Steroid 21-hydroxylase deficiency, the primary cause of congenital adrenal hyperplasia, is caused by defects of the CYP21A2 gene. As a complement to hormonal measurements, mutation analysis of CYP21A2 is an important tool in the diagnosis of steroid 21-hydroxylase deficiency. Contemporary mutation-detection protocols based on the polymerase chain reaction often depend on the assumption that no more than one CYP21A2 gene is present on each chromosome 6. We describe three haplotypes with two CYP21A2 genes on the same chromosome, with defects typical of salt-losing steroid 21-hydroxylase deficiency in one of these genes, but not necessarily in the other. The frequency of these haplotypes in the general population is 6/365 (1.6%), so they are no less common than other haplotypes that indeed carry steroid 21-hydroxylase deficiency. Chromosome that carry two CYP21A2 genes therefore represent a significant pitfall in the molecular diagnosis of steroid 21-hydroxylase deficiency. We recommend that, whenever CYP212A mutation analysis of an individual who is not a known carrier of steroid 21-hydroxylase deficiency is performed, the overall structure of the CYP21/C4 region (the RCCX area) is determined by haplotyping to avoid erroneous assignment of carrier status.,
Human Genetics
Department of Pediatrics

Koppeans, P., Hoogenboezem, T., & Degenhart, H. (2002). Duplication of the CYP21A2 gene complicates mutation analysis of steroid 21-hydroxylase deficiency: Characteristics of three unusual haplotypes. Human Genetics, 111(4-5), 405–410. doi:10.1007/s00439-002-0810-7