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Polymorphisms in the xylosyltransferase genes cause higher serum XT-I activity in patients with pseudoxanthoma elasticum (PXE) and are involved in a severe disease course
  1. S Schön1,
  2. V Schulz1,
  3. C Prante1,
  4. D Hendig1,
  5. C Szliska2,
  6. J Kuhn1,
  7. K Kleesiek1,
  8. C Götting1
  1. 1Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Bad Oeynhausen, Germany
  2. 2Dermatologische Klinik, Krankenhaus Bethesda, Freudenberg, Germany
  1. Correspondence to:
 Christian Götting
 Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Georgstraße 11, 32545 Bad Oeynhausen, Germany;cgoetting{at}


Background: Pseudoxanthoma elasticum (PXE) is a heritable connective tissue disorder caused by mutations in the ABCC6 gene. Fragmentation of elastic fibres and deposition of proteoglycans result in a highly variable clinical picture. The altered proteoglycan metabolism suggests that enzymes from this pathway function as genetic co-factors in the severity of PXE. Therefore, we propose the XYLT genes encoding xylosyltransferase I (XT-I) as the chain-initiating enzyme in the biosynthesis of proteoglycans and the highly homologous XT-II as potential candidate genes.

Methods: We screened all XYLT exons in 65 German PXE patients using denaturing high performance liquid chromatography and analysed the influence of the variations on clinical characteristics.

Results: We identified 22 variations in the XYLT genes. The missense variation p.A115S (XT-I) is associated with higher serum XT activity (p = 0.005). The amino acid substitution p.T801R (XT-II; c.2402C>G) occurs with significantly higher frequency in patients under 30 years of age at diagnosis (43% v 26%; p = 0.04); all PXE patients with this variation suffer from skin lesions compared to only 75% of the wild type patients (p = 0.002). c.166G>A, c.1569C>T, and c.2402C>G in the XYLT-II gene were found to be more frequent in patients with higher organ involvement (p = 0.04, p = 0.01, and p = 0.02, respectively).

Conclusions: Here we show for the first time that variations in the XYLT-II gene are genetic co-factors in the severity of PXE. Furthermore, the higher XT activity in patients with the exchange p.A115S (XT-I) indicates that this polymorphism is a potential marker for increased remodelling of the extracellular matrix.

  • ABCC6, ATP-binding cassette transporter subfamily C member 6
  • DHPLC, denaturing high performance liquid chromatography
  • GAG, glycosaminoglycan
  • MRP6, transmembrane transporter protein multidrug resistance-associated protein 6
  • PXE, pseudoxanthoma elasticum
  • RFLP, restriction fragment length polymorphism
  • SNP, single nucleotide polymorphism
  • UTR, untranslated region
  • XT, xylosyltransferase (protein)
  • XYLT, xylosyltransferase (gene)
  • polymorphisms
  • proteoglycan
  • pseudoxanthoma elasticum
  • xylosyltransferase

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  • Published Online First 12 April 2006

  • Competing interests: none declared