Diagnosis of classical steroid 21-hydroxylase deficiency using an HLA-B locus-specific DNA-probe

The HLA-B and steroid 21-hydroxylase loci are known to be closely linked. Restriction fragment length polymorphisms seen after digestion of genomic DNA with MspI and TaqI with the HLA-B locus-specific DNA-probe, pHLA-1.1, were examined in 7 nuclear families with classical steroid 21-hydroxylase deficiency. In each family 2 polymorphic hybridizing bands (corresponding to the 2 HLA-B genes) were seen. In all families, TaqI-generated polymorphisms allowed for identification of children previously shown on clinical and biochemical criteria to be affected by 21-hydroxylase deficiency from their unaffected sibs. The results were in complete agreement with the clinical diagnoses. Among the unaffected children, carriers could be distinguished from non-carriers in all cases by TaqI polymorphisms. MspI-generated polymorphisms allowed for full identification of genotypes in 5 families. In one family, MspI-generated polymorphisms could be used to identify affected from unaffected children, but could not distinguish between carriers and non-carriers. In another family, no identification of genotypes was possible by MspI-generated polymorphisms alone. The HLA-B locus-specific DNA-probe, pHLA-1.1, can be used for diagnosis and genotyping of individuals from families with 21-hydroxylase deficiency. This technique can be used as an alternative to HLA-serotyping, or in situations where HLA-serotyping is technically difficult, for example in chorionic villus samples.