We report on a combined study of 32 families from NY and Zurich with a total of 46 patients with CAH.It was found that all patients were HLA genotypically different from the healthy sibs and that 2 or more affected children in the same sibship were HLA identical. Lod Score analysis demonstrated a peak Lod Score of 4.2 for the recombinant fraction (Θ)≃0.00 between HLA-B and 21-OH-def. Close genetic linkage between HLA-B and 21-OH-def. was thus established. No HLA-A,B or C antigen was selectively increased among the 34 unrelated patients. These studies provide the basis for utilization of HLA genotyping in high risk families to identify heterozygous carriers of the 21-OH-def. gene among sibs and other relatives. On the basis of these studies it can be predicted that 31 sibs were heterozygous carriers and 11 sibs were genetically unaffected for the enzyme deficiency. Prenatal diagnosis of the disease in high risk families by HLA typing of cultured amniotic cells may be possible. This is the first example in which an enzymatic deficiency of steroid biosynthesis has been shown to be closely linked to HLA.
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Levine, L., Zachmann, M., New, M. et al. Close Genetic Linkage Between Congenital Adrenal Hyperplasia (21-hydroxylase deficiency) and HLA. Pediatr Res 12, 1088 (1978). https://doi.org/10.1203/00006450-197811000-00040