临床意义未知的拷贝数变异分析提示9p23区域可能和智力发育障碍相关

目的对全基因组拷贝数芯片分析(CMA)中临床意义未知的拷贝数变异(VUS)与患者表型进行分析,试图寻找和表型相关的拷贝数变异区域。方法对38例全基因组芯片未见明显结构性变化患者的结果和详细表型(智力水平、发育水平、面容是否异常和头围是否正常)进行分组统计,分析临床意义VUS和表型之间的联系,并在45名正常对照中验证拷贝数变异,排除正常多态性可能。结果发现9号染色体p23区域的缺失在智力落后患者与智力水平正常但合并其它表型患者中出现,差异有明显的统计学意义(P0.01),并且在正常对照中未见该区域的缺失,提示9p23区域可能和儿童智力发育相关。结论临床意义VUS分析可以帮助提示和患者表型相关的信息,确认临床意义VUS将有助于提高基因组芯片的诊断效率,揭示新的可疑致病区域。

Analysis of variants with unknown significance indicating 9p23 as a candidate locus for intellectual development impairment

Objective To find out copy number variants as candidate loci by analyzing variants with unknown significance （VUS）and phenotypes in chromosomal microarray analysis （CMA）.Methods The VUS and phenotypes in chromosomal microarray for 38 patients were analyzed statistically and classified into different groups （intellectual level,development level,facial abnormality and head circumference abnormality）to evaluate the relation between VUS and phenotypes.A total of 45 healthy controls were used in the study to validate polymorphism copy number variants. Results Deletions on 9p23 region had significantly higher frequency in intellectual development impairment patients than patients with normal intellectual level with statistical significance （P ＆lt;0.01 ）,and 9p23 region change had not been detected in 45 healthy controls,indicating this locus to be related with children′s intellectual development impairment.Conclusions The analysis of VUS can offer the reference between phenotypes and copy number variants. The confirmation of VUS can help with enhancing the diagnostic ability of chromosomal microarray and find new pathogenic chromosomal locus.