Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/7352
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Type: Journal article
Title: Novel Mutations in Sanfilippo A Syndrome : Implications For Enzyme Function
Author: Weber, B.
Guo, X.
Wraith, J.
Cooper, A.
Kleijer, W.
Bunge, S.
Hopwood, J.
Citation: Human Molecular Genetics, 1997; 6(9):1573-1579
Publisher: OXFORD UNIV PRESS
Issue Date: 1997
ISSN: 0964-6906
1460-2083
Abstract: Sanfilippo syndrome type A or mucopolysaccharidosis IIIA (MPS IIIA) is an autosomal recessive lysosomal storage disorder caused by the deficiency of sulfamidase. The resulting lysosomal storage of heparan sulfate may lead to severe neurodegeneration preceded by progressive dementia, often combined with aggressive and hyperactive behaviour. A total of 109 patients from four different geographic areas were screened for the common mutation R245H and two other previously identified mutations. SSCP analysis of exons was used to characterize the unknown alleles. We identified 16 novel sequence variants, 12 of them likely to be pathogenic. The majority of the pathogenic variants were single base pair changes leading to missense mutations. Several single base pair deletions/insertions and one nonsense mutation were also identified. Altogether, we were able to characterize 55% of the pathogenic alleles. Sequence homology between sulfamidase and N-acetylgalactosamine 4-sulfatase, the first sulfatase to have its tertiary structure defined, suggests that amino acid residues R74 and T79, which were found to be mutated, are likely to be involved in the formation of the active site of sulfamidase. R245H accounts for 31% of the Sanfilippo A alleles in Australasia, for 19.2% of the alleles in patients from the UK and has a high frequency of 57.8% in patients from The Netherlands. The identification of mutations common in certain geographic regions or ethnic groups will help in the diagnosis of MPS IIIA and allow carrier testing and improved genetic counselling.
Keywords: Humans; Mucopolysaccharidosis III; Hydrolases; DNA Primers; Polymerase Chain Reaction; Gene Frequency; Genotype; Phenotype; Point Mutation; Polymorphism, Genetic; Polymorphism, Single-Stranded Conformational; Molecular Sequence Data
RMID: 0030005603
DOI: 10.1093/hmg/6.9.1573
Appears in Collections:Paediatrics publications
Environment Institute Leaders publications

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