title: [Genomic analysis of Japanese patients with adult-type metachromatic leukodystrophy].
abstract: We performed the genomic analysis of arylsulfatase A (ASA) gene in five Japanese patients with adult-type metachromatic leukodystrophy (MLD) including two sibling cases. Sequencing of amino acid coding region of ASA gene of proband case of family A disclosed 426Pro (CCG)-->Leu (CTG) mutation, which was reported to be frequently found in Caucasian patients with late-onset MLD. We developed mismatch primer PCR/RFLP method for detection of this mutation. If 426Pro-->Leu mutation exists in genomic DNA, Pst I site is newly created by PCR with a 3'-primer mismatched at one nucleotide. Genomic analysis of family A members using this method revealed that younger patient was homozygote of 426Pro-->Leu mutation and patient's parents and her younger brother were heterozygotes, which were confirmed by sequencing of exon 8 of ASA gene. Screening of this mutation using mismatch primer PCR/RFLP method was performed in one sibling case and one autopsy case. This point mutation was found in the sibling case. These results showed the possibility of world-wide spread of 426Pro-->Leu mutation in late-onset MLD patients and usefulness of our mismatch primer PCR/RFLP method for screening of this mutation.
authors.affiliation: Division of Inherited Metabolic Disease, Iwate Medical School.
authors.forename: T
authors.initials: T
authors.lastname: Ohshima
authors.forename: J
authors.initials: J
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Tohgi
authors.forename: N
authors.initials: N
authors.lastname: Sakuragawa
mesh_terms: D000328:Adult; D001483:Base Sequence; D002553:Cerebroside-Sulfatase / Q000235:genetics; D005260:Female; D006801:Humans; D007564:Japan; D007966:Leukodystrophy, Metachromatic / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D002553:Cerebroside-Sulfatase