Identification of a nonsense mutation in ALD protein cDNA from a patient with adrenoleukodystrophy

Biochem Biophys Res Commun. 1994 Jan 28;198(2):632-6. doi: 10.1006/bbrc.1994.1092.


The molecular basis of X-linked adrenoleukodystrophy (ALD) was investigated. Six (A to 50) fragments of cDNA for ALD protein (Mosser et al. Nature 361: 726-730, 1993) from an adult patient with adrenomyeloneuropathy were amplified by PCR and mutations were screened by Mutation Detection Enhancement gel electrophoresis. A single base substitution (2154 C-->T, which resulted in the formation of a termination codon for glutamine (Q590STOP) and deletes Pst I site (CTGCAG-->CTGTAG), was detected. Eight other ALD patients did not have this mutation. A family study revealed the presence of both the mutant and normal alleles in the mother, a sister and a niece, indicating that these individuals were carriers. A nephew with childhood ALD who died 10 years earlier had the same mutant allele as detected by Pst I restriction assay. This report is the first description of a mutant allele for ALD, at the cDNA level, and presents confirmatory evidence of ALD protein as the primary etiology of ALD.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters*
  • Adrenoleukodystrophy / genetics*
  • Adult
  • Alleles
  • Asian People / genetics
  • Base Sequence
  • Carrier Proteins / genetics*
  • Child
  • DNA, Complementary / genetics*
  • Deoxyribonucleases, Type II Site-Specific / metabolism
  • Exons / genetics
  • Female
  • Genetic Linkage
  • Glutamine / genetics
  • Humans
  • Japan
  • Male
  • Membrane Proteins / genetics*
  • Molecular Sequence Data
  • Nucleic Acid Heteroduplexes / genetics
  • Pedigree
  • Point Mutation*
  • Sequence Deletion
  • Terminator Regions, Genetic / genetics
  • X Chromosome


  • ABCD1 protein, human
  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters
  • Carrier Proteins
  • DNA, Complementary
  • Membrane Proteins
  • Nucleic Acid Heteroduplexes
  • Glutamine
  • CTGCAG-specific type II deoxyribonucleases
  • Deoxyribonucleases, Type II Site-Specific