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Coupling of HLA-A3,Cw6,Bw47,DR7 and a Normal CA21HB Steroid 21-Hydroxylase Gene in the Old Order Amish^*

PATRICIA A. DONOHOUE, CORNELIS VAN DOP, CLAUDE J. MIGEON, ROBERT H. MCLEAN and WILMA B. BIAS

Divisions of Pediatric Endocrinology (P.A.D., C. V.D., C.J.M.), Pediatric Nephrology (R.H.M.), and Medical Genetics (W.B.B.), The Johns Hopkins University School of Medicine Baltimore, Maryland 21205

Address requests for reprints to: Dr. Patricia A. Donohoue, CMSC 3–110, The Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, Maryland 21205.

HLA-Bw47, a rare human histocompatibility antigen, occurs in strong linkage disequilibrium with HLA-A3,Cw6,DR7 and salt-losing congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency and is associated with a contiguous deletion of the active CA21HB gene and the C4B complement gene. We studied the HLA-A3,Cw6,Bw47,DR7 haplotype in 10 subjects of the Old Order Amish of Lancaster County in Pennsylvania and found that this haplotype, which occurs with a similar frequency in this group as in the general caucasoid population, has C4B and CA21HB genes. These C4B and CA21HB genes are expressed as assessed by C4 typing and iv ACTH testing, respectively. Serological studies indicate that the HLA-D loci of this Amish haplotype are the same as those in patients with HLA-Bw47 and CAH, but different from HLA-D loci coupled to HLA-B13, which some workers have proposed is the progenitor genotype for HLA-Bw47. Our studies demonstrate that 1) HLA-Bw47 is not an invariant marker for saltlosing CAH due to 21-hydroxylase deficiency, and 2) the HLA-Bw47 phenotype coupled to CAH is not derived from the HLA-B13 genotype by a single mutation.

^* This work was supported by NIH Grants AM-36085, DK-00180, DK-31920, DK-07116, and RR-00722.

Recipient of a Basil O'Connor Research Grant from the March of Dimes. Current address: Howard Hughes Medical Institute at Children's Hospital, Boston, Massachusetts 02115.

Received April 24, 1987.