Menkes病患儿ATP7A基因突变及X染色体失活分析  

Analysis of ATP7A Gene in Patients with Menkes Disease and X Chromosome Inactivation in a Case with Menkes Disease

作　　者：赵程峰[1,2,3,4,5] 王静敏[1] 王菊莉[3] 黄琼辉[1] 邓艳华[1] 吴晔[1] 姜玉武[1] 

机构地区：[1]北京大学第一医院儿科 [2]佳木斯大学康复医学院 [3]佳木斯市中心医院癫痫科 [4]佳木斯大学第三附属医院 [5]佳木斯大学儿童康复神经实验室

出　　处：《中国伤残医学》2013年第5期37-41,共5页Chinese Journal of Trauma and Disability Medicine

基　　金：黑龙江省佳木斯大学研究生创新资助项(YJSCX2012-024JD);北京大学第一医院归国人员启动基金项目资助

摘　　要：目的:分析并确立1例Menkes病的ATP7A基因突变,并从X染色体失活角度探讨突变的亲源性和ATP7A的致病机制。方法:首先搜集该例临床典型Menkes病患儿及其父母的外周血提取基因组DNA,分别对患儿及父母的外周血DNA进行PCR扩增,通过DNA测序和琼脂糖凝胶电泳判定患儿突变的亲源性;用雄激素受体基因(AR)的三核苷酸多态性进行基因型分析判定X染色体失活是否发生偏斜。结果:基因诊断确诊1例Menkes病患儿,DNA直接测序检测结果为c.3045delT(p.T1016fsX1018)缺失突变,其母亲为携带者,其父亲无异常;对该例基因确诊的Menkes病患儿母亲行X染色体失活分析,发现ATP7A基因突变携带者的X染色体高度非随机失活(P1m,100:0)。结论:本研究通过分子遗传学分析发现该例患儿为缺失突变,可确诊为Menkes病。经X染色体失活分析对ATP7A基因致病机制做初步的探讨,证明了Menkes病患儿的母亲X染色体失活可能为非随机失活,表现为母亲优先失活有突变的X染色体。Objective：To analyze and characterize the genetic features of a chinese family with Menkes disease. Familial cases of Menkes disease are rare and are due to X-chromosomal inheritance fron a carrier mother. To explain the pathogenic mechanism of the sex-limited expression of Menkes disease, we have analyzed the parental origin of mutations and the XCL status in cases with Menkes disease due to ATP7A molecular defects. Methods： Genomic DNAs from the patient and her parents were extracted using standard procedures from the peripheral blood leukocytes, PCR and DNA direct sequencing were employed to analyze all of the 7 exons of the DCX gene to determine the gene mutation. The degree of XCL and its direction relative to the X chromosome parent of origin were measured in DNA prepared from peripheral blood leucocytes by analyzing CAG repeat polymorphism in the androgen receptor gene （AR）. Results： PCR detected a deletion of c.3045delT（p.T1016fsX1018）,while her mother was a carrier for the mutation. The cases had a skewed XCL pattern and he favor expression of the maternal origin allele. Conclusion：The proband carried a deletion c.3045delT（p.T1016fsX1018）,and his mother is normal, consistent with recessive inheritance. The skewed XCL pattern was the main XCL pattern in Menkes disease patients. The priority inactive X chromosome was mainly of maternal origin.

关 键 词：MENKES病 X染色体失活 基因 遗传 ATP7A 

分 类 号：R446[医药卫生—诊断学]