title: Single exon mutation in arylsulfatase A gene has two effects: loss of enzyme activity and aberrant splicing.
abstract: The arylsulfatase A gene of a Japanese patient who has the juvenile form of metachromatic leukodystrophy, and who has been previously reported as a heterozygote of the 1070A mutation, was investigated. Nucleotide sequence analysis revealed the presence of a previously unreported C-to-T substitution (designated 2330T), 22 nucleotides downstream from the exon 8 splice acceptor site. Although the 2330T mutation itself results in a single amino acid substitution of Thr409 by Ile, the analysis of the patient's cDNA fragments amplified by the reverse transcription-polymerase chain reaction revealed that transcripts of the 2330T allele were spliced both normally and aberrantly. The aberrant splicing produced a 27-nucleotide deletion from the usual exon 8 splice acceptor site. These results indicate that the new mutation is a rare case of an exon mutation affecting splice site selection. The mechanism of this aberrant pre-mRNA splicing is discussed.
authors.affiliation: Department of Pediatrics, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: H
authors.initials: H
authors.lastname: Kawame
authors.forename: H
authors.initials: H
authors.lastname: Ida
authors.forename: T
authors.initials: T
authors.lastname: Ohashi
authors.forename: Y
authors.initials: Y
authors.lastname: Eto
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D002460:Cell Line; D002553:Cerebroside-Sulfatase / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary; D005091:Exons; D006579:Heterozygote; D006801:Humans; D007966:Leukodystrophy, Metachromatic / Q000201:enzymology / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D012322:RNA Precursors / Q000737:chemistry; D012326:RNA Splicing; D012333:RNA, Messenger / Q000737:chemistry
chemical_list: D018076:DNA, Complementary; D012322:RNA Precursors; D012333:RNA, Messenger; D002553:Cerebroside-Sulfatase