CONCORDANCE OF 21-HYDROXYLASE GENE RATIO, HUMAN-LEUKOCYTE ANTIGEN HAPLOTYPING AND ADRENAL TESTING RESULTS IN A FAMILY WITH LATE-ONSET ADRENAL-HYPERPLASIA

Late-onset adrenal hyperplasia (LOAH) due to 21-hydroxylase (21-OH) de ficiency is one of the most common autosomal recessive disorders. Ther e appear to be two 21-OH genes, CYP21A (a pseudogene) and CYP21B (the functional gene), which lie in close proximity to the human leukocyte antigen (HLA) encoding region on the short arm of chromosome 6. While the CYP21A/CYP21B ratio is normally 1:1, ratio abnormalities are frequ ent in LOAH, suggesting gene deletion, duplication or conversion. The objective of this study was to determine whether an abnormal CYP21A/CY P21B ratio could predict carriers of LOAH, as determined by endocrine and HLA results. The probands appear to be compound heterozygotes carr ying a 21-OH gene for LOAH and a deletion of the homologous gene. Howe ver, concordance between an abnormal 21-OH gene ratio and the inherita nce of the LOAH gene does not appear to be complete, as demonstrated b y this family study. Further studies of the feasibility of screening c arriers for 21-OH deficiencies with the CYP21A/CYP21B ratio or other m olecular probes must be performed.