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Mapping of a de novo unequal crossover causing a deletion of the steroid 21-hydroxylase (CYP21A2) gene and a non-functional hybrid tenascin-X (TNXB) gene
  1. P F J Koppens1,
  2. H J M Smeets2,
  3. I J de Wijs3,
  4. H J Degenhart4
  1. 1Department of Paediatrics, Erasmus MC Sophia, Rotterdam, The Netherlands
  2. 2Clinical Genetics Centre Maastricht, Maastricht, The Netherlands
  3. 3Department of Human Genetics, University Medical Centre Nijmegen, Nijmegen, The Netherlands
  4. 4Department of Paediatrics, Erasmus MC Sophia, Rotterdam, The Netherlands
  1. Correspondence to:
 Dr P F J Koppens, Erasmus MC, University Medical Centre, Rotterdam, Laboratory of Paediatrics, Room Ee1502b, PO Box 1738, 3000 DR Rotterdam, The Netherlands; 

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In the human genome, the major histocompatibility complex class III region on chromosome 6p21.3 stands out as an area of remarkably high gene density.1,2 Within this region, a section of particular complexity centres around the C4 genes, which encode the fourth component of complement.3–7 Centromeric to C4 lies the CYP21A2 gene, which encodes steroid 21-hydroxylase, a key enzyme in the biosynthesis of cortisol and aldosterone.4,8,9 The TNXB gene, which encodes the extracellular matrix protein tenascin-X, lies centromeric to CYP21A2 and is transcribed from the opposite strand.10–12 Telomeric to C4 lies the RP1 gene, encoding a putative serine/threonine kinase.13–15 A typical chromosome 6 carries a duplication of an area of approximately 30 kb encompassing the entire C4 and CYP21 genes4,8 plus small truncated sections of RP and TNX.10–14 This tandem repeat has been named the RCCX module after its four constituent genes.7,14,16,17 In most white populations, about 70% of all haplotypes have a bimodular arrangement similar to the one shown in fig 1. The complex genetics of this region, and the activities and clinical significance of the proteins encoded here, have been the subject of several recent reviews.7,18–21

Figure 1

Overview of a typical C4/CYP21 area within the MHC class III region showing two RCCX modules as found on most chromosomes. TNXB is the full size 68 kb gene for tenascin-X. TNXA (also known as XA) is a truncated pseudogene of 5.7 kb that not only lacks most of the coding sequence of TNXB but also has a 120 bp deletion (indicated by the small triangle) spanning an exon-intron boundary.10,12,17CYP21A2 (also known as CYP21B) is the active steroid 21-hydroxylase gene; CYP21A1P (also known as …

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