Eight Novel ABCD1 Gene Mutations and Three Polymorphisms in Patients With X-linked Adrenoleukodystrophy: The First Polymorphism Causing an Amino Acid Exchange

Hum Mutat. 2001;18(1):52-60. doi: 10.1002/humu.1149.


X-ALD is a neurological disorder associated with inherited defects in the ABCD1 (ALD) gene located on Xq28 and with impaired peroxisomal very long-chain fatty acid beta-oxidation. We examined the ABCD1 gene in probands from 11 unrelated X-ALD Czech and Slovak families by the direct sequencing of cDNA or genomic PCR products. In 10 families there were 10 different mutations, eight of which were novel. The spectrum of mutations consists of six point mutations, three microdeletions (1bp, 2bp, 4 bp), and one large deletion (229bp). In the 11th family we detected two novel single-base pair substitutions in exon 1 (c.38 A>C and c.649 A>G), both causing amino acid exchanges (N13T and K217E). Expression studies revealed that only K217E is a deleterious mutation, because a plasmid encoding ALDP with K217E was ineffective in the restoration of defective beta-oxidation in X-ALD fibroblasts. The N13T amino acid exchange, on the other hand, did not affect ALDP function. Thus, N13T represents the first polymorphism causing an amino acid exchange in the ABCD1 gene. As this polymorphism was observed neither in 100 control alleles nor in 300 X-ALD patients who have been sequenced so far world-wide, it seems to be very rare or unique. Two additional novel polymorphisms were found by the sequencing of the ABCD1 gene from our patients: c.-59 C/T in the 5'untranslated region and c.2019 C/T (F673F) in exon 10. The frequencies of these two polymorphisms, were 11/150 and 2/150 control alleles, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics
  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters / chemistry
  • ATP-Binding Cassette Transporters / genetics*
  • Adolescent
  • Adrenoleukodystrophy / genetics*
  • Adult
  • Alleles
  • Amino Acid Motifs
  • Child
  • Conserved Sequence
  • Czech Republic
  • DNA Mutational Analysis
  • Exons / genetics
  • Fatty Acids / metabolism
  • Female
  • Genetic Linkage / genetics*
  • Humans
  • Male
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Molecular Sequence Data
  • Mutation, Missense / genetics*
  • Oxidation-Reduction
  • Palmitic Acid / metabolism
  • Phenotype
  • Polymorphism, Genetic / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Slovakia
  • X Chromosome / genetics*


  • 5' Untranslated Regions
  • ABCD1 protein, human
  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters
  • Fatty Acids
  • Membrane Proteins
  • Palmitic Acid
  • lignoceric acid

Associated data

  • GENBANK/U52111