X-linked adrenoleukodystrophy: molecular and functional analysis of the ABCD1 gene in Argentinean patients

PLoS One. 2012;7(12):e52635. doi: 10.1371/journal.pone.0052635. Epub 2012 Dec 31.


X-linked adrenoleukodystrophy (X-ALD) is an inherited metabolic disease associated with mutations in the ABCD1 gene that encodes an ATP-binding cassette transporter protein, ALDP. The disease is characterized by increased concentrations of very long-chain fatty acids (VLCFAs) in plasma and in adrenal, testicular and nervous tissues, due to a defect in peroxisomal VLCFA β-oxidation. In the present study, we analyzed 10 male patients and 17 female carriers from 10 unrelated pedigrees with X-ALD from Argentina. By sequencing the ABCD1 we detected 9 different mutations, 8 of which were novel. These new mutations were verified by a combination of methods that included both functional (western blot and peroxisomal VLCFA β-oxidation) and bioinformatics analysis. The spectrum of novel mutations consists of 3 frameshift (p.Ser284fs*16, p.Glu380Argfs*21 and p.Thr254Argfs*82); a deletion (p.Ser572_Asp575del); a splicing mutation (c.1081+5G>C) and 3 missense mutations (p.Ala341Asp, p.His420Pro and p.Tyr547Cys). In one patient 2 changes were found: a known missense (p.His669Arg) and an unpublished amino acid substitution (p.Ala19Ser). In vitro studies suggest that p.Ala19Ser is a polymorphism. Moreover, we identified two novel intronic polymorphisms and two amino acid polymorphisms. In conclusion, this study extends the spectrum of mutation in X-ALD and facilitates the identification of heterozygous females.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters / genetics*
  • Adrenoleukodystrophy / genetics*
  • Amino Acid Sequence
  • Argentina
  • Base Sequence
  • Conserved Sequence
  • DNA Mutational Analysis
  • Exons
  • Female
  • Genetic Association Studies
  • Heterozygote
  • Humans
  • Introns
  • Male
  • Molecular Sequence Data
  • Mutation
  • RNA Splice Sites


  • ABCD1 protein, human
  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters
  • RNA Splice Sites

Grants and funding

This research was supported by a Grant for PICT 2010-FONCYT N°1116 PREST. BID 2437/OC-AR, Fundación Florencio Fiorini, Grant for Secretaría de Ciencia y Tecnología, Universidad Nacional de Córdoba (SECyT-UNC), Grant support: VZ MSM CR 0021620806, PRVOUK-P24/LF1/3, RVO-VFN64165/2012. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.