title: A D255H substitution in the arylsulphatase A gene of two unrelated Belgian patients with late-infantile metachromatic leukodystrophy.
abstract: Metachromatic leukodystrophy (MLD) is an autosomal recessive disease of myelin metabolism caused by a deficiency in the lysosomal enzyme arylsulphatase A (ARSA). We have identified a new mutation in exon 4 of the ARSA gene of two unrelated Belgian patients with late-infantile MLD. The mutation predicts an aspartic acid-to-histidine substitution at position 255 in arylsulphatase A (D255H), in a highly conserved region among sulphatases. Transient expression of the mutation in COS cells did not show an increase in ARSA activity. Both patients were compound heterozygotes carrying the frequent splice site mutation in intron 2 (459 + IG -->A) on the other allele.
authors.affiliation: Department of Medical Genetics, University Hospitals, Brussels, Belgium.
authors.forename: W
authors.initials: W
authors.lastname: Lissens
authors.forename: R
authors.initials: R
authors.lastname: Vervoort
authors.forename: N
authors.initials: N
authors.lastname: Van Regemorter
authors.forename: P
authors.initials: P
authors.lastname: Van Bogaert
authors.forename: M
authors.initials: M
authors.lastname: Freund
authors.forename: C
authors.initials: C
authors.lastname: Verellen-Dumoulin
authors.forename: S
authors.initials: S
authors.lastname: Seneca
authors.forename: I
authors.initials: I
authors.lastname: Liebaers
mesh_terms: D000818:Animals; D019556:COS Cells; D002553:Cerebroside-Sulfatase / Q000235:genetics*; D006801:Humans; D007966:Leukodystrophy, Metachromatic / Q000235:genetics*; D008297:Male; D009154:Mutation
chemical_list: D002553:Cerebroside-Sulfatase