Note: Effective June 22, 2026, our laboratory has implemented long-read sequencing for repeat expansion panel testing, complementing our existing PCR/repeat-primed PCR–based approach.
Long-read sequencing provides more accurate repeat sizing and enables improved characterization of complex repeat expansions, enhancing the quality and detail of test results. Because this methodology requires high-quality, high-molecular-weight DNA, buccal swab specimens will no longer be accepted for repeat expansion panel testing. Blood and saliva specimens remain acceptable and are well suited for long-read sequencing analysis. Our laboratory will provide saliva collection kits for patients requiring repeat expansion testing if requested by the ordering provider.
Ataxias, hereditary or sporadic, represent a clinically and genetically complex group of neurological disorders that are characterized by uncoordinated body movements and may present with gait abnormalities, dysarthria, apraxia, dysphagia and other pyramidal and extrapyramidal signs. The ataxia symptom can be isolated or part of a multisystemic neurological disorder, presenting at ages ranging from infancy to adulthood, and can be dominant, recessive, X-linked or mitochondrial. Genetic testing for hereditary ataxias remains challenging mostly due to the significant clinical overlap and genetic heterogeneity with more than 500 genes reported to be associated with ataxia or ataxia-like presentation. Targeted exome sequencing is regarded as a powerful diagnostic tool for heterogeneous neurological disorders such as ataxia but limited in its ability to detect repeat expansions which are estimated to account for over 50% of dominant hereditary ataxias. The ataxia exome involves analysis of exome sequencing data in a predefined set of genes associated with ataxia and ataxia-related disorders. The most common repeat expansion disorders include the autosomal dominant spinocerebellar ataxias (SCAs) and the autosomal recessive Friedreich ataxia. Fragile X-associated tremor/ataxia syndrome (FXTAS), caused by a premutation in the FMR1 gene, is the most common X-linked cause of cerebellar ataxia. Recently, a biallelic intronic expansion in the RFC1 gene has recently been identified in the majority of patients with CANVAS (Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome) and in a proportion of late onset ataxia patients. An intronic GAA expansion in the FGF14 gene has recently been identified in several individuals with previously unexplained late-onset ataxia (PMID: 36516086, 36493768). The identification of this intronic expansion has led to the discovery of a new form of autosomal dominant hereditary ataxia, spinocerebellar ataxia type 27B (SCA27B). The concurrent testing option includes simultaneous repeat expansion and exome sequence analysis.
