Variants of the CYP21A2 and CYP21A1P genes in congenital adrenal hyperplasia

More than 90% of congenital adrenal hyperplasia cases are caused by mutation of the CYP21A2 gene which converted from the CYP21A1P pseudogene. Sizes of the 3.7-kb Taql-produced fragment that exists downstream of the TNXB gene, representing the CYP21A2, and the 3.2-kb Taql-produced fragment that exists downstream of the XA gene, representing the CYP2IAIP pseudogene, are used as size markers in the restriction fragment length polymorphism (RFLP) analysis. However, the size of and location for distinguishing these two genes might not be completely precise or reliable. Recent studies indicated that the 3.2-kb Taql fragment may include multiple variants of chimeric CYP21A1P/CYP21A2 genes, a haplotype with dual mutations of IVS2-12A/C>G and 707-714del, and a functional CYP21A2 gene caused by small-scale conversions of the 5' end of the CYP21A1P sequence. In addition, a 3.7-kb Taql fragment with more than 4 haplotypes of CYP21A2-like downstream of the TNXA gene and a 6.2-kb Taql fragment of the CYP21A2 that results from a nucleotide mutation in the 3' end sequence were also identified. Accordingly, these structural variants reveal that traditional recognition of these two genes based on the Taql fragment size analysis may lead to misinterpretation and increasingly interfere with the molecular diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. (C) 2013 Elsevier B.V. All rights reserved.