Gene Symbol: ATXN2
Chromosomal Locus: 12q24.12
Protein: ataxin 2
Pseudonyms: Spinocerebellar ataxia type 2, Olivopontocerebellar ataxia, type 2
TURNAROUND TIME: 10 days
Polymerase chain reaction (PCR) that brackets the ATXN2 CAG repeat region using fluorescent capillary electrophoresis for fragment size analysis.
- 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 refrigerated 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.
Counseling and informed consent are recommended for genetic testing. A consent form
is available as a resource.
Incidence: Unknown. 13-18% of autosomal dominant ataxias.
Inheritance: Autosomal dominant. Variable age of onset but complete penetrance.
Disease Characteristics: Disease onset ranges from infancy to adulthood. Slow progressive cerebellar ataxia and saccadic eye movements, as well as a relatively high incidence of dystonia or chorea and dementia. Once the involuntary neurological symptoms start affecting autonomic muscle systems death occurs rapidly. The size of the CAG repeat region dictates the age of onset and the speed of the progression of symptoms rather than the actual spectrum of symptoms. Age of onset can be as early as infancy.
Molecular Genetic Mechanism: Normaland clinically unaffected individuals have between 13 and 31 CAG repeats (the amino acid glutamine) in the coding region of the gene. Expansions of 32 repeats and more will be fully penetrant for disease. The age of onset and increase of CAG size often increases in each generation (Anticipation).
Reference Ranges (CAG repeats):
Normal alleles: 13 to 31
Abnormal Alleles: > 32 (over 100 repeats exceeds the detectable range for PCR and would require Southern blot analysis)
Clinical Sensitivity: 99%
Analytical Sensitivity: 99%
Test Limitations: This test examines the CAG repeat regions, exclusively. However, no other mechanism has been described for SCA2 and the test is considered diagnostic. 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. Rare diagnostic errors can occur due to primer or probe site mutations or rare polymorphisms. Expansions with over 100 repeats fall outside of the detectable range by PCR and would require Southern Blot analysis.
INDICATIONS FOR USE:
- Individuals with a family history of SCA2 who want to determine their risk.
- Families considering future medical and disability insurance needs.
- To determine whether individuals with an ataxia and slow eye movements have SCA2
- To differentiate individuals with SCA2 from other ataxias.