摘要
目的:应用甲基CpG结合蛋白-2(methyl-CpG-binding protein 2,MECP2)基因突变筛查方法,检测孤独症患者的MECP2基因,探讨孤独症与MECP2基因的关系。方法:收集男性孤独症44例,均满足孤独症《美国精神障碍诊断和统计手册》第4版诊断标准,应用变性高效液相色谱(denaturing high performance liquid chromatography,DHPLC)筛查MECP2基因变异,并进行DNA测序鉴定。对存在MECP2基因错义突变的病例进行家系调查。结果:在44例患者中经DHPLC筛查阳性和DNA测序发现,4例患者存在不同的MECP2基因突变,包括c.590C>T(T197M)和c.602C>T(A201V)2种错义突变,以及c.1053C>G、c.897C>T 2种同义突变;17例的内含子3位于Exon 4前74位点C>T,为SNP(rs2071569);1例c.602C>T错义突变患者家系调查发现,突变来源于母亲及外祖父,母亲呈杂合子,为X染色体随机失活,母亲与外祖父智力均正常,外祖父有抑郁症。结论:在男性孤独症患者中,存在MECP2基因较高的变异率,MECP2基因在孤独症致病中可能起着一定作用,不除外是孤独症的易感基因。
Objective：To investigate mutations in the methyl-CpG-binding protein 2 （MECP2） gene in male autism patients by PCR, denaturing high-performance liquid chromatography （DHPLC） and se-quencing to explore the role of mutations in MECP2 in autism patients. Methods： We recruited DNA samples from 44 male autism patients who matched the Diagnostic and Statistical Manual of Mental Disor-ders, Fourth Edition （DMS-IV） standards. DHPLC was used to screen the mutations in MECP2 gene, and DNA sequencing was performed for the samples with positive DHPLC results. The family members were further investigated in the patients with missense mutations in MECP2 gene. Results： Four cases were found to have mutations in MECP2 gene, including missense mutations of c. 590C 〉 T（T197M） in one case and c. 602C 〉 T（A201V）in one case, and synonymous mutations of c. 1053C 〉 G in one case and c. 897 C 〉 T in one case. In addition, we found C 〉 T variation in intron 3 at the ＋ 74 bp before exon 4, a SNP （rs2071569） usually detected in Chinese population. In the case with c. 602C 〉 T（A201V） mutation, his mother and maternal grandfather had the same mutation. His mother had normal pheno-type, but his maternal grandfather had depressive disease. Conclusion： Mutations in MECP2 are present in male autism patients with relatively higher prevalence, suggesting that these mutations may play roles in the pathogenesis of autism.
出处
《北京大学学报（医学版）》
CAS
CSCD
北大核心
2013年第2期197-201,共5页
Journal of Peking University:Health Sciences
基金
北京市自然科学基金(7012019)资助~~
