The HLA system and the genetics of juvenile diabetes mellitus

Eighteen families with a total of 68 children were completely typed for HLA-A, B, C, D and Bf. With only one exception, all affected children within each family with 2 or more diabetic siblings, shared both HLA-D alleles indicating that J.D.M. is a recessive trait. Since half of the siblings who are HLA-D identical to the first affected child developed J.D.M. (as is the case of monozygotic twins), the gene(s) in question is most likely the sole genetic requirement for this disease and has a penetrance of 50%. No evidence of association between J.D.M. and B8, Dw3 or Bw15 was observed by analyzing the segregation of J.D.M. and of each of the above HLA antigens in informative families. A total of 9 out of 68 children bore a recombinant HLA haplotype. This increased rate of crossing-over in J.D.M. seems to require a single J.D.M. gene since the parents (9) in whom recombinations occurred were non-diabetic. No association was seen between the presence of the disease and the existence of a recombinant hoplotype.