Abstract
Sanfilippo type B syndrome (mucopolysaccharidosis type IIIB; MPS IIIB) is an autosomal recessive lysosomal storage disorder that is caused by defective α- N-acetylglucosaminidase (NAGLU). We performed NAGLU gene analysis in five patients with MPS IIIB whose respective parents from the Okinawa islands in Japan were not apparently consanguineous. We found a missense mutation (R565P) in all five patients (all homozygotes). We screened this mutation in 200 healthy subjects and found one heterozygote (none of the subjects were related to the patients). These results suggest that there may be a founder effect that results in the accumulation of R565P mutation in this area.
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Beesley CE, Young EP, Vellodi A, Winchester BG (1998) Identification of 12 novel mutations in the alpha- N-acetylglucosaminidase gene in 14 patients with Sanfilippo syndrome type B (mucopolysaccharidosis type IIIB). J Med Genet 35:910–914
Bunge S, Knigge A, Steglich C, Kleijer WJ, van Diggelen OP, Beck M, Gal A (1999) Mucopolysaccharidosis type IIIB (Sanfilippo B): identification of 18 novel alpha- N-acetylglucosaminidase gene mutations. J Med Genet 36:28–31
Hall CW, Liebaers I, Di Natale P, Neufeld EF (1978) Enzymic diagnosis of the genetic mucopolysaccharide storage disorders. Methods Enzymol 50:439–56
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
Meikle PJ, Hopwood JJ, Clague AE, Carey WF (1999) Prevalence of lysosomal storage disorders. JAMA 281:249–254
Nelson J (1997) Incidence of the mucopolysaccharidoses in Northern Ireland. Hum Genet 101:355–358
Nelson DL, Cox MM (2000) Lehninger principles of biochemistry, 3rd edn. Worth, NY, pp 120–168
Schmidtchen A, Greenberg D, Zhao HG, Li HH, Huang Y, Tieu P, Zhao HZ, Cheng S, Zhao Z, Whitley CB, Di Natale P, Neufeld EF (1998) NAGLU mutations underlying Sanfilippo syndrome type B. Am J Hum Genet 62:64–69
Tanaka A, Kimura M, Lan HTN, Takaura N, Yamano T (2002) Molecular analysis of the ?-N-acetylglucosaminidase gene in seven Japanese patients from six unrelated families with mucopolysaccharidosis IIIB (Sanfilippo type B), including two novel mutations. J Hum Genet 47:484–487
Tessitore A, Villani GR, Di Domenico C, Filocamo M, Gatti R, Di Natale P (2000) Molecular defects in the alpha- N-acetylglucosaminidase gene in Italian Sanfilippo type B patients. Hum Genet 107:568–576
Vogel F, Motulsky AG (1997) Human genetics; problems and approaches, 3rd edn. Springer, Berlin Heidelberg New York, pp 413–415
Weber B, Blanch L, Clements PR, Scott HS, Hopwood JJ (1996) Cloning and expression of the gene involved in Sanfilippo B syndrome (mucopolysaccharidosis III B). Hum Mol Genet 5:771–777
Weber B, Guo XH, Kleijer WJ, van de Kamp JJ, Poorthuis BJ, Hopwood JJ (1999) Sanfilippo type B syndrome (mucopolysaccharidosis III B): allelic heterogeneity corresponds to the wide spectrum of clinical phenotypes. Eur J Hum Genet 7:34–44
Zhao HG, Li HH, Bach G, Schmidtchen A, Neufeld EF (1996) The molecular basis of Sanfilippo syndrome type B. Proc Natl Acad Sci USA 93:6101–6105
Zhao HG, Aronovich EL, Whitley CB (1998) Genotype–phenotype correspondence in Sanfilippo syndrome type B. Am J Hum Genet 62:53–63
Acknowledgements
We thank Dr. K. Hayasaka (Gifu University School of Medicine) for their contribution to the assay of NAGLU activities in fibroblasts.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chinen, Y., Tohma, T., Izumikawa, Y. et al. Sanfilippo type B syndrome: five patients with an R565P homozygous mutation in the α-N-acetylglucosaminidase gene from the Okinawa islands in Japan. J Hum Genet 50, 357–359 (2005). https://doi.org/10.1007/s10038-005-0258-4
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1007/s10038-005-0258-4
Keywords
This article is cited by
-
Epidemiology of mucopolysaccharidoses (MPS) in United States: challenges and opportunities
Orphanet Journal of Rare Diseases (2021)
-
Residual N‐acetyl‐α‐glucosaminidase activity in fibroblasts correlates with disease severity in patients with mucopolysaccharidosis type IIIB
Journal of Inherited Metabolic Disease (2016)
-
“Genotype-first” approaches on a curious case of idiopathic progressive cognitive decline
BMC Medical Genomics (2014)
-
Mucopolysaccharidosis type IIIB may predominantly present with an attenuated clinical phenotype
Journal of Inherited Metabolic Disease (2010)
