The R156H variation in IL-12Rβ1 is not a mutation
1 Department of Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
2 Department of Translational Medical Sciences, “Federico II” University, Naples, Italy
3 International Institute of Genetics and Biophysics, CNR, Naples, Italy
Italian Journal of Pediatrics 2013, 39:12 doi:10.1186/1824-7288-39-12Published: 14 February 2013
Palamaro et al. describe a child with recurrent bronchopneumonia and very high IgE levels in which a variation, R156H, was found in the IL12RB1 gene that encodes the IL-12Rβ1 chain. Based on the absence of this variation in 50 unrelated individuals they conclude it is a mutation. We (van de Vosse and van Dissel) feel there is no reason to suspect a defect in IL-12 signaling based on the clinical data, nor evidence for a functional defect in IL-12 signaling in this patient. In addition, the variation is not novel and known as a polymorphism. Without any functional evidence that R156H is a mutation, the current claim is not substantiated.
Palamaro et al. respond to argue that the amino acid substitution, R156H described in the described case exerts a summatory effect, as a genetic cofactor, along with an additional and still unidentified molecular alteration of the same pathway.