Population and family studies of HLA in Japanese with cleft lip and cleft palate.

Population and family studies of HLA were performed in Japanese patients with cleft lip and/or cleft palate (CL/P). Frequency of HLA-Cw 7 was significantly increased in cleft lip (CL) patients (37.5%) and cleft palate (CP) patients (37.8%) but was not increased in cleft lip and palate (CLP) patients (17.5%), compared with control subjects (13.3%). However, the intensities of the associations were not great (relative risk = 4.0). The affected sib pairs method was studied in 13 families with CL- or CLP-affected sib pairs and 10 families with CP-affected sib pairs. However, in both groups of families the distributions of HLA haplotypes in affected sib pairs did not significantly differ from random Mendelian expectation. Thus, HLA-linked major genes (loci) which determine the development of CL/P were not found. These results seem indirectly to support the multifactorial theory of CL/P, but does not exclude other possible genetic mechanisms.