Susceptibility to phenytoin-induced cleft lip with or without cleft palate: Many genes are involved

Abstract

In a search for genetic differences in susceptibility to cleft lip with or without cleft palate [CL(P)], congenic and recombinant inbred strains of mice were treated with phenytoin or control injections. Of six loci tested, five were found to affect susceptibility to phenytoin-induced and/or sporadic CL(P): (1) the major histocompatibility locus, H-2; (2) the locus controlling β2-microglobulin, B2m; (3) a locus controlling β-glucuronidase, Gus; (4) the locus controlling N-acetyl transferase, Nat; and (5) the locus for brown pigmentation, b. B2m and Gus only affected the sporadic incidence of CL(P), while the b locus only affected phenytoin-induced incidence of CL(P). Three of these loci are also known to affect glucocorticoid-induced isolated cleft palate (CP), but different alleles of the loci are involved. Phenytoin did not affect levels of adenosine 3′,5′-cyclic monophosphate (cAMP) in palates and tongues of day 15 fetuses. A comparison of glucocorticoid receptor parameters with the incidence of phenytoin-induced CL(P) found no correlation. © 1987, Cambridge University Press. All rights reserved.