Identification of Mutations in the Putative ATP-binding Domain of the Adrenoleukodystrophy Gene

J Clin Invest. 1994 Aug;94(2):516-20. doi: 10.1172/JCI117363.

Abstract

The recently identified adrenoleukodystrophy (ALD) gene is predicted to encode a peroxisomal protein of 745 amino acids that includes one domain for ATP-binding, termed nucleotide-binding fold (NBF). To determine whether mutations occur in the putative NBF of ALD protein, we analyzed by denaturing gradient gel electrophoresis (DGGE) exon 6 and 8 that encode most part of this domain in 50 ALD patients. Four amino acid substitutions, three frameshift mutations leading to premature termination signal, and a splicing mutation were identified. These amino acid substitutions occurred at residues highly conserved in other ATP-binding cassette (ABC) proteins. In addition, a nonsense mutation was detected in exon 4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters*
  • Adenosine Triphosphate / metabolism*
  • Adrenoleukodystrophy / genetics*
  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • Carrier Proteins / genetics*
  • Exons
  • Humans
  • Membrane Proteins / genetics*
  • Molecular Sequence Data
  • Mutation*

Substances

  • ABCD1 protein, human
  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters
  • Carrier Proteins
  • Membrane Proteins
  • Adenosine Triphosphate