Scientific Publications Database

Article Title: Targeted exome analysis identifies the genetic basis of disease in over 50% of patients with a wide range of ataxia-related phenotypes
Authors: Sun, Miao; Johnson, Amy Knight; Nelakuditi, Viswateja; Guidugli, Lucia; Fischer, David; Arndt, Kelly; Ma, Lan; Sandford, Erin; Shakkottai, Vikram; Boycott, Kym; Chardon, Jodi Warman; Li, Zejuan; del Gaudio, Daniela; Burmeister, Margit; Gomez, Christopher M.; Waggoner, Darrel J.; Das, Soma
Journal: GENETICS IN MEDICINE Volume 21 Issue 1
Date of Publication:2019
Abstract:
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.