title: Spectrum of mutations in the arylsulfatase A gene in a Canadian DNA collection including two novel frameshift mutations, a new missense mutation (C488R) and an MLD mutation (R84Q) in cis with a pseudodeficiency allele.
abstract: We describe three novel mutations in the human arylsulfatase A gene in three patients with MLD, an autosomal recessive lysosomal storage disorder. An insertion, 2590_2591insCCCC in exon 8 and a deletion, 752_758delGCCGGCC, in exon 3 will both result in frameshifts. A mutation in exon 8, 2566T-->C, results in a missense mutation C488R, disrupting an unusual cysteine-knot at the C-terminal end of the protein. All three mutations are heterozygous with previously documented mutations. A previously reported mutation, R84Q was identified on a pseudodeficiency allele. These mutations are part of a heterogeneous spectrum of mutations found in a collection of DNA samples from MLD patients from across Canada and the USA.
authors.affiliation: Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada V6H 3V4. marioncm@interchange.ubc.ca
authors.forename: Marion B
authors.initials: MB
authors.lastname: Coulter-Mackie
authors.forename: Liane
authors.initials: L
authors.lastname: Gagnier
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002170:Canada; D002553:Cerebroside-Sulfatase / Q000172:deficiency* / Q000235:genetics*; D002675:Child, Preschool; D030561:Databases, Nucleic Acid; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007966:Leukodystrophy, Metachromatic / Q000235:genetics*; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D002553:Cerebroside-Sulfatase