Linkage analysis of candidate endothelin pathway genes in nonsyndromic familial orofacial cleft

There is good evidence from linkage analysis and mouse model knockouts that the endothelin-1 gene (EDN1) is a good candidate for non-syndromic orofaci al cleft (OFC) disease. EDN1 maps to the chromosomal region of the OFC1 loc us in 6p23. Therefore we have examined three other candidate genes in the e ndothelin 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 diso rder is not linked to chromosome 6p23. The total lod score for these 9 mult iplex families never exceeded -2.00 and thus our data suggest that EDN1 and related genes are not involved in non-syndromic familial CEC.