Single exon mutation in arylsulfatase A gene has two effects: loss of enzyme activity and aberrant splicing

✍ Scribed by Yoriyasu Hasegawa; Hiroshi Kawame; Hiroyuki Ida; Toya Ohashi; Yoshikatsu Eto

• Publisher: Springer
• Year: 1994
• Tongue: English
• Weight: 955 KB
• Volume: 93
• Category: Article
• ISSN: 0340-6717
• DOI: 10.1007/bf00201666

✦ Synopsis

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 aberranfly. 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.