Identification of 16 sulfamidase gene mutations including the common R74C in patients with mucopolysaccharidosis type IIIA (Sanfilippo A)

Susanna Bunge, Hüscyin Ince, Cordula Steglich, Wim J. Kleijer, Michael Beck, Jacek Zaremba, Otto P. Van Diggelen, Birgit Weber, John J. Hopwood, Andreas Gal

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Mucopolysaccharidosis type IIIA (MPS IIIA or Sanfilippo A disease) is a storage disorder caused by deficiency of the lysosomal enzyme sulfamidase. Mutation screening, using SSCP/heteroduplex analyses on cDNA and genomic DNA fragments, was performed in a group of 42 European patients. Sixteen of the 17 different gene mutations characterized have not been previously described. The spectrum of gene lesions consists of two 1-bp deletions (1091delC, 1093delG), an 18-bp duplication (421ins18), a splice site mutation (IVS2- 2A→G), and 13 different missense point mutations. As in other lysosomal storage disorders, the phenotypic heterogeneity is associated with a considerable genetic heterogeneity. The missense mutation R74C, which alters an evolutionary conserved amino acid in the active site of the enzyme, was found on 56% of alleles of 16 Polish patients, whereas it was less frequent among German patients (21% of disease alleles). R245H, a previously reported common mutation, represents 35% of disease alleles in German patients, but only 3% in Polish patients. As the combined frequency of the common mutations (R74C and R245H) in German and Polish populations exceeds 55%, screening for these two mutations will assist molecular genetic diagnosis of MPS IIIA and allow heterozygote testing in these populations.

Original languageEnglish
Pages (from-to)479-485
Number of pages7
JournalHuman mutation
Issue number6
Publication statusPublished or Issued - 1997


  • Common mutations
  • Mucopolysaccharidosis type IIIA
  • Mutation screening
  • Sanfilippo A disease
  • Sulfamidase

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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