Table 7.

Methods to Characterize ATXN8OS/ATXN8 (CTA·TAG)n(CTG·CAG)n Repeats

Interpretation of
(CTA·TAG)n(CTG·CAG)n 1
Repeat Number		Expected Results by Method
Conventional
PCR		Repeat-primed PCR 2Expanded repeat
analysis 3, 4
Normal: 15-50Detected 5See footnote 2.Expansions can be
detected & repeat
size can be
approximated. 6, 7
Intermediate 8Expansion may be
detected depending
on allele size. 4, 5		Expansions may be
detected but repeat size
cannot be determined. 9, 10
Pathogenic: 71-~1300Not detectedExpansions detected,
but repeat size cannot
be determined. 9
1.

CTG·CAG and CTA·TAG refer to the forward and reverse sequences of two adjacent three base-pair repeat sequences.

2.

The design of an RP-PCR assay may include conventional PCR primers to size normal repeats and detect expanded repeats in a single assay. The RP-PCR assay itself does not determine repeat size, even alleles in the normal range.

3.

Methods of expanded repeat analysis to detect and approximate the size of expanded repeats include long-range PCR sized by gel electrophoresis and Southern blotting.

4.

The upper limit of repeat size detected will vary by assay design, laboratory, sample, and/or patient as a result of competition by the normal allele during amplification.

5.

Detection of an apparently homozygous normal allele does not rule out the presence of an expanded (CTA·TAG)n(CTG·CAG)n repeat; thus, testing by RP-PCR or expanded repeat analysis is required to detect a repeat expansion.

6.

Southern blotting for the CAG repeat expansion has been described [Koob et al 1999].

7.

Precise sizing of repeats is not necessary as clinical utility for determining the exact repeat number has not been demonstrated.

8.

The clinical significance of SCA8 alleles in the 51-70 repeat range is currently unclear but repeats in this range appear to be less likely to result in disease.

9.

RP-PCR (referred to as triplet-primed PCR; TP-PCR) for the CAG repeat expansion has been described [Tanaka et al 2011].

10.

Repeats at the lower end of this range may not show the characteristic stutter pattern that indicates an expanded repeat.

From: Spinocerebellar Ataxia Type 8

Cover of GeneReviews®
GeneReviews® [Internet].
Adam MP, Feldman J, Mirzaa GM, et al., editors.
Seattle (WA): University of Washington, Seattle; 1993-2024.
Copyright © 1993-2024, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.