GENOMIC ORGANIZATION OF THE ADRENOLEUKODYSTROPHY GENE

Adrenoleukodystrophy (ALD), the most frequent peroxisomal disorder, is a severe neurodegenerative disease associated with an impairment of v ery long chain fatty acids beta-oxidation. We have recently identified by positional cloning the gene responsible for ALD, located in Xq28. It encodes a new member of the ''ABC'' superfamily of membrane-associa ted transporters that shows, in particular, significant homology to th e 70-kDa peroxisomal membrane protein (PMP70). We report here a detail ed characterization of the AT,D gene structure. It extends over 21 kb and consists of 10 exons. To facilitate the detection of mutations in ALD patients, we have determined the intronic sequences flanking the e xons as well as the sequence of the 3' untranslated region and of the immediate 5' promoter region. Sequences present in distal exons cross- hybridize strongly to additional sequences in the human genome. The AL D gene has been positioned on a pulsed-field map between DXS15 and the L1CAM gene, about 650 kb upstream from the color pigment genes. The f requent occurrence of color vision anomalies observed in patients with adrenomyeloneuropathy (the adult onset form of ALD) thus does not rep resent a contiguous gene syndrome but a secondary manifestation of ALD . (C) 1994 Academic Press, Inc.