4个肾上腺脑白质营养不良家系的基因诊断  

Gene diagnosis of four Chinese pedigrees with X-linked adrenoleukodystrophy

作　　者：王志红[1] 黄梁浒[1] 兰风华[1] 

机构地区：[1]南京军区福州总医院全军医学检验中心,福州350025

出　　处：《中国优生与遗传杂志》2007年第10期39-41,80,共4页Chinese Journal of Birth Health & Heredity

摘　　要：目的对4个肾上腺脑白质营养不良家系进行基因突变分析。方法应用RT-PCR技术,对4个患者的AB-CD1基因编码区,分4个片段进行扩增并对PCR产物直接测序。应用变性高效液相色谱技术、PCR-限制性酶切等方法分析相应的基因组DNA,进一步确证ABCD1的突变位点。结果在3名肾上腺脑白质营养不良患者的ABCD1基因上,存在2个不同的碱基置换(807G>A和2113T>C)和1个碱基插入(1126insGCCATCG),分别造成2个错义突变(A141T和L576P)和1个移码突变(fsI246);在患儿1母亲的一个ABCD1等位基因上存在1801-1802位碱基缺失,造成移码突变(fsE471),另一个等位基因未发现突变。结论在中国人ALD患者中发现2个新的ABCD1基因突变(fsI246、L576P)。不同家系具有不同的突变位点,且突变类型和表型之间无特殊的相关性。Objective： To identify the mutational genotype of four Chinese families with X -linked adrenoleukodystrophy （X- ALD） . Methods ： The coding region of ABCD1 gene of four patients was amplified in 4 segments by PCR after reverse transcription using RT - PCR technology. The PCR products were purified and directly sequenced. To confirm the mutations, the genomic DNA was analyzed by PCR - restrictive digestion or denaturing high performance liquid chromatography. Results ： Two base substitutions （ 807G 〉 A and 2113T 〉 C）, one base deletion （1801delAG） and one base insertion （1126insGCCATCG） were identified in four X -ALD pedigrees, which resulted in two missense mutations （A141T and L576P） and two frame shift mutations （fs E471 and fs 1246）. Conclusion： Two novel ABCD1 mutations, which were fs I246 and L576P, were detected in Chinese X -ALD patients. There were different ABCD1 gene mutations in different pedigrees and no obvious correlation between genotype and phenotype was found.

关 键 词：肾上腺脑白质营养不良 ABCD1基因 基因突变 变性高效液相色谱 

分 类 号：R450[医药卫生—治疗学]