Segregation of HLA in sibs with cleft lip or cleft lip and palate: evidence against genetic linkage

The segregation of HLA haplotypes (A, B, and C loci) was studied in eight families in which two sibs were affected with cleft lip or cleft lip and palate. HLA typing was performed in parents and sibs and in specific cases, other family members. Segregation of HLA haplotypes did not differ significantly from random Mendelian expectation. Three of the eight affected sib pairs differed in both HLA haplotypes, which is not expected if there is close linkage with susceptibility to clefting. Thus, it is very unlikely that spontaneous cleft lip or cleft lip and palate is closely linked to HLA.