Mutational analysis of patients with X-linked adrenoleukodystrophy

Fernando Kok, Sylvia Neumann, Claude Olivier Sarde, Siqun Zheng, Kuei Hua Wu, He Ming Wei, James Bergin, Paul A Watkins, Stephen J Gould, George Henry Sack, Hugo Moser, Jean Louis Mandel, Kirby D. Smith


Adrenoleukodystrophy (ALD) is an X-linked neurodegenerative disorder characterized by elevated very long chain fatty acid (VLCFA) levels, reduced activity of peroxisomal VLCFA-CoA ligase, and variable phenotypic expression. A putative gene for ALD was recently identified and surprisingly encodes a protein (ALDP) that belongs to a family of transmembrane transporters regulated or activated by ATP (the ABC proteins). We have examined genomic DNA from ALD probands for mutations in the putative ALD gene. We detected large deletions of the carboxyl-terminal portion of the gene in 4 of 112 probands. Twenty-five of the ALD probands whose ALD genes appeared normal by Southern blot analysis were surveyed for mutations by Single Strand Conformation Polymorphism (SSCP) procedures and DNA sequence analysis. SSCP variants were detected in 22 probands and none in 60 X-chromosomes from normal individuals. Mutations were detected in all of the ALD probands. The mutations were distributed throughout the gene and did not correlate with phenotype. Approximately half were non-recurrent missense mutations of which 64% occurred in CpG dinucleotides. There was a cluster of frameshift mutations in a small region of exon 5, including an identical AG deletion in 7 unrelated probands. These data strongly support the supposition that mutations in the putative ALD gene result in ALD.

Original languageEnglish (US)
Pages (from-to)104-115
Number of pages12
JournalHuman Mutation
Issue number2
Publication statusPublished - 1995



  • Adrenoleukodystrophy
  • ALD
  • Immunofluorescence
  • Mutation detection

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Mutational analysis of patients with X-linked adrenoleukodystrophy. / Kok, Fernando; Neumann, Sylvia; Sarde, Claude Olivier; Zheng, Siqun; Wu, Kuei Hua; Wei, He Ming; Bergin, James; Watkins, Paul A; Gould, Stephen J; Sack, George Henry; Moser, Hugo; Mandel, Jean Louis; Smith, Kirby D.

In: Human Mutation, Vol. 6, No. 2, 1995, p. 104-115.

Research output: Contribution to journalArticle