Abstract
Steroid 21-hydroxylase deficiency is the most prominent cause of congenital adrenal hyperplasia (CAH). Patients suffer from virilization, and in severe cases, from salt loss caused by lack of aldosterone. The CYP21 gene, encoding steroid 21-hydroxylase, and the highly homologous pseudogene CYP21P are located within the human MHC on chromosome 6p21.3, the usual arrangement being centromere - HLA-DP, -DQ, -DR - CYP21-complement C4B-CYP21P-complement C4A - tumour necrosis factor (TNF) genes - HLA-B. -C. -A. We investigated a CAH family (father, mother, patient, three healthy sibs) using 21-hydroxylase and complement C4 probes and allele specific oligonucleotides to detect specific mutations. Oligonucleotide hybridization showed that the patient inherited the Ile172->Asn mutation. characteristic of “simple virilizing” CAH. from the mother. On the other chromosome, the CYP21 gene was deleted: however, this defect was not found in DNA from the father. Paternity was confirmed using VNTR probes. Establishment of HLA-B. TNF and HLA-DQα markers showed that the patient had the HLA-B and TNF genes from one paternal chromosome and the HLA-DQα gene from the other. Apparently, a paternal meiotic recombination event has eliminated the CYP21 gene (as well as the adjacent C4B gene), contributing to steroid 21-hydroxylase deficiency in the patient.
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Koppens, P., Hoogenboezem, T., Smeets, H. et al. 56 A RECOMBINATION EVENT CAUSING A DE NOVO DELETION OF THE STEROID 21-HYDROXYLASE GENE CYP21. Pediatr Res 36, 12 (1994). https://doi.org/10.1203/00006450-199407000-00056
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DOI: https://doi.org/10.1203/00006450-199407000-00056