Adrenoleukodystrophy: overlapping deletions point to a gene location in Xq28

Adrenoleukodystrophy is a lethal X-linked neurodegenerative disorder which maps close to the red/green color pigment gene cluster in Xq28. We have reported a broad spectrum of color pigment gene changes in adrenoleukodystrophy patients, indicating that the genes may be quite close together. We now have used anonymous DNA probes centromeric to the color pigment gene cluster to analyze patients from 59 adrenoleukodystrophy kindreds. All patients showed normal hybridization using probe Fr9, 30 kb centromeric to the color pigment genes. However, using probe Fr11, 100 kb further centromeric, we found overlapping deletions in 2 patients. We isolated conventional and cosmid genomic clones encompassing 24 kb surrounding Fr11; the clones and map derived from this region localize the telomeric ends of the two deletions to distinct positions 8 kb apart. These overlapping deletions implicate this specific region as a likely site for the ALD gene.