肾上腺脑白质营养不良外显子6、7、8基因突变研究

Mutation detected in patients with X-linked recessive adrenoleukodystrophy in exon6.exon7 and exon8 gene

目的 探讨中国人X -连锁隐性遗传肾上腺脑白质营养不良 (adrenoleukodystrophy)的分子发病机理。方法 应用聚合酶链反应 (polymerasechainreaction)结合DNA测序技术 (DNAsequencing) ,对收集的 6例患者、患者母亲及 2 0名正常对照的ALD基因外显子 6、7、8及其侧翼进行突变检测。结果 检出一例患者在ALD基因外显子 6发生了Val5 17Ile(G→A)的碱基错义突变 ;另一侧患者在ALD基因外显子 7发生了Gln5 5 6Arg(A→G)的碱基错义突变。ALD基因突变合成异常不稳定的蛋白 (ALDP) ,从而使VLCFA在脑白质、肾上腺及血浆聚集增多 ,导致疾病发生。结论 ALD基因突变是中国人X -连锁隐性遗传ALD发病原因之一。

Objective: To elucidate the molecular mechanism of X-linked adrenoleukodystrophy in China. Methods: Polymerase china reaction in exon 6. exon 7. exon8 and their flanking sequences and direct DNA sequencing of adrenoleukodystrophy(ALD) gene were performed in six patients, their mothers and twenty normal individuals. Results: A missense mutation were identified in exon6(Val517Ile G→A). The other missense mutation were identified in exon7(Gln556Arg A→G). This mutation causes unstable and abnormal ALD protein. Defective β-oxidation of very long chain fatty acids (VLCFAS) in peroxosome has been shown to lead to an accumulation of VLCFAS in the central nerves systems, adrenal gland and blood. Conclusion: Mutations of ALD gene is the causes of X-linked recessive adrenoleukodystrophy in Chinese population.