Boehm C D, Cutting G R, Lachtermacher M B, Moser H W, Chong S S
Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287, USA.
Mol Genet Metab. 1999 Feb;66(2):128-36. doi: 10.1006/mgme.1998.2779.
X-linked adrenoleukodystrophy is a serious and often fatal disorder, affecting the white matter of the nervous system, the adrenal cortex, and the testis. The gene mutated in X-ALD encodes a peroxisomal membrane protein, ALDP. The presence of very long chain fatty acids in plasma is highly diagnostic for affected males and carrier females, but exclusion of carrier status biochemically is unreliable. Molecular analysis of the X-ALD gene has the potential to either identify or rule out carrier status accurately, but is complicated by the existence of autosomal paralogs. We have developed and validated a robust DNA diagnostic test for this disorder involving nonnested genomic amplification of the X-ALD gene, followed by fluorescent dye-primer sequencing and analysis. This protocol provides a highly reliable means of determining carrier status in women at risk for transmitting X-ALD and is applicable to a clinical diagnostic laboratory.
X连锁肾上腺脑白质营养不良是一种严重且常致命的疾病，会影响神经系统的白质、肾上腺皮质和睾丸。在X连锁肾上腺脑白质营养不良中发生突变的基因编码一种过氧化物酶体膜蛋白，即肾上腺脑白质营养不良蛋白（ALDP）。血浆中极长链脂肪酸的存在对患病男性和携带致病基因的女性具有高度诊断价值，但通过生化方法排除携带状态并不可靠。对X连锁肾上腺脑白质营养不良基因进行分子分析有潜力准确识别或排除携带状态，但由于常染色体旁系同源基因的存在而变得复杂。我们已经开发并验证了一种针对该疾病的可靠DNA诊断测试，该测试包括对X连锁肾上腺脑白质营养不良基因进行非巢式基因组扩增，随后进行荧光染料引物测序和分析。该方案提供了一种高度可靠的方法来确定有传播X连锁肾上腺脑白质营养不良风险的女性的携带状态，适用于临床诊断实验室。
