title: Identification of 16 sulfamidase gene mutations including the common R74C in patients with mucopolysaccharidosis type IIIA (Sanfilippo A).
abstract: 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.
authors.affiliation: Institut für Humangenetik, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Bunge
authors.forename: H
authors.initials: H
authors.lastname: Ince
authors.forename: C
authors.initials: C
authors.lastname: Steglich
authors.forename: W J
authors.initials: WJ
authors.lastname: Kleijer
authors.forename: M
authors.initials: M
authors.lastname: Beck
authors.forename: J
authors.initials: J
authors.lastname: Zaremba
authors.forename: O P
authors.initials: OP
authors.lastname: van Diggelen
authors.forename: B
authors.initials: B
authors.lastname: Weber
authors.forename: J J
authors.initials: JJ
authors.lastname: Hopwood
authors.forename: A
authors.initials: A
authors.lastname: Gal
mesh_terms: D001665:Binding Sites; D002478:Cells, Cultured; D005060:Europe; D005347:Fibroblasts; D005787:Gene Frequency; D005796:Genes; D018740:Genetic Heterogeneity; D006801:Humans; D006867:Hydrolases / Q000235:genetics*; D009084:Mucopolysaccharidosis III / Q000201:enzymology / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009692:Nucleic Acid Heteroduplexes; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D009692:Nucleic Acid Heteroduplexes; D006867:Hydrolases; C022708:N-sulfoglucosamine sulfohydrolase