Introduction
The most common hereditary ataxias (HAs) are the spinocerebellar ataxias (SCAs) with nucleotide repeat expansions as the primary molecular mechanism. Repeat expansion testing, which cannot be readily evaluated with current short-read next-generation sequencing (NGS) technologies, is typically performed first. If uninformative, an NGS-based multigene panel or exome sequencing may be pursued. While the yield from NGS-based testing has been reported, cohorts were small, and few studies included mitochondrial DNA (mtDNA) analysis. To inform the clinical utility of NGS panel testing, including mtDNA analysis, we describe the genetic findings of this testing approach for a cohort of patients with suspected HA.
Genetic testing adds value for individuals with ataxia and presumed uninformative repeat expansion testing
- 1 in every 7 individuals tested received a positive result
A positive genetic test result can impact medical management for individuals with ataxia
- 1 in every 4 individuals with a positive result had a variant in a gene associated with an interventional clinical trial or gene-specific therapy
Assessment of the mitochondrial genome is important for individuals with ataxia
- 1 in every 25 individuals with ataxia had a positive result in a mitochondrial gene
Authors:
Kimberly Gall, Julie Hathaway, Allison Sluyters, Lotta Koskinen, Eija Seppälä, Kirsi Alakurtti, Monica Segura Castell, Åsa Hagström, Rocio Sanchez Alcudia, Heli Kuisma, Inka Saarinen, Mikko Muona, Tuuli Pietilä, Matias Rantanen, Massimiliano Gentile, Pertteli Salmenperä, Jussi Paananen, Samuel Myllykangas, Juha Koskenvuo.
Presented at CAGC 2023