不明原因智力障碍与癫痫伴智力障碍患儿的基因拷贝数变异比较研究

Comparison of genome-wide copy number variations between patients with unexplained mental retardation and epilepsy with mental retardation

目的分析不明原因智力障碍(U-MR)与癫痫伴智力障碍(E-MR)患儿的分子遗传基础差异,探讨单核苷酸多态性微阵列分析技术(a SNP)在不同类型疾病检测中的应用价值。方法选择2015-06～2017-12间98例U-MR和90例E-MR患儿,提取其外周血DNA,采用a SNP技术进行全基因组拷贝数变异(CNVs)检测,分别对U-MR和E-MR患儿进行CNVs致病性比较分析。结果 98例U-MR患儿中10例检出CNVs,检出率为10. 2%,CNVs的片段范围0. 6-36 Mb; 90例E-MR患儿中3例检出CNVs,检出率为3. 33%。其中,U-MR患儿检出已知致病的微缺失/微重复综合征1例,明确致病的微缺失/微重复(非综合征) 4例,染色体数目异常1例,临床意义不明4例; E-MR患儿检出染色体数目异常2例,临床意义不明1例。结论微阵列技术a SNP对不明原因智力障碍患儿的检测微缺失/微重复CNVs更敏感,提示微阵列分析技术有望作为临床不明原因智力障碍遗传学早期筛查诊断的工具,但需将来进一步证实。

Objective To investigate the difference on genetic basis of patients with unexplained mental retardation(U-MR) and epilepsy with mental retardation(E-MR), and to assess the application of array-based single nucleotide polymorphisms(aSNP) in molecular diagnosis of U-MR and E-MR patients. Methods Ninety- eight U-MR patients and ninety E-MR patients from June 2015 to December 2017 were enrolled. Genomic DNA was extracted from peripheral blood and genome-wide copy number variations(CNVs) were analyzed with aSNP technology. The pathogenicity of CNVs between U- MR and E-MR patients was compared. Results Ten cases of 98 U-MR patients were found to have CNVs with genomic alterations and the detection rate was 10.2%. The size of CNVs segment ranged from 0.6 Mb to 36 Mb. Three cases of 90 E-MR patients were found to have CNVs with genomic alterations and the detection rate was 3.33%. The CNVs of U-MR included one case of microdeletions/microduplications associated with known syndromes, four cases of microdeletions and microduplications with clear clinical relevance(non-syndrome), one case of numerical chromosome aberration, and four cases of unknown clinical significance. The CNVs of E-MR included two cases of numerical chromosome aberration, and one case of unknown clinical significance. Conclusion The aSNP technology is more sensitive to detect the microdeletions/microduplications CNVs of U-MR patients. It suggests that the aSNP technology is expected to be used as a early screening diagnosis tool for clinical genetics of U-MR, but it needs to be further confirmed in the future.