Splicing error due to a splice acceptor site mutation in the ALD gene identified in a Japanese childhood cerebral adrenoleukodystrophy case

Kobe J Med Sci. 1998 Feb;44(1):9-17.

Abstract

X-linked adrenoleukodystrophy (ALD) is characterised by progressive multifocal demyelination of central nervous system and adrenocortical insufficiency. This disorder has been also associated with mutations in the ALD gene, encoding an ATP-binding transporter which is located in the peroxisomal membrane. Defect of the gene may lead to impaired peroxisomal beta-oxidation and increase of serum and tissue very long chain fatty acids (VLCFAs). Here we report the results of analysis of the ALD gene in a Japanese patient with childhood cerebral ALD. In our patient, by sequencing of the ALD cDNA, an 8 bp insertion (ACCCCCAG) was detected at the start of exon 9, which corresponded to nucleotides from position -1 to -8 of the 3' splice acceptor site of intron 8. Sequencing of genomic DNA showed a single nucleotide substitution at position-10 of the 3' splice acceptor site of intron 8 replacing a G with an A which activated a cryptic splice acceptor site. It is concluded that a splicing error was induced by a point mutation that created a novel splice acceptor site. This insertion created a nonsense codon downstream, producing a truncated ALD protein. His mother and younger sister with increased VLCFA ratios were heterozygotes of normal and mutant ALD genes.

Publication types

  • Case Reports

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Adrenoleukodystrophy / diagnosis
  • Adrenoleukodystrophy / genetics*
  • Base Sequence
  • Child
  • DNA Primers / analysis
  • Gene Expression*
  • Humans
  • Male
  • Molecular Sequence Data
  • Pedigree
  • Point Mutation*
  • Polymerase Chain Reaction

Substances

  • ATP-Binding Cassette Transporters
  • DNA Primers