The Journal of Pediatrics
Volume 154, Issue 3 , Pages 431-437 , March 2009

Birth Prevalence of Homocystinuria in Central Europe: Frequency and Pathogenicity of Mutation c.1105C>T (p.R369C) in the Cystathionine Beta-Synthase Gene

Received 19 May 2008 ,Revised 11 August 2008 ,Accepted 4 September 2008.

References 

  1. Mudd SH, Levy HL, Kraus JP. Disorders of transsulfuration. In:  Scriver CR,  Beaudet AL,  Sly WS,  Valle D,  Childs B,  Vogelstein B editor. The Metabolic and Molecular Bases of Inherited Disease. 8 ed.. New York: McGraw-Hill; 2001;p. 2007–2056
  2. Kraus JP, Kozich V. Cystathionine-beta-synthase and its deficiency. In:  Carmel R,  Jakobsen DW editor. Homocysteine in Health and Disease. Cambridge: Cambridge University Press; 2001;p. 223–243
  3. Gaustadnes M, Rudiger N, Rasmussen K, Ingerslev J. Familial thrombophilia associated with homozygosity for the cystathionine beta-synthase 833T—>C mutation. Arterioscler Thromb Vasc Biol. 2000;20:1392–1395
  4. Gaustadnes M, Wilcken B, Oliveriusova J, McGill J, Fletcher J, Kraus JP, et al. The molecular basis of cystathionine beta-synthase deficiency in Australian patients: genotype-phenotype correlations and response to treatment. Hum Mutat. 2002;20:117–126
  5. Linnebank M, Junker R, Nabavi DG, Linnebank A, Koch HG. Isolated thrombosis due to the cystathionine beta-synthase mutation c.833T>C (1278T). J Inherit Metab Dis. 2003;26:509–511
  6. Maclean KN, Gaustadnes M, Oliveriusova J, Janosik M, Kraus E, Kozich V, et al. High homocysteine and thrombosis without connective tissue disorders are associated with a novel class of cystathionine beta-synthase (CBS) mutations. Hum Mutat. 2002;19:641–655
  7. Wilcken B, Wiley V, Hammond J, Carpenter K. Screening newborns for inborn errors of metabolism by tandem mass spectrometry. N Engl J Med. 2003;348:2304–2312
  8. Naughten ER, Yap S, Mayne PD. Newborn screening for homocystinuria: Irish and world experience. Eur J Pediatr. 1998;157(Suppl 2):S84–S87
  9. Gaustadnes M, Ingerslev J, Rutiger N. Prevalence of congenital homocystinuria in Denmark. N Engl J Med. 1999;340:1513
  10. Sokolova J, Janosikova B, Terwilliger JD, Freiberger T, Kraus JP, Kozich V. Cystathionine beta-synthase deficiency in Central Europe: discrepancy between biochemical and molecular genetic screening for homocystinuric alleles. Hum Mutat. 2001;18:548–549
  11. Linnebank M, Homberger A, Junker R, Nowak-Goettl U, Harms E, Koch HG. High prevalence of the I278T mutation of the human cystathionine beta-synthase detected by a novel screening application. Thromb Haemost. 2001;85:986–988
  12. Refsum H, Fredriksen A, Meyer K, Ueland PM, Kase BF. Birth prevalence of homocystinuria. J Pediatr. 2004;144:830–832
  13. Kluijtmans LA, Boers GH, Kraus JP, van den Heuvel LP, Cruysberg JR, Trijbels FJ, et al. The molecular basis of cystathionine beta-synthase deficiency in Dutch patients with homocystinuria: effect of CBS genotype on biochemical and clinical phenotype and on response to treatment. Am J Hum Genet. 1999;65:59–67
  14. Kim CE, Gallagher PM, Guttormsen AB, Refsum H, Ueland PM, Ose L, et al. Functional modeling of vitamin responsiveness in yeast: a common pyridoxine-responsive cystathionine beta-synthase mutation in homocystinuria. Hum Mol Genet. 1997;6:2213–2221
  15. Kozich V, Kraus JP. Screening for mutations by expressing patient cDNA segments in E. coli: homocystinuria due to cystathionine beta-synthase deficiency. Hum Mutat. 1992;1:113–123
  16. Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265–275
  17. Kraus JP. Cystathionine beta-synthase (human). Methods Enzymol. 1987;143:388–394
  18. Meier M, Oliveriusova J, Kraus JP, Burkhard P. Structural insights into mutations of cystathionine beta-synthase. Biochim Biophys Acta. 2003;1647:206–213
  19. Yamanishi M, Kabil O, Sen S, Banerjee R. Structural insights into pathogenic mutations in heme-dependent cystathionine-beta-synthase. J Inorg Biochem. 2006;100:1988–1995
  20. Brown CR, Hong-Brown LQ, Welch WJ. Correcting temperature-sensitive protein folding defects. J Clin Invest. 1997;99:1432–1444
  21. Waters PJ. How PAH gene mutations cause hyper-phenylalaninemia and why mechanism matters: insights from in vitro expression. Hum Mutat. 2003;21:357–369
  22. Mandey SH, Schneiders MS, Koster J, Waterham HR. Mutational spectrum and genotype-phenotype correlations in mevalonate kinase deficiency. Hum Mutat. 2006;27:796–802
  23. Peterschmitt MJ, Simmons JR, Levy HL. Reduction of false negative results in screening of newborns for homocystinuria. N Engl J Med. 1999;341:1572–1576
  24. Refsum H, Grindflek AW, Ueland PM, Fredriksen A, Meyer K, Ulvik A, et al. Screening for serum total homocysteine in newborn children. Clin Chem. 2004;50:1769–1784
  25. Bowron A, Barton A, Scott J, Stansbie D. Blood spot homocysteine: a feasibility and stability study. Clin Chem. 2005;51:257–258
  26. Linnebank M, Homberger A, Kraus JP, Harms E, Kozich V, Koch HG. Haplotyping of wild-type and I278T alleles of the human cystathionine beta-synthase gene based on a cluster of novel SNPs in IVS12. Hum Mutat. 2001;17:350–351

 Supported by the Wellcome Trust International Senior Research Fellowship in Biomedical Science in Central Europe (reg. No 070255/Z/03/Z). Institutional support was provided by the Research Project of the Ministry of Education of the Czech Republic (reg. No MSM0021620806). The authors declare no conflict of interests.

PII: S0022-3476(08)00779-8

doi: 10.1016/j.jpeds.2008.09.015

The Journal of Pediatrics
Volume 154, Issue 3 , Pages 431-437 , March 2009