CAJ | 학술논문

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.
목적 탐토화남지구불명원인지력저하환자중취성X지력저하기인FMR1화FMR2기인돌변정황.방법 선택자2009년10월지2014년4월취진우엄주의과대학부속제이의원、장사시제삼의원신경발육혹전간문진、엄주시해주구특수학교적화남지구불명원인지력저하적72례환자(남65례、녀7례),채용PCR대FMR1기인5'비번역구(5'-UTR)적(CGG)n화FMR2기인(CCG)n돌변진행사사;대미능확출목적편단혹녀성가의개체진일보행Southern blotting급모세관전영측서소묘분석증실시부구유전돌변;대FMR1기인(CGG)n급FMR2기인(CCG)n량자도정상적환자재진일보대FMR1기인외현자급3'-UTR구단채용상규PCR방법확증측서사사돌변,최후장FMR1기인전돌변빈솔여아구미불동국가화지구정황진행통계분석.결과 72례환자중공사사도8개유의의림상가계:6개전돌변가계(선증자위1녀5남),전돌변가계중공명학진단FMR1기인전돌변환자12례(포괄2례감합체환자)、2례전돌변모친;령유1대FMR1기인편단결실모자화1대과도구모자.FMR1기인전돌변급결실돌변점지력저하환자적9.7％(7/72);남성지력저하환자중FMR1기인돌변비례위9.2％(6/65);화발체국가혹지구상비,FMR1기인돌변솔차이유통계학의의(P＜0.05).재연구대상중몰유발현FMR1기인변이외현자급3'UTR구역변이급FMR2기인전돌변.결론 상대우발체국가혹지구,화남지구지력저하인군중FMR1적돌변솔교고;대불명원인지력저하가계(가족사)적사사,가이제고취성X종합정진단적양성솔;FMR1기인외현자돌변、3'UTR구역변이급FMR2기인전돌변불시지력저하환자적상견원인.
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.