Spinocerebellar Ataxia 3 (SCA3)

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Gene Symbol:  ATXN3 
Chromosomal Locus: 14q32.12  
Protein:  ataxin 3 
Pseudonyms: Machado-Joseph disease,Spinocerebellar ataxia type 3, Olivopontocerebellar ataxia, type 3
TURNAROUND TIME:     10 days
Polymerase chain reaction (PCR) that brackets the ATXN3 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.
A Molecular Genetics Laboratory Test Requisition must accompany the specimen. Contact the Molecular Laboratory at 918-502-1721 to obtain further information.
Note: Counseling and informed consent are recommended for genetic testing. A consent form is available as a resource.
Incidence: Unknown.  23% of autosomal dominant ataxias. There is an especially high incidence in populations from the Azores.
Inheritance: Autosomal dominant. Variable age of onset but complete penetrance.
Disease Characteristics:
Slowly progressive cerebellar ataxia, gait problems, speech difficulties, clumsiness, and often visual blurring and diplopia. Saccadic eye movements become slow and ophthalmoparesis develops, resulting initially in up-gaze restriction. Later, severe ataxia of limbs and gait associated with muscle wasting is observed. 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.
Molecular Genetic Mechanism: Normal and clinically unaffected individuals have between 11 and 44 CAG repeats (the amino acid glutamine) in the coding region of the gene. Expansions of 45 to 51 repeats result in incomplete penetrance. Expansions of 52 repeats or higher 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:  11 to 44
Abnormal with Reduced Penetrance Alleles: 45 to 51
Abnormal Alleles: over 52
Related Tests: SCA Panel, HD, DRPLAFRDA and Neurological Panel  
Clinical Sensitivity: 99%
Analytical Sensitivity:99%
Test Limitations:  This test examines the CAG repeat regions, exclusively. However, no other mechanism has been described for SCA3 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.
  • Individuals with a family history of SCA3 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 SCA3
  • To differentiate individuals with SCA3 from other ataxias.