Linkage of DNA markers at Xq28 to adrenoleukodystrophy and adrenomyeloneuropathy present within the same family

P. J. Willems, L. Vits, R. J. Wanders, P. J. Coucke, B. J. Van der Auwera, A. F. Van Elsen, P. Raeymaekers, C. Van Broeckhoven, R. B. Schutgens, G. Dacremont and al. et
Department of Medical Genetics, University of Antwerp-UIA, Wilrijk, Belgium.

We present a large kindred that contained patients with either adrenoleukodystrophy (ALD) or adrenomyeloneuropathy (AMN). The pedigree clearly supported the X-linked mode of inheritance of the nonneonatal form of ALD/AMN. Analysis with DNA markers at Xq28 suggested segregation of both ALD and AMN with an identical haplotype. This indicated that nonneonatal ALD and AMN are caused by a mutation in the same gene at Xq28. It showed, furthermore, that phenotypic differences between ALD and AMN are not necessarily the consequence of allelic heterogeneity due to different mutations within the same gene. The maximal lod score for linkage of the ALD/AMN gene and the multiallelic anonymous DNA marker at DXS52 was 3.0 at a recombination fraction of 0.00. This made a prenatal or presymptomatic diagnosis and heterozygote detection by DNA analysis with this marker reliable.