There is good evidence from linkage analysis and mouse model knockouts that the endothelin-1
gene (EDN1) is a good candidate for non-syndromic orofacial cleft (OFC) disease. EDN1 maps to the
chromosomal region of the OFC1 locus in 6p23. Therefore we have examined three other candidate
genes in the endothelin pathway (ECE1, EDNRA and EDNRB, which map to chromosomes 1, 4 and
13 respectively) in a linkage study of 9 families with OFC, where the disorder is not linked to
chromosome 6p23. The total lod score for these 9 multiplex families never exceeded −2.00 and thus
our data suggest that EDN1 and related genes are not involved in non-syndromic familial OFC.