检测不明原因智力障碍/脑发育迟缓儿染色体亚端粒重组突变  

Detection of Subtelomeric Recombination in Patients with Unexplained Retardation of Intellectual and Brain Development

作　　者：季涛云[1] 吴晔[1] 王静敏[1] 肖静[2] 王慧芳[1] 李洁[1] 赵海娟[1] 杨艳玲[1] 秦炯[1] 吴希如[1] 姜玉武[1] 

机构地区：[1]北京大学第一医院儿科,100034 [2]首都医科大学附属北京儿童医院神经内科

出　　处：《国际生殖健康／计划生育杂志》2011年第3期173-177,194,F0003,共7页Journal of International Reproductive Health/Family Planning

基　　金：国家重点基础研究发展计划(973计划)项目(2007CB511902);北京市自然科学基金重点项目(7081004)

摘　　要：目的：联合应用多重连接依赖的探针扩增技术（multiplex ligation-dependent probeamplification,MLPA）和Affimetrix SNP 6.0芯片检测并精确定位染色体亚端粒拷贝数异常,对不明原因智力障碍/脑发育迟缓（mental retardation/developmental delay,MR/DD）进行病因学研究。方法：收集不明原因MR/DD患儿,通过MLPA筛查亚端粒区拷贝数,检测到拷贝数异常者（阳性患儿）进一步检测是否为新发,对新发拷贝数异常者行AffymetrixSNP 6.0芯片验证并精确定位拷贝数异常范围。结果：阳性患儿41例（入组共627例）,阳性率6.5%。其中30例单一缺失,6例单一重复,5例同时存在缺失及重复。缺失长度为0.6~12 Mb,包含5~202个基因;重复长度为0.26~11 Mb,包含6~143个基因。与阴性患儿（未检测到拷贝数异常）比,阳性患儿体表畸形（75.6%）和其他先天畸形（51.2%）发生率较高,差别有统计学意义（P〈0.05）。结论：亚端粒区拷贝数异常是不明原因MR/DD的重要病因,为遗传咨询提供了基础。4例拷贝数缺失片段和1例拷贝数重复片段的区域较小。亚端粒区拷贝数异常范围的精确定位为寻找MR/DD致病基因并进行深入的机制研究提供了线索。Objective： Combined using MLPA and Affymetrix SNP 6.0 chip to detect and fine mapping subtelomeric rearrangement in patients with unexplained MR/DD,finally to provide new methods and evidence for the etiologic diagnosis of MR/DD in China.Methods： 1.Collect unexplained MR/DD patients,2.MLPA combined with Affymetrix SNP 6.0 chip was performed to detect and fine mapping subtelomeric rearrangements in patients.Results：The subtelomeric aberrations were identified in 41 patients,with a detection rate of 6.5%.30 patients had simple deletions,6 had simple duplications and 5 with both deletions and duplications.The sizes of the deletions varied from 0.6 to 12 Mb,with 5-202 genes inside.Duplicated regions were 0.26 to 11 Mb,with 6-143 genes inside.Compare with the MLPA negative patients,the incidence of appearance malformations（75.6%） and other congenital malformations（51.2%） are significantly higher in the MPLA positive patients（P0.05）.Conclusions： Subtelomeric copy number variation is an important cause of unexplained MR/DD.Four deleted subtelomeric regions and one duplicated region found were smaller than any previously reported,which will be helpful for further defining the candidate dosage sensitive gene associated with MD/DD.Subtelomeric aberrations were detected in 6.5% of Chinese children with unexplained MR/DD.5 complex subtelomeric aberretions have not been reported.Four deleted subtelomeric regions and one duplicated region found were smaller than any previously reported,which will be helpful for further defining the candidate dosage sensitive gene associated with MR/DD.

关 键 词：精神发育迟滞 发育障碍 端粒 基因缺失 基因重排 

分 类 号：R749.94[医药卫生—神经病学与精神病学]