Large Deletion of the Peroxisomal acyl-CoA Oxidase Gene in Pseudoneonatal Adrenoleukodystrophy

J Clin Invest. 1994 Aug;94(2):526-31. doi: 10.1172/JCI117365.

Abstract

We have cloned the cDNA encoding human peroxisomal acyl-CoA oxidase, the first enzyme in the peroxisomal beta-oxidation of very long chain fatty acids. Its nucleotide sequence was found to be highly homologous (85%) to the rat cDNA counterpart. An 88% homology between rat and human was found in the COOH-terminal end of the cDNA which includes the Ser-Lys-Leu peroxisomal targeting signal common to many peroxisomal proteins. The gene spans approximately 30-40 kb and is poorly polymorphic. Southern blot analyses were performed in two previously reported siblings with an isolated peroxisomal acyl-CoA oxidase deficiency (pseudoneonatal adrenoleukodystrophy). A deletion of at least 17 kb, starting down-stream from exon 2 and extending beyond the 3' end of the gene, was observed in the two patients. These observations provide a molecular basis for the observed acyl-CoA oxidase deficiency in our family. In addition, our study will enable the characterization of the genetic defect in unrelated families with suspected acyl-CoA oxidase disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl-CoA Oxidase
  • Adrenoleukodystrophy / genetics*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Southern
  • DNA, Complementary / chemistry
  • DNA, Complementary / isolation & purification
  • Gene Deletion*
  • Humans
  • Microbodies / enzymology*
  • Molecular Sequence Data
  • Oxidoreductases / deficiency
  • Oxidoreductases / genetics*
  • Rats

Substances

  • DNA, Complementary
  • Oxidoreductases
  • Acyl-CoA Oxidase

Associated data

  • GENBANK/X71440