Targeted exome analysis identifies the genetic basis of disease in over 50% of patients with a wide range of ataxia-related phenotypes

Miao Sun, Amy Knight Johnson, Viswateja Nelakuditi, Lucia Guidugli, David Fischer, Kelly Arndt, Lan Ma, Erin Sandford, Vikram Shakkottai, Kym Boycott, Jodi Warman Chardon, Zejuan Li, Daniela del Gaudio, Margit Burmeister, Christopher M. Gomez, Darrel J. Waggoner, Soma Das

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Purpose: To examine the impact of a targeted exome approach for the molecular diagnosis of patients nationwide with a wide range of ataxia-related phenotypes. Methods: One hundred and seventy patients with ataxia of unknown etiology referred from clinics throughout the United States and Canada were studied using a targeted exome approach. Patients ranged in age from 2 to 88 years. Analysis was focused on 441 curated genes associated with ataxia and ataxia-like conditions. Results: Pathogenic and suspected diagnostic variants were identified in 88 of the 170 patients, providing a positive molecular diagnostic rate of 52%. Forty-six different genes were implicated, with the six most commonly mutated genes being SPG7, SYNE1, ADCK3, CACNA1A, ATP1A3, and SPTBN2, which accounted for >40% of the positive cases. In many cases a diagnosis was provided for conditions that were not suspected and resulted in the broadening of the clinical spectrum of several conditions. Conclusion: Exome sequencing with targeted analysis provides a high-yield approach for the genetic diagnosis of ataxia-related conditions. This is the largest targeted exome study performed to date in patients with ataxia and ataxia-like conditions and represents patients with a wide range of ataxia phenotypes typically encountered in neurology and genetics clinics.

Original languageEnglish (US)
Pages (from-to)195-206
Number of pages12
JournalGenetics in Medicine
Issue number1
StatePublished - Jan 1 2019
Externally publishedYes


  • ataxia
  • clinical
  • diagnosis
  • exome sequencing
  • molecular genetics

ASJC Scopus subject areas

  • Genetics(clinical)


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