The chimeric CYP21P/CYP21 gene and 21-hydroxylase deficiency

J Hum Genet. 2004;49(2):65-72. doi: 10.1007/s10038-003-0115-2. Epub 2004 Jan 17.

Abstract

The chimeric CYP21P/CYP21 gene is a consequence of a 26- or 32-kb deletion in the C4-CYP21 repeat module of CYP21P, tenascin A ( XA), serine/threonine nuclear protein kinase ( RP2), and the C4B and CYP21 genes in congenital adrenal hyperplasia (CAH) with steroid 21-hydroxylase deficiency. To date, there have been three distinct chimeras found in CAH patients in ethnic Chinese. Initiation for production of these molecules is proposed to be chi-like sequences and a minisatellite consensus existing in several noncoding regions in CYP21 genes. These molecules have the 5' end of the CYP21P-specific sequence in common but differ in the 3' end of CYP21-specific genes. In addition, there appears to be a 3.2-kb fragment generated by Taq I digestion, which leads to allele dropout in PCR amplification for detecting the aberrant splicing site of the IVS2 -12A/C>G mutation at nucleotide (nt) 655 in the CYP21 gene. Therefore, the chimeric CYP21P/CYP21 cannot be detected by conventional methods. It has been demonstrated that a PCR product amplified with allele-specific primers covering tenascin B ( TNXB) to the 5' end of the CYP21 gene combined with Southern analysis by Ase I and Nde I digestion may be used for identifying the chimera in the CYP21 gene.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenal Hyperplasia, Congenital / genetics*
  • Base Sequence
  • China
  • Chromosomes, Human, Pair 6 / genetics
  • Complement C4b / genetics
  • DNA Primers
  • Ethnicity
  • Humans
  • Pseudogenes / genetics*
  • Recombinant Fusion Proteins / genetics
  • Recombination, Genetic / genetics*
  • Sequence Deletion*
  • Steroid 21-Hydroxylase / genetics*

Substances

  • DNA Primers
  • Recombinant Fusion Proteins
  • Complement C4b
  • Steroid 21-Hydroxylase