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The molecular basis of Sanfilippo syndrome type B

Zhao, H G; Li, H H; Bach, G; Schmidtchen, Artur LU and Neufeld, E F (1996) In Proceedings of the National Academy of Sciences 93(12). p.6101-6105
Abstract
The Sanfilippo syndrome type B is a lysosomal storage disorder caused by deficiency of alpha-N-acetylglucosaminidase; it is characterized by profound mental deterioration in childhood and death in the second decade. For understanding the molecular genetics of the disease and for future development of DNA-based therapy, we have cloned the cDNA and gene encoding alpha-N-acetylglucosaminidase. Cloning started with purification of the bovine enzyme and use of a conserved oligonucleotide sequence to probe a human cDNA library. The cDNA sequence was found to encode a protein of 743 amino acids, with a 20- to 23-aa signal peptide immediately preceding the amino terminus of the tissue enzyme and with six potential N-glycosylation sites. The 8.5-kb... (More)
The Sanfilippo syndrome type B is a lysosomal storage disorder caused by deficiency of alpha-N-acetylglucosaminidase; it is characterized by profound mental deterioration in childhood and death in the second decade. For understanding the molecular genetics of the disease and for future development of DNA-based therapy, we have cloned the cDNA and gene encoding alpha-N-acetylglucosaminidase. Cloning started with purification of the bovine enzyme and use of a conserved oligonucleotide sequence to probe a human cDNA library. The cDNA sequence was found to encode a protein of 743 amino acids, with a 20- to 23-aa signal peptide immediately preceding the amino terminus of the tissue enzyme and with six potential N-glycosylation sites. The 8.5-kb gene (NAGLU), interrupted by 5 introns, was localized to the 5'-flanking sequence of a known gene, EDH17B, on chromosome 17q21. Five mutations were identified in cells of patients with Sanfilippo syndrome type B: 503del10, R297X, R626X, R643H, and R674H. The occurrence of a frameshift and a nonsense mutation in homozygous form confirms the identity of the NAGLU gene. (Less)
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author
publishing date
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Contribution to journal
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published
subject
in
Proceedings of the National Academy of Sciences
volume
93
issue
12
pages
6101 - 6105
publisher
National Acad Sciences
external identifiers
  • pmid:8650226
  • scopus:15844423859
ISSN
1091-6490
language
English
LU publication?
no
id
d54bcc75-d70f-4664-ac6e-f604d162e1d4 (old id 1110817)
alternative location
http://www.pnas.org/content/93/12/6101.full.pdf+html
date added to LUP
2008-07-30 10:34:07
date last changed
2017-10-08 03:32:53
@article{d54bcc75-d70f-4664-ac6e-f604d162e1d4,
  abstract     = {The Sanfilippo syndrome type B is a lysosomal storage disorder caused by deficiency of alpha-N-acetylglucosaminidase; it is characterized by profound mental deterioration in childhood and death in the second decade. For understanding the molecular genetics of the disease and for future development of DNA-based therapy, we have cloned the cDNA and gene encoding alpha-N-acetylglucosaminidase. Cloning started with purification of the bovine enzyme and use of a conserved oligonucleotide sequence to probe a human cDNA library. The cDNA sequence was found to encode a protein of 743 amino acids, with a 20- to 23-aa signal peptide immediately preceding the amino terminus of the tissue enzyme and with six potential N-glycosylation sites. The 8.5-kb gene (NAGLU), interrupted by 5 introns, was localized to the 5'-flanking sequence of a known gene, EDH17B, on chromosome 17q21. Five mutations were identified in cells of patients with Sanfilippo syndrome type B: 503del10, R297X, R626X, R643H, and R674H. The occurrence of a frameshift and a nonsense mutation in homozygous form confirms the identity of the NAGLU gene.},
  author       = {Zhao, H G and Li, H H and Bach, G and Schmidtchen, Artur and Neufeld, E F},
  issn         = {1091-6490},
  language     = {eng},
  number       = {12},
  pages        = {6101--6105},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {The molecular basis of Sanfilippo syndrome type B},
  volume       = {93},
  year         = {1996},
}