly greater in paternal transmissions.
Interpretation
An interpretive report will be provided.
Cautions
For predictive testing, it is important to first document the presence of CAG-repeat amplification in the ATN1 gene in an affected family member to confirm that molecular expansion is the underlying mechanism of disease in the family.
It is strongly recommended that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.
Predictive testing of an asymptomatic child is not recommended.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in the interpretation of results may occur if information given is inaccurate or incomplete.
The absence of an expansion in the ATN1 gene does not eliminate the diagnosis of other inherited neurodegenerative disorders that have overlapping clinical features with DRPLA, such as Huntington disease or spinocerebellar ataxias.
Supportive Data
Method validation involved comparative studies with other laboratories and testing 50 individuals from the general population (anonymous blood donors) and 48 patients with cerebellar ataxia. In each case, the distribution of observed repeat sizes closely correlated with previously reported values (ie, similar range and frequencies of specific repeat sizes). Sequencing of 2 specimens confirmed accuracy of CAG repeat numbers compared with estimations based on the size of polymerase chain reaction products.
Clinical Reference
1. Ikeuchi T, Onodera O, Oyake M, Koide R, Tanaka H, Tsuji S: Dentatorubral-pallidoluysian atrophy (DRPLA): close correlation of CAG repeat expansions with the wide spectrum of clinical presentations and prominent anticipation. Semin Cell Biol. 1995 Feb;6(1):37-44
2. Tsuji S: Dentatorubral-pallidoluysian atrophy: clinical aspects and molecular genetics. Ad Neurol. 2002;89:231-239
3. Oyanagi S: Hereditary dentatorubral-pallidoluysian atrophy. Neuropathology. 2000 Sep;20 Suppl:S42-S46
Method Description
A polymerase chain reaction-based assay is used to amplify across the region of the ATN1 (DRPLA) gene containing the CAG repeats. Assay products are separated by capillary electrophoresis and are sized by comparison with an internal size standard.(Dorschner MO, Barden D, Stephens K: Diagnosis of five spinocerebellar ataxia disorders by multiplex amplification and capillary electrophoresis. J Mol Diag. 2002 May;4(2):108-113)
Report Available
14 to 21 daysTest Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.Forms
1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing (Spanish) (T826)
2. Molecular Genetics: Neurology Patient Information
3. If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.