IRF6 mutations may not be a major cause of Van der Woude syndrome in India

Abstract

We read with interest the article by GB Ferrero et al. on Vander Woude syndrome (VWS) reporting a novel mutation [2]in the IRF6 gene coding region. Nearly 100 mutations inthe coding region of the gene have been reported fromseveral populations in different geographical regions of theglobe. So far, IRF6 is the only gene shown to be associatedwith VWS as a dominant trait with variable penetrance andexpressivity. However, direct sequencing of all codingregions and exon–intron boundaries of the IRF6 gene havenot shown any mutation in an Indian cohort (n=13) [1].Another Indian study of a VWS pedigree conducted by theauthors also corroborates the findings that critical region ofthe 1q32–q41 may not be causal for VWS in multi-ethnicand diverse Indian populations [3]. As VWS is the mostcommon form of syndromic clefting, the possibility ofstochastic factors modifying the expression of the syndromecannot be denied. However, the tendency towards apublication bias and the “file drawer effect” may sometimesresult in inadequate outcome reporting. Published studiesmay not be truly representative of all valid studiesundertaken, and this bias may distort meta-analyses andsystematic reviews of large numbers of studies—on whichevidence-based medicine increasingly relies. This furthercompounds the genetic complexity of the one of the mostcommon orofacial clefting syndromes, which needs to bestudied in greater depth before any conclusion can bedrawn. Therefore the authors are of the opinion that it is toopremature to use only IRF6 mutations as diagnostic/predictive tests which are being offered by some companieswith vested interests.