title: Metachromatic leucodystrophy: a newly identified mutation in arylsulphatase A, D281Y, found as a compound heterozygote with I179L in an adult onset case.
abstract: The majority of mutations identified in patients with Metachromatic leucodystrophy are unique to individual families. We report here a new mutation in the arylsulphatase A gene (D281Y) identified in a patient with late-onset Metachromatic leucodystrophy. This mutation was inherited in cis with the common pseudo-deficiency allele and in trans with the previously described I179S (250100.0008) mutation which complicated the enzymatic diagnosis of this condition. Sequence comparison shows D281 to be highly conserved amongst the arylsulphatases. The clinical features of this patient which are predominantly of a slowly progressive psychiatric and intellectual deterioration rather than rapid neurological impairment are typical of I179S compound heterozygotes.
authors.affiliation: Department of Clinical Biochemistry, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Halsall
authors.forename: E P
authors.initials: EP
authors.lastname: Halligan
authors.forename: T S
authors.initials: TS
authors.lastname: Elsey
authors.forename: T M
authors.initials: TM
authors.lastname: Cox
mesh_terms: D000328:Adult; D017668:Age of Onset; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002553:Cerebroside-Sulfatase / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000032:analysis; D005260:Female; D006579:Heterozygote; D006801:Humans; D007966:Leukodystrophy, Metachromatic / Q000201:enzymology / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense
chemical_list: D004247:DNA; D002553:Cerebroside-Sulfatase