RYK Is Not Mutated in Autosomal Dominant Robinow Syndrome

It was with great interest that we read the recent article published by Andre et al. (1) describing the role of Ryk in regulating planar cell polarity (PCP) signaling. This article brings relevant information about the transduction of Wnt5a signaling by the Ryk-Vangl2 complex. Based on their results, the authors propose that mutations in the RYK gene might be involved in the etiology of Robinow syndrome. We have previously described mutations in the WNT5A gene in patients with autosomal dominant Robinow syndrome (DRS) (2). At that time, considering the similarities between the Wnt5a and Ryk knock-out mice (2, 3), we screened 24 patients diagnosed with DRS for mutations in exons 2–16 of RYK. No pathogenic mutations were identified suggesting that mutations in RYK are not a major cause of DRS. However, since DRS appears to be highly heterogeneous with only one familial and one sporadic case reported to carry WNT5A mutations, we cannot definitely exclude RYK as a candidate for a minority of cases. The identification of a major causative gene for DRS by other approaches such as exome sequencing may shed light on the etiology of DRS and contribute to a better understanding of the PCP pathway.