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NAGLU mutations underlying Sanfilippo syndrome type B

Schmidtchen, Artur LU ; Greenberg, D; Zhao, H G; Li, H H; Huang, Y; Tieu, P; Zhao, H Z; Cheng, S; Zhao, Z and Whitley, C B, et al. (1998) In American Journal of Human Genetics 62(1). p.64-69
Abstract
Sanfilippo syndrome type B (mucopolysaccharidosis III B) is a rare autosomal recessive disease caused by deficiency of alpha-N-acetylglucosaminidase, one of the enzymes required for the lysosomal degradation of heparan sulfate. The gene for this enzyme, NAGLU, recently was isolated, and several mutations were characterized. We have identified, in amplified exons from nine fibroblast cell lines derived from Sanfilippo syndrome type B patients, 10 additional mutations: Y92H, P115S, Y140C, E153K, R203X, 650insC, 901delAA, P358L, A664V, and L682R. Four of these mutations were found in homozygosity, and only two were seen in more than one cell line. Thus, Sanfilippo syndrome type B shows extensive molecular heterogeneity. Stable transfection of... (More)
Sanfilippo syndrome type B (mucopolysaccharidosis III B) is a rare autosomal recessive disease caused by deficiency of alpha-N-acetylglucosaminidase, one of the enzymes required for the lysosomal degradation of heparan sulfate. The gene for this enzyme, NAGLU, recently was isolated, and several mutations were characterized. We have identified, in amplified exons from nine fibroblast cell lines derived from Sanfilippo syndrome type B patients, 10 additional mutations: Y92H, P115S, Y140C, E153K, R203X, 650insC, 901delAA, P358L, A664V, and L682R. Four of these mutations were found in homozygosity, and only two were seen in more than one cell line. Thus, Sanfilippo syndrome type B shows extensive molecular heterogeneity. Stable transfection of Chinese hamster ovary cells, by cDNA mutagenized to correspond to the NAGLU missense mutations, did not yield active enzyme, demonstrating the deleterious nature of the mutations. Nine of the 10 amino acid substitutions identified to date are clustered near the amino or the carboxyl end of alpha-N-acetylglucosaminidase, suggesting a role for these regions in the transport or function of the enzyme. (Less)
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type
Contribution to journal
publication status
published
subject
keywords
Sanfilippos syndrome, Mucopolysaccharidosis III, greek small letter alpha-N-acetylglucosaminidase, Lysosomal storage disease, NAGLUmutations
in
American Journal of Human Genetics
volume
62
issue
1
pages
64 - 69
publisher
Cell Press
external identifiers
  • pmid:9443878
  • scopus:17344367091
ISSN
0002-9297
DOI
10.1086/301685
language
English
LU publication?
no
id
e6399990-ba26-420c-aad0-af623142f560 (old id 1113622)
date added to LUP
2008-07-16 09:04:36
date last changed
2017-09-17 05:31:18
@article{e6399990-ba26-420c-aad0-af623142f560,
  abstract     = {Sanfilippo syndrome type B (mucopolysaccharidosis III B) is a rare autosomal recessive disease caused by deficiency of alpha-N-acetylglucosaminidase, one of the enzymes required for the lysosomal degradation of heparan sulfate. The gene for this enzyme, NAGLU, recently was isolated, and several mutations were characterized. We have identified, in amplified exons from nine fibroblast cell lines derived from Sanfilippo syndrome type B patients, 10 additional mutations: Y92H, P115S, Y140C, E153K, R203X, 650insC, 901delAA, P358L, A664V, and L682R. Four of these mutations were found in homozygosity, and only two were seen in more than one cell line. Thus, Sanfilippo syndrome type B shows extensive molecular heterogeneity. Stable transfection of Chinese hamster ovary cells, by cDNA mutagenized to correspond to the NAGLU missense mutations, did not yield active enzyme, demonstrating the deleterious nature of the mutations. Nine of the 10 amino acid substitutions identified to date are clustered near the amino or the carboxyl end of alpha-N-acetylglucosaminidase, suggesting a role for these regions in the transport or function of the enzyme.},
  author       = {Schmidtchen, Artur and Greenberg, D and Zhao, H G and Li, H H and Huang, Y and Tieu, P and Zhao, H Z and Cheng, S and Zhao, Z and Whitley, C B and Di Natale, P and Neufeld, E F},
  issn         = {0002-9297},
  keyword      = {Sanfilippos syndrome,Mucopolysaccharidosis III,greek small letter alpha-N-acetylglucosaminidase,Lysosomal storage disease,NAGLUmutations},
  language     = {eng},
  number       = {1},
  pages        = {64--69},
  publisher    = {Cell Press},
  series       = {American Journal of Human Genetics},
  title        = {NAGLU mutations underlying Sanfilippo syndrome type B},
  url          = {http://dx.doi.org/10.1086/301685},
  volume       = {62},
  year         = {1998},
}