华南地区不明原因智力低下患者FMR1和FMR2基因突变分析  

Analysis of fragilex mental retardation 1 and fragilex mental retardation 2 gene mutations in intellectually disabled population of unknown causes in Southern China

作　　者：段现来 刘超 李啬夫 石奕武[3] 易咏红[3] 廖卫平[3] 

机构地区：[1]长沙市第三医院神经内科,410015 [2]长沙市第一医院神经内科,410005 [3]广州医科大学附属第二医院神经内科、广州医科大学神经科学研究所、神经遗传与离子通道省部共建教育部重点实验室,广州510260

出　　处：《中华神经医学杂志》2015年第5期477-482,共6页Chinese Journal of Neuromedicine

基　　金：国家自然科学基金面上项目（81171073、81471149）;长沙市第三医院学科人才培养基金（长三医发[2013]13号）

摘　　要：目的 探讨华南地区不明原因智力低下患者中脆性X智力低下基因FMR1和FMR2基因突变情况.方法 选择自2009年10月至2014年4月就诊于广州医科大学附属第二医院、长沙市第三医院神经发育或癫痫门诊、广州市海珠区特殊学校的华南地区不明原因智力低下的72例患者（男65例、女7例）,采用PCR对FMR1基因5＇非翻译区（5＇-UTR）的（CGG）n和FMR2基因（CCG）n突变进行筛查;对未能扩出目的片段或女性可疑个体进一步行Southern blotting及毛细管电泳测序扫描分析证实是否具有全突变;对FMR1基因（CGG）n及FMR2基因（CCG）n两者都正常的患者再进一步对FMR1基因外显子及3＇-UTR区段采用常规PCR方法扩增测序筛查突变,最后将FMR1基因全突变频率与亚欧美不同国家和地区情况进行统计分析.结果 72例患者中共筛查到8个有意义临床家系：6个全突变家系（先证者为1女5男）,全突变家系中共明确诊断FMR1基因全突变患者12例（包括2例嵌合体患者）、2例前突变母亲;另有1对FMR1基因片段缺失母子和1对过渡区母子.FMR1基因全突变及缺失突变占智力低下患者的9.7％（7/72）;男性智力低下患者中FMR1基因突变比例为9.2％（6/65）;和发达国家或地区相比,FMR1基因突变率差异有统计学意义（P＜0.05）.在研究对象中没有发现FMR1基因变异外显子及3＇UTR区域变异及FMR2基因全突变.结论 相对于发达国家或地区,华南地区智力低下人群中FMR1的突变率较高;对不明原因智力低下家系（家族史）的筛查,可以提高脆性X综合征诊断的阳性率;FMR1基因外显子突变、3＇UTR区域变异及FMR2基因全突变不是智力低下患者的常见原因.Objective To screen the fragilex mental retardation 1 （FMR1） gene mutations and explore the frequency of FMR1 gene mutation in the population with mental retardation in South China.Methods Seventy-two patients （65 males and 7 females） with suspected fragile X syndrome （FXS） in South China were enrolled in our hospitals from October 2009 to April 2014.The CGG trinucleotide repeats in 5＇UTR of FMR1 gene and CCG trinucleotide repeats in FMR2 gene were screened respectively by PCR.Southern blotting and capillary electrophoresis sequencing were performed in male patients without normal target bands and suspected female patients;patients with normal CGG alleles were,then,performed exons and 3＇-UTR ofFMR1 gene amplification and sequencing.The frequency of FMR1 gene mutation in patients with mental retardation in different countries and regions was compared with statistical analysis.Results Six pedigrees with full mutation （one female and five males being the probands）,one pedigree （mother and son） with FMR1 gene deletion and one pedigree （mother and son） with mutation in the transition region were identified in 72 patients with mental retardation.The prevalence of total mutation was 9.7% （7/72） and that in male patients was 9.2% （6/65）.These results showed significant differences in prevalence as compared with the results from different countries and areas （P〈0.05）;there were no variations in 3＇UTR ofFMR1 gene and FMR2 gene mutation in the patients with FXS-like phenotype.Conclusions FMR1 mutation frequency may be higher in mental retardation population in southem China as compared with that in developed countries or areas.Targeted screening on the unexplained mental retardation pedigrees （family history） can improve the diagnosis of FXS.Importantly,deletion mutations screening should also be performed in suspected FXS subjects with normal CGG repeats.

关 键 词：智力低下 脆性X综合征 FMR1基因 FMR2基因 全突变 

分 类 号：R741[医药卫生—神经病学与精神病学]