Willems P J, Vits L, Wanders R J, Coucke P J, Van der Auwera B J, Van Elsen A F, Raeymaekers P, Van Broeckhoven C, Schutgens R B, Dacremont G
Department of Medical Genetics, University of Antwerp-UIA, Wilrijk, Belgium.
Arch Neurol. 1990 Jun;47(6):665-9. doi: 10.1001/archneur.1990.00530060077022.
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.
我们展示了一个大家族，其中包含患有肾上腺脑白质营养不良（ALD）或肾上腺脊髓神经病（AMN）的患者。该谱系明确支持非新生儿型ALD/AMN的X连锁遗传模式。用位于Xq28的DNA标记进行分析表明，ALD和AMN均与相同的单倍型发生分离。这表明非新生儿型ALD和AMN是由Xq28上同一基因的突变引起的。此外，这还表明ALD和AMN之间的表型差异不一定是由于同一基因内不同突变导致的等位基因异质性的结果。在重组率为0.00时，ALD/AMN基因与DXS52处的多等位基因匿名DNA标记的最大连锁lod分数为3.0。这使得通过使用该标记进行DNA分析来进行产前或症状前诊断以及杂合子检测变得可靠。
