DRPLA - Dentatorubral-Pallidoluysian Atrophy

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Gene Symbol: ATN1

Chromosomal Locus: 12p13.31
Protein: Atrophin 1
Pseudonyms: Haw River Syndrome, HRS, Ataxia, Chorea, Seizures, Dementia
Precise characterization of the expanded CAG trinucleotide repeat of the ATN1 gene by polymerase chain reaction (PCR) and fluorescent capillary electrophoresis utilizing an internal standard and allelic ladder.
  • Collect: Prefer two 5ml whole blood EDTA (lavender top) tube.
  • Min. Collection: 0.7 ml whole blood EDTA.
  • Transport: blood EDTA at Room Temp shipped regular next day air (No Saturday delivery; store specimen at 4°C and ship Monday).
  • Stability: Ambient: up to 7 days; Refrigerated: 2 weeks. Frozen: unacceptable
  • Unacceptable Conditions: Serum. Frozen or severely hemolyzed blood. Clotted blood.
  • Prenatal testing: Direct: 5ml direct unspun amniotic fluid or 15mg CVS tissue with a backup flask growing. Culture: confluent T25 flask. Maternal blood sample is required for maternal cell contamination studies.
A Molecular Genetics Laboratory Test Requisition must accompany the specimen. Contact the Molecular Laboratory at 918-502-1721 to obtain further information.
Counseling and informed consent are recommended for genetic testing and are told for predictive testing. The Center for Genetic Testing at Saint Francis Consent Form is available.
DRPLA is an adult onset dominant disorder and therefore the Huntington Disease testing protocol is followed as the standard of care for predictive testing.
  1. For symptomatic individuals, testing is ordered by the patient caregiver.
  2. For minors, predictive testing is discouraged and testing should only be pursued for diagnostic reasons.
  3. For predictive testing, a patient requests enrollment in a Presymptomatic Program involving education, genetic counseling, waiting periods, special informed consent and involvement of psychological support.
Note: For predictive testing, it is important to first document the presence of a CAG-repeat amplification in the ATN1 gene in an affected family member to confirm that the molecular expansion is the underlying mechanism of disease in the family.
Incidence: Rare
Inheritance: Autosomal dominant. Variable age of onset but complete penetrance.
Disease Characteristics:
Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder that is characterized by progressive myoclonus, epilepsy, ataxia choreoathetosis and dementia. DRPLA can closely resemble the symptoms of Huntington disease and is often a reflexive test if the patient is not found to have Huntington disease.
The disease onset is between 20 and 70 years of age.
Molecular Genetic Mechanism: DRPLA is a neurodegenerative disorder that demonstrates the genetic anticipation characteristic of an unstable expansion of CAG trinucleotide repeats within the coding region of the ATN1 gene. This glutamine repeat region is found to be polymorphic in the normal population with sizes ranging from 6 to 35 repeats. Expansions between 36 and 47 repeats are mutable intermediate alleles with uncertain penetrance. Expansions of 48 and above are considered to be fully penetrant and diagnostic for the disease.
Reference Ranges:
Normal alleles: 6 to 35 CAG repeats
Mutable Alleles (Uncertain/Reduced Penetrance): 36 to 47 CAG repeats
Abnormal Alleles: > 48 CAG repeats
Clinical Sensitivity: 99%
Analytical Sensitivity: 99%
Test Limitations: This test examines the CAG repeat expansion region exclusively. Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.
  • Individuals with a family history of DRPLA who want to determine their true risk.
  • Families considering future medical and disability insurance needs.
  • Individuals at risk who wish prenatal diagnosis.
  • To determine whether individuals with an ataxia have HD or DRPLA.