Abstract
We have identified a common mutation (R245H) in the sulphamidase gene of Sanfilippo syndrome type A (mucopolysaccharidosis type IIIA, MPS IIIA) patients from The Netherlands. Allele-specific oligonucleotide hybridization was used to determine the incidence of this mutation in 45 unrelated MPS IIIA patients from different regions of The Netherlands. R245H was present in 51 alleles, representing 56.7% of the total allelic population. Of 39 patients, for whom we have uniform clinical details, 13 MPS IIIA patients who were homozygous for this common mutation had a more uniform but severe clinical phenotype than the remaining 21 or 5 patients, containing respectively one or no R245H alleles. The R245H allele had a higher prevalence in western rather than eastern regions of The Netherlands.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Beratis NG, Sklower SL, Wilbur L, Matalon R (1986) Sanfilippo disease in Greece. Clin Genet 29: 129-132.
Blanch L, Weber B, Guo X-H, Scott HS, Hopwood JJ (1997) Molecular defects in Sanfillipo syndrome type A. Hum Mol Genet 6: 787-791.
Bond CS, Clements PR, Ashby SJ, et al (1997) Structure of a human lysosomal sulfatase. Structure 5: 277-289.
Bunge S, Ince H, Steglich C, et al (1997) Identification of 15 sulfamidase gene mutations including the common R74C in patients with mucopolysaccharidosis type IIIA (Sanfilippo A). Hum Mutat 10: 479-485.
Di Natale P, Balzano N, Esposito S, Villani GRD (1997) Identification of molecular defects in Italian Sanfilippo A patients. Hum Mutat, in press.
Karageorgos LE, Guo X-H, Blanch L, et al (1996) Structure and sequence of the human sulphamidase gene. DNA Res 3: 269-271.
Karpova EA, Voznyi YA, Keulemans JLM, et al (1996) A fluorimetric enzyme assay for the diagnosis of Sanfilippo disease type A (MPS IIIA). J Inher Metab Dis 19: 278-285.
Kleijer WJ, Karpova EA, Geilen GC, et al (1996) Prenatal diagnosis of Sanfilippo A syndrome: experience in 35 pregnancies at risk and the use of a new fluorogenic substrate for the heparin sulphamidase assay. Prenat Diagn 16: 829-835.
Lowry RB, Applegarth DA, Toone JR, MacDonald E, Thunem NY (1990) An update on the frequency of mucopolysaccharide syndromes in British Columbia. Hum Genet 85: 389-390.
Michelakakis H, Dimitriou E, Tsagaraki S, Giouroukos S, Schulpis K, Bartsocas CS (1995) Lysosomal storage diseases in Greece. Genet Couns 6: 43-47.
Neufeld EF, Muenzer J (1995) The mucopolysaccharidoses. In Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease, 7th edn. New York: McGraw-Hill, 2465-2494.
Robertson DA, Freeman C, Nelson PV, Morris CP, Hopwood JJ (1988) Human glucosamine 6-sulphatase cDNA reveals homology with steroid sulphatase. Biochem Biophys Res Commun 157: 218-224.
Robertson DA, Freeman C, Morris CP, Hopwood JJ (1992) A cDNA clone for glucosamine-6-sulphatase reveals differences between aryl-and non-aryl sulphatases. Biochem J 288: 539-544.
Scott HS, Litjens T, Nelson PV, Brooks DA, Hopwood JJ, Morris CP (1992) α-L-Iduronidase mutations (Q70X and P533R) associated with a severe Hurler phenotype. Hum Mutat 1: 333-339.
Scott HS, Blanch L, Guo X-H, et al (1995) Cloning of the sulphamidase gene and identification of mutations in Sanfilippo A syndrome. Nature Genetics 11: 465-467.
van de Kamp JJP (1979) The Sanfilippo syndrome: a clinical and genetical study of 75 patients in The Netherlands. Doctoral Thesis. S'Gravenhage: J. H. Pasmans.
van de Kamp JJP, Niermeijer MF, von Figura K, Giesberts MAH (1981) Genetic heterogeneity and clinical variability in the Sanfilippo syndrome (types A, B and C). Clin Genet 20: 152-160.
Weber B, Blanch L, Clements PR, Scott HS, Hopwood JJ (1996) Cloning and expression of the gene involved in Sanfilippo B syndrome (mucopolysaccharidosis IIIB). Hum Mol Genet 5: 771-777.
Weber B, Guo X-H, Wraith JE, et al (1997) Novel mutations in Sanfilippo A syndrome: implications for enzyme function. Hum Mol Genet 6: 1573-1579.
Whiteman P, Young E (1977) The laboratory diagnosis of Sanfilippo disease. Clin Chim Acta 76: 139-147.
Zhao HG, Li HH, Bach G, Schmidtchen A, Neufeld EF (1996) The molecular basis of San-filippo syndrome type B. Proc Natl Acad Sci USA 93: 6101-6105.
Rights and permissions
About this article
Cite this article
Weber, B., van de Kamp, J.J.P., Kleijer, W.J. et al. Identification of a common mutation (R245H) in Sanfilippo A patients from the Netherlands. J Inherit Metab Dis 21, 416–422 (1998). https://doi.org/10.1023/A:1005362826552
Issue Date:
DOI: https://doi.org/10.1023/A:1005362826552