Linkage studies between HLA-A,B,D alleles and congenital adrenal hyperplasia (CAH)

Abstract

The observation by Dupont et al.of close linkage between CAH and the HLA-complex prompted us to study the inheritance of HLA-haplotypes and the deficiency of C21-Hydroxylase(C21-H) in 12 families with CAH children.All family members were tested for CAH heterozygosity by the increase of plasma 17-OHP after ACTH stimulation.An increase of 17-OHP > 200 ng/dl was taken as evidence for CAH-heterozygosity.HLA-A,B,D typing was done by established serological and cellular methods.In 3 families with 2 CAH cases, we found identical HLA-A,B,D in the affected siblings. There was a good correlation between the results of the heterozygosity test and the segregation of HLA-haplotypes, in some cases over 3 generations.The distribution of HLA-A,B,D alleles in the 12 unrelated CAH-patients was not significantly different from controls,indicating that there is no positive association between C21-H deficiency and antigens of the HLA-series.Our data support the concept of close linkage of CAH and HLA allowing more precise prenatal diagnosis of CAH and identification of heterozygotes.