Diagnosis of Spinocerebellar Ataxias Caused by Trinucleotide Repeat Expansions

Abstract

Spinocerebellar ataxias (SCAs) are a group of disorders that are both clinically and genetically heterogeneous. They usually demonstrate onset in adulthood, but some forms may have juvenile or infantile onset. There are many different types of SCA, demonstrating different modes of inheritance and types of mutation. The most common forms are due to dominantly inherited expansions in trinucleotide repeat sequences located within the coding region of the relevant genes, and these are readily identifiable by molecular genetic testing. In general, it is possible to test for these disorders using PCR-based assays, amplifying across the trinucleotide repeat regions and sizing the PCR products to determine the number of repeats. Larger expansions are generally associated with a more severe presentation of the disorder, and alternative methods may be necessary to detect these alleles. This protocol describes methods for detecting normal and expanded triplet repeat alleles in the most common SCA genes. © 2017 by John Wiley & Sons, Inc.