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

Hum Mutat. 1997;10(6):479-85. doi: 10.1002/(SICI)1098-1004(1997)10:6<479::AID-HUMU10>3.0.CO;2-X.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cells, Cultured
  • Europe
  • Fibroblasts
  • Gene Frequency
  • Genes
  • Genetic Heterogeneity
  • Humans
  • Hydrolases / genetics*
  • Mucopolysaccharidosis III / enzymology
  • Mucopolysaccharidosis III / genetics*
  • Mutation / genetics*
  • Nucleic Acid Heteroduplexes
  • Polymorphism, Single-Stranded Conformational


  • Nucleic Acid Heteroduplexes
  • Hydrolases
  • N-sulfoglucosamine sulfohydrolase