智力低下儿童染色体脆性部位与临床表现初步研究

Preliminary Investigation of Chromosome Fragility Sites with Clinical Situation in Mentally Retardation Children

目的:探讨智力低下儿童染色体脆性部位与临床表现的关系。方法:患儿年龄为4～15岁,智力测定采用学龄前儿童小韦氏(Wppsi)、学龄儿童用大韦氏(WiscR),同时进行社会生存能力测试。MR分级根据美国精神学会和世界卫生组织所颁布的标准(DSM-1、ICD-8)。智商均在正常标准以下的患儿及父母均做染色体G带高分辨与脆性位点检查。结果:280例先天智力低下儿童中染色体数目或结构异常的40例(14.29%);不同脆性位点表达阳性82例(29.29%);患儿与其父或母同一脆性位点表达阳性37例(13.21%);染色体脆性位点FraXq27、FraXq26、FraXq25、FraXq24的13例(4.64%);患儿脆性位点表达阴性,而父母表达阳性的14例(5%);脆性位点表达阴性94例(33.57%)。结论:脆性位点的异常甲基化与智力低下临床表型有着密切的关系;FraXq26、FraXq25、FraXq24可能与MR有关,而且可能是脆性X变异体,是一种新的突变;脆性位点的DNA突变点在配子或合子形成过程中,发生异常甲基化的同时,位置也可能发生“基因漂移”改变;脆性位点越多越复杂,患儿的智力低下的程度越低;同一脆性位点表达率的高低却与智力低下的程度无明显的正比关系。

Objective： To explore relationship between the chromosome fragility sites and clinical situation among mentally retardation children, Methods ：280 mentally retardation children aged 4 - 15, were divided into different grade according to DSM - 1 and ICD -8 by WISC. The chromosomes and fragile sites in mentally retardation children and their parents were examined. Results： There were 40 cases （ 14, 29% ） with chromosomal abnormalities in number or structure, 82 cases （29.29%） with positive expression in various fragile sites, 37 cases （ 13.21 % ） with positive expression in same fragile sites among children and their parnts, 13 cases （4.64%） with chromosome fragile sites on FraXq27 ,FraXq26 ,FraXq25 .FraXq24, 14 cases （5%） with negative expression in children＇s fragile sites and positive expressiolnin their parents fragile sites, and 94 cases （33.5%） with negative expression in the fragile sites, Conclusion： Abnormal methylation of chromosome fragility sites is related closely to clinical mentally retardation expression, FraXq27, FraXq26, FraXq25 and FraXq24 are possibly related to MR and they are probably variant of frggile X chromosome, a new gene mutation. At the same time, DNA mutation position in fragile sites was skewing with abnormal methylation during gametes or zygotes formation. The more complex the chromosome fragility sites are, the lower mental retardation level of children is. It is no direct relationship between degree of expression in same chromosome fragility sites and mental retardation level of children.