SCA23 and prodynorphin: is it time for gene retraction?

Reply: SCA23 and prodynorphin: is it time for gene retraction?

“…Pedroso et al also claim all reported PDYN variants to be disease-causing, which is not true. We clearly mention in the work described in Jezierska et al (2013), and not in Fogel et al (2012) as claimed by Pedroso et al (2016), that the c.616C 4 T, p.Arg206Cys variant (MAF ExaC; 0.0001318) and the c.617G 4 A, p.Arg206His variant might well be rare polymorphisms as the p.Arg206Cys variant did not have any effect on processing of PDYN, and no co-segregation could be detected for p.Arg206His (Jezierska et al, 2013). Therefore, we did not conclude that these variants exhibit pathogenic effects.…”

“…We therefore must rely heavily on in silico prediction programs and the information found in large genetic databases such as ExAC [Exome Aggregation Consortium (ExAC), Cambridge, MA] (http://exac.broadinstitute.org) to predict the pathogenicity of variants. The letter from Pedroso et al (2016) addresses this problem. Pedroso et al (2016) state that many of the reported SCA23 mutations in PDYN are present in ExAC and suggest that this brings into question the validity of PDYN as the disease-causing gene for SCA23.…”

“…The letter from Pedroso et al (2016) addresses this problem. Pedroso et al (2016) state that many of the reported SCA23 mutations in PDYN are present in ExAC and suggest that this brings into question the validity of PDYN as the disease-causing gene for SCA23. They point out that the SCA23 mutations were detected in 37 of 60 700 individuals in ExAC, a database that was founded in 2014, 4 years after our original SCA23 report was published, when none of these PDYN variations had been detected in controls or any genetic database, supporting our conclusion that PDYN is the SCA23 disease gene.…”