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.