Gene Symbol: CACNA1A
Chromosomal Locus: 19p13.2
Protein: calcium channel, L type, alpha-1 polypeptide
Spinocerebellar ataxia type 6, FHM, MHP,episodic ataxis type 2
TURNAROUND TIME: 10 days
Polymerase chain reaction (PCR) that brackets the CACNA1A gene 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: less than 1 in 100,000.
Inheritance: Autosomal dominant. Variable age of onset but complete penetrance.
Initial symptoms are gait unsteadiness, stumbling, and imbalance and/or dysarthria. Symptoms progress slowly, and eventually all persons have gait ataxia, upper-limb incoordination, intention tremor, and dysarthria. In contrast to the other SCAs and HD, individuals with SCA6 ataxia could be expected to have a normal life span with progressive and debilitating symptoms.
Molecular Genetic Mechanism: Normal and clinically unaffected individuals 18 or less CAG repeats (the amino acid glutamine) in the coding region of the gene. An allele repeat of 19 CAG repeats has an unclear clinical significance. Expansions of 20 to 33 repeats are fully penetrant for disease.
Reference Ranges (CAG repeats):
Normal alleles: < 18
Unclassified Allele : 19
Abnormal Alleles : 20 to 33
Clinical Sensitivity: 99%
Test Limitations: This test examines the CAG repeat regions, exclusively. However, no other mechanism has been described for SCA6 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.
INDICATIONS FOR USE:
- Individuals with a family history of SCA6 who want to determine their risk.
- Families considering future medical and disability insurance needs.
- To determine whether individuals with an ataxia SCA6
- To differentiate individuals with SCA6 from other ataxias.