Large deletion of the peroxisomal acyl-CoA oxidase gene in pseudoneonatal adrenoleukodystrophy.
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.
University Children's Hospital Wilhelmina Kinderziekenhuis, University Hospital Utrecht, The Netherlands.
B
B
Fournier
J M
JM
Saudubray
B
B
Benichou
S
S
Lyonnet
A
A
Munnich
H
H
Clevers
B T
BT
Poll-The
D042962:Acyl-CoA Oxidase; D000326:Adrenoleukodystrophy / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D018076:DNA, Complementary / Q000737:chemistry / Q000302:isolation & purification; D017353:Gene Deletion; D006801:Humans; D008830:Microbodies / Q000201:enzymology*; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000172:deficiency / Q000235:genetics*; D051381:Rats
D018076:DNA, Complementary; D010088:Oxidoreductases; D042962:Acyl-CoA Oxidase