Intra-HLA recombinations localizing the 21-hydroxylase deficiency gene within the HLA complex.
Close linkage between HLA and the gene for 21-OH deficiency causing congenital virilizing adrenal hyperplasia (CVAH) has been well documented. HLA-A/B and HLA/GLO recombination data placed the CVAH gene within the HLA-A to GLO interval, with CVAH invariably segregating with HLA. HLA-A,B,C,DR and GLO typing and ACTH stimulation to determine carrier status was done on seven families. Carrier status correlated with the appropriate HLA haplotypes in all offspring, with two exceptions. Two intra-HLA recombinants were detected in one three-generation family. The father of the proband is homozygous for HLA-A2,Cw2,B27 but is a DR2/DR4 heterozygote. The CVAH gene segregated with DR2 in all but one of his offspring who is a carrier and is DR4. This finding is consistent with recombination between the CVAH gene and DR. Study of the father's family confirmed synteny of the CVAH gene and DR2. Three of four sibs of the father inherited this haplotype and were CVAH carrier, as was the paternal grandmother, whose other haplotype was A1, Bw44,DR1. One of the father's sibs was shown serologically to be a HLA-B/D maternal recombinant and a noncarrier. she inherited the A1,Bw44 of one maternal haplotype, but the DR2 of the other. In both recombinants in this family the CVAH gene segregated with the A to B interval, separate from D. While we cannot determine whether the CVAH gene is in the HLA-A to B or B to D interval, this is the first report of two intra-HLA recombinations in one family that unequivocally map the CVAH gene inside HLA-D.
D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D005260:Female; D006680:HLA Antigens / Q000235:genetics*; D006238:Haploidy; D006650:Histocompatibility Testing; D006801:Humans; D007791:Lactoylglutathione Lyase; D007959:Lymphocyte Culture Test, Mixed; D008285:Major Histocompatibility Complex; D008297:Male; D011995:Recombination, Genetic; D013255:Steroid 21-Hydroxylase / Q000235:genetics; D013250:Steroid Hydroxylases / Q000172:deficiency*
D006680:HLA Antigens; D000324:Adrenocorticotropic Hormone; D013250:Steroid Hydroxylases; D013255:Steroid 21-Hydroxylase; D007791:Lactoylglutathione Lyase