智力发育迟缓患儿染色体亚端粒区研究

Study on subtelomeric aberrations in children with mental retardation

目的联合应用多重连接依赖探针扩增技术（multiplex ligation—dependent probe amplmcation，MLPA）对不明原因智力发育迟缓（mental retardation，MR）患儿进行病因学研究，探讨本地区MR患儿亚端粒区异常与表型的关系。方法将2009年7月至2011年12月在广东省妇幼保健院就诊的原因不明的67例MR患儿纳入研究，采集患儿及其父母外周血，提取基因组DNA，通过MLPA筛查，检测亚端粒区异常情况，用2种MLPA试剂盒（P070和P036）进行相互验证，异常者进一步分析其父母染色体亚端粒区情况，确定是否新发；根据检测结果与临床表现，分析染色体亚端粒区重排与临床表型的相关性。结果67例MR患儿纳入研究，男42例，女25例；年龄6个月-15岁；IQ20—70分，轻度MR（IQ≥50分）47例，中重度MR（IQ〈50分）20例；7例有抽搐史，体表畸形24例，脏器畸形18例。经MLPA检测发现4例亚端粒拷贝数异常，检出率5．97％，4例均为新发病例。亚端粒异常阳性和阴性患儿的性别比例、年龄、是否有抽搐病史等进行比较，差异均无统计学意义（P均〉0．05）。中重度MR患儿亚端粒异常比例（20．0％）较轻度高；阳性患儿在生长发育、体格畸形及脏器畸形等方面的异常比例均较阴性患儿高，差异均有统计学意义（P均〈0．05）。结论染色体亚端粒区异常可能是不明原因MR的重要病因之一；原因不明智力低下者，应对其亚端粒区进行检测，为寻找可能的病因提供线索，为遗传咨询提供依据。

Objective To make an etiology study on children with unexplained mental retardation （MR） by using combined multiplex ligation-dependent probe amplification （MLPA） , and to explore associations between subtelomeric aberrations and phenotypes in local children. Methods Sixty-seven children with unexplained MR were enrolled in study group from Jul. 2009 to Dec. 2011 in Guangdong Women and Children＇s Hospital. Peripheral blood of patients and their parents were collected as samples of subtelomeric test by MLPA. Two kinds of probes of MLPA were combined to verify the aberration resuhs. After confirmed test the parent of positive children were tested by the same way, then to analyze associations between test data and the clinical feature. Results Among sixty-seven children enrolled ih the study aged 6 months to 15 years,where were 42 male and 25 female;the intelligence of 47 children belonged to mild de- gree （IQ ≥ 50 scores）, that of 20 children belonged to severe degree （IQ 〈 50 scores） ;7 patients had convulsion histo- ry ,24 patients had malformation, 18 cases had idiopathic organ aberrations. Four patients had aberration copies in subte- lomeric region by MLPA test,the detection rate was 5.97% ,4 patients were novel cases. There was no significant differ- ences in genders, age and convulsion history between positive and negative children （ all P 〉 0.05 ）. The aberration rate in moderate to severe degree group was higher than those mild degree group. The rates of features including physical developmental retardation, malformation and organ aberrations in positive children were higher than those of the negative cases. There were significant differences between the 2 severity groups （ all P 〈 0.05 ）. Conclusions Aberrations in subtelomerie region can be one of the important causes of unexplained MR. The MR patients were supposed to have subtelomerie region tested so as to provide the evidence for diagnosis and genetic counseling.