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Comment & Response
August 2014

GNAL Mutations and Dystonia—Reply

Author Affiliations
  • 1Institute of Neurogenetics, University of Luebeck, Luebeck, Germany
  • 2Department of Neurogenetics, Kolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney, Sydney, Australia
  • 3Department of Neuroscience, The Scripps Research Institute, Jupiter, Florida
JAMA Neurol. 2014;71(8):1053-1054. doi:10.1001/jamaneurol.2014.1509

In Reply We thank Erro and colleagues for their appraisal of our article1 and wish to expand on their 2 major comments. First, they noted that the prevalence of GNAL mutations in dystonia may have initially been overestimated2 and pointed out that all of the follow-up studies reported lower frequencies. At a critical recalculation, these frequencies may even be lower than indicated in the Table by Erro and colleagues: Because Saunders-Pullman et al3 included known mutation-positive families, the correct estimation would exclude those families, resulting in a frequency estimate of 1 of 38 (2.6%). Furthermore, one of the reported variants in the study by Miao et al4 is intronic without affecting a conserved splice site and should not be counted (corrected frequency: 1 of 59 = 1.7%). Thus, in the follow-up studies, the frequency of GNAL mutations was less than 2.6%.3 This is indeed considerably lower than the initially assumed 15% in selected familial cases.2 However, even a percentage of maybe 1% would imply that each larger dystonia center (>100 patients) would statistically deal with at least 1 GNAL mutation carrier. This is specifically relevant because GNAL is the first known genetic cause of adult-onset dystonia.

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