A LOCUS IN 2P13-P14 (OFC2), IN ADDITION TO THAT MAPPED IN 6P23, IS INVOLVED IN NONSYNDROMIC FAMILIAL OROFACIAL CLEFT MALFORMATION

An allelic association between the transforming growth factor alpha ge ne (TGFA) situated in the chromosome 2p13 region and nonsyndromic clef t lip with or without cleft palate, also named orofacial cleft (OFC), was found in several population studies. However, no linkage between g ene and malformation has shown up until now, probably due to the prese nce of genetic heterogeneity and the small sample size analyzed. Previ ously, we employed a collection of 38 OFC families to demonstrate link age to the 6p23 chromosome region with the presence of genetic heterog eneity. In the present study we tested whether, in the same sample, li nkage between OFC and markers on 2p13 could be determined. Evidence fo r genetic heterogeneity in our family set was apparent, by both pairwi se and multipoint linkage analyses. Moreover, lod scores >3 were found for marker D25378 when families linked to the 6p23 markers were analy zed. Taken together these results indicate a role for the TG;FA, or fo r another gene physically close to it, and suggest an interaction betw een two different genes, OFC1 and OFC2, mapped in 6p23 and 2p13, respe ctively, in the development of the cleft. (C) 1998 Academic Press.