title: Molecular genetic characterization of two metachromatic leukodystrophy patients who carry the T799G mutation and show different phenotypes; description of a novel null-type mutation.
abstract: Metachromatic leukodystrophy (MLD) is an autosomal recessive storage disease caused by deficiency of the lysosomal enzyme, arylsulfatase A. Two common mutations causing MLD have been characterized and correlations between phenotype and genotype have been established. A third common mutation, T799G, has also been identified in European MLD patients, and is associated with the late-onset forms of the disease. We report the molecular analysis of two Italian MLD patients, with juvenile and adult onset of the disease, respectively, who carried the T799G mutation in compound heterozygosity with different null mutations. A novel rapid mutation detection method is demonstrated for patient screening. One patient has a novel mutation, a T553C [corrected] transition that results in the substitution of Pro for Leu at codon 135, and produces no enzymatic activity in transfection experiments.
authors.affiliation: Istituto di Biologia e Genetica, Università di Verona, Italy. macarena@borgoroma.univr.it
authors.forename: M
authors.initials: M
authors.lastname: Gomez-Lira
authors.forename: C
authors.initials: C
authors.lastname: Perusi
authors.forename: M
authors.initials: M
authors.lastname: Mottes
authors.forename: P F
authors.initials: PF
authors.lastname: Pignatti
authors.forename: M
authors.initials: M
authors.lastname: Manfredi
authors.forename: N
authors.initials: N
authors.lastname: Rizzuto
authors.forename: A
authors.initials: A
authors.lastname: Salviati
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D002553:Cerebroside-Sulfatase / Q000235:genetics; D002648:Child; D006224:Cricetinae; D005260:Female; D005347:Fibroblasts; D006579:Heterozygote; D006801:Humans; D007966:Leukodystrophy, Metachromatic / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D009154:Mutation; D010641:Phenotype
chemical_list: D002553:Cerebroside-Sulfatase