肾上腺脑白质营养不良外显子1,5基因突变分析  

Analysis on mutation of adrenoleukodystrophy gene in exon 1 and exon 5

作　　者：施晓容[1] 陈育才[1] 谢文煌[1] 黄梅芳[1] 侯晓君[1] 王柠[1] 

机构地区：[1]福建医科大学附属第一医院儿科,福州350004

出　　处：《中华医学遗传学杂志》2003年第1期43-45,共3页Chinese Journal of Medical Genetics

基　　金：福建省卫生厅基金 (9940 69)~~

摘　　要：目的　探讨中国人性染色体隐性遗传肾上腺脑白质营养不良 (adrenoleukodystrophy,AL D)的分子发病机理。方法　应用聚合酶链反应结合 DNA测序技术 ,对 4例患者、患者母亲及 2 0名正常对照者的 AL D基因外显子 1、外显子 5及其侧翼进行突变检测。结果　发现 1例患者在 AL D基因外显子 5内含子 5交界处发生了 1875 G→ A突变 ,这种突变可能导致外显子 5和外显子 6剪接异常 ,合成异常蛋白 ,从而使极长链脂肪酸在脑白质、肾上腺及血浆聚集增多 ,导致疾病发生。结论　 AL D基因内含子 5的 5′剪切点突变 ,导致外显子 5和外显子Objective: To elucidate the molecular mechanism of X-linked adrenoleukodystrophy (ALD) in Chinese. Methods: Polymerase chain reaction in exon 1, exon 5 and their flanking sequences and direct DNA sequencing of ALD gene were performed in four patients, their mothers and twenty normal individuals as controls. Results: A splice mutation was identified in the interface of exon 5 and intron 5 (1875 G &rarr A). This splice mutation in 5′ end of intron 5 might lead to abnormal splice in exon 5 and exon 6 and bring about unstable and abnormal ALD protein; the lignoceryl CoA ligase could not transport very long chain fatty acids (VLCFA) into peroxisome and could not function normally; consequently, defective β-oxidation of VLCFA in peroxisome could result in an accumulation of VLCFAS in the central nervous system, adrenal gland and blood. Conclusion: The splice mutation in 5′ end of intron 5 leading to abnormal splice in exon 5 and exon 6 appears to be one of the causes of X-linked recessive adrenoleukodystrophy.

关 键 词：肾上腺脑白质营养不良 聚合酶链反应 DNA序列分析 基因突变 

分 类 号：R748[医药卫生—神经病学与精神病学]