PMID- 10094189
OWN - NLM
STAT- MEDLINE
DCOM- 19990513
LR  - 20071115
IS  - 1018-4813 (Print)
IS  - 1018-4813 (Linking)
VI  - 7
IP  - 1
DP  - 1999 Jan
TI  - Sanfilippo type B syndrome (mucopolysaccharidosis III B): allelic heterogeneity
      corresponds to the wide spectrum of clinical phenotypes.
PG  - 34-44
AB  - Sanfilippo B syndrome (mucopolysaccharidosis IIIB, MPS IIIB) is caused by a
      deficiency of alpha-N-acetylglucosaminidase, a lysosomal enzyme involved in the
      degradation of heparan sulphate. Accumulation of the substrate in lysosomes leads
      to degeneration of the central nervous system with progressive dementia often
      combined with hyperactivity and aggressive behaviour. Age of onset and rate of
      progression vary considerably, whilst diagnosis is often delayed due to the
      absence of the pronounced skeletal changes observed in other
      mucopolysaccharidoses. Cloning of the gene and cDNA encoding
      alpha-N-acetylglucosaminidase enabled a study of the molecular basis of this
      syndrome. We were able to identify 31 mutations, 25 of them novel, and two
      polymorphisms in the 40 patients mostly of Australasian and Dutch origin included
      in this study. The observed allellic heterogeneity reflects the wide spectrum of 
      clinical phenotypes reported for MPS IIIB patients. The majority of changes are
      missense mutations; also four nonsense and nine frameshift mutations caused by
      insertions or deletions were identified. Only five mutations were found in more
      than one patient and the observed frequencies are well below those observed for
      the common mutations in MPS IIIA. R643C and R297X each account for around 20% of 
      MPS IIIB alleles in the Dutch patient group, whilst R297X, P521L, R565W and R626X
      each have a frequency of about 6% in Australasian patients. R643C seems to be a
      Dutch MPS IIIB allele and clearly confers the attenuated phenotype. One region of
      the gene shows a higher concentration of mutations, probably reflecting the
      instability of this area which contains a direct repeat. Several arginine
      residues seem to be 'hot-spots' for mutations, being affected by two or three
      individual base pair exchanges.
FAU - Weber, B
AU  - Weber B
AD  - Department of Chemical Pathology, Women's and Children's Hospital, North
      Adelaide, Australia.
FAU - Guo, X H
AU  - Guo XH
FAU - Kleijer, W J
AU  - Kleijer WJ
FAU - van de Kamp, J J
AU  - van de Kamp JJ
FAU - Poorthuis, B J
AU  - Poorthuis BJ
FAU - Hopwood, J J
AU  - Hopwood JJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Hum Genet
JT  - European journal of human genetics : EJHG
JID - 9302235
RN  - 0 (DNA Primers)
RN  - EC 3.2.1.50 (alpha-N-acetyl-D-glucosaminidase)
RN  - EC 3.2.1.52 (Acetylglucosaminidase)
SB  - IM
MH  - Acetylglucosaminidase/genetics
MH  - *Alleles
MH  - Base Sequence
MH  - DNA Primers
MH  - *Genetic Heterogeneity
MH  - Genotype
MH  - Humans
MH  - Mucopolysaccharidosis III/*genetics
MH  - Mutation
MH  - Phenotype
EDAT- 1999/03/27 00:00
MHDA- 1999/03/27 00:01
CRDT- 1999/03/27 00:00
PHST- 1999/03/27 00:00 [pubmed]
PHST- 1999/03/27 00:01 [medline]
PHST- 1999/03/27 00:00 [entrez]
AID - 10.1038/sj.ejhg.5200242 [doi]
PST - ppublish
SO  - Eur J Hum Genet. 1999 Jan;7(1):34-44. doi: 10.1038/sj.ejhg.5200242.