Gene Symbol: ATXN7
Chromosomal Locus: 3p14.1
Pseudonyms: Spinocerebellar ataxia type 7, Olivopontocerebellar Atrophy III;
OPCA3TURNAROUND TIME: 10 days
Polymerase chain reaction (PCR) that brackets the ATXN7 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.Estimated at 2% of all ataxias.
Inheritance: Autosomal dominant. Variable age of onset but complete penetrance.
Disease onset ranges from infancy to adulthood. Early death occurs in the fifth or occasionally sixth decade with slowly progressive retinal degeneration and cerebellar ataxia. Retinal degeneration in adults is characterized by abnormalities in color vision and central visual acuity, often presenting before the onset of cerebellar findings. 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 less than 19 CAG repeats (the amino acid glutamine) in the coding region of the gene. Mutable alleles with no clinical manifestations are associated with 28-33 repeats. 34-36 repeats result in incomplete penetrance. An expansion of 36 or higher repeats the disease will be full penetrant. The age of onset and increase of CAG size often increases each generation, especially during father to child transmission (Anticipation).
Reference Ranges (CAG Repeats):
Normal alleles: 4 to 19
Mutable Normal Alleles: 28 to 33
Reduced Penetrance Abnormal Alleles: 34 to 35
Abnormal Alleles: > 36 (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 SCA7 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 SCA7 who want to determine their risk.
- Families considering future medical and disability insurance needs.
- Individuals at risk who wish prenatal diagnosis.
- To determine whether individuals with an ataxia and central vision loss and blindness may have SCA7.
- To differentiate individuals with SCA7 from other ataxias.