Characterisation of two mutations in the ABCD1 gene leading to low levels of normal ALDP

Hum Genet. 2001 Dec;109(6):616-22. doi: 10.1007/s00439-001-0632-z. Epub 2001 Oct 26.


A variety of mutations have been identified in the X-linked adrenoleukodystrophy (X-ALD) gene, none of which is prevalent. In this work we describe a reverse transcription polymerase chain reaction (RT-PCR)-based strategy specially suited to the molecular characterisation of mutations in index cases. After RT-PCR amplification of the X-ALD transcript a conformation-sensitive gel electrophoresis analysis is performed followed by sequencing of the fragments with altered mobility. Two X-ALD patients were studied using this strategy. In both cases, splice site mutations were found. The first patient studied has a single base substitution at the first position of the invariant GT dinucleotide donor splice site of intron 8. In spite of this alteration, small quantities of correctly spliced mRNA molecules were easily detected. In agreement with these data, a small amount of ALDP was found by western blotting analysis. An alteration at the -1 position of the donor splice site of exon 1 was detected in the second patient. This mutation results in the utilisation of a cryptic 5' splice site within intron 1. Nevertheless, this transition also allows for some correct splicing. Western blotting analysis revealed the existence of normal-migrating ALDP. However, as expected, the levels of this protein were greatly decreased. Taken together, our data suggest that some less severe or late-onset forms of X-ALD associated with splice mutations result from the production of small amounts of normal ALDP. It is proposed that the quantification of ALDP levels in these patients could provide important insights concerning the correlation between clinical phenotype and amount of normal ALDP.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters / analysis*
  • ATP-Binding Cassette Transporters / genetics*
  • Adrenoleukodystrophy / genetics*
  • Adult
  • Age of Onset
  • Humans
  • Male
  • Mutation
  • RNA Splicing / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribonucleoproteins
  • Sex Chromosome Aberrations*
  • X Chromosome*


  • ABCD1 protein, human
  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters
  • Ribonucleoproteins
  • messenger ribonucleoprotein