三例Kleefstra综合征患儿的基因变异分析

目的:对3例Kleefstra综合征患儿进行 EHMT1基因变异分析，探讨其可能的致病原因。 方法:采集患儿及其父母的外周血进行全外显子测序(whole exome sequencing，WES)，其中基因拷贝数变异(copy number variation, CNV)应用Realtime-PC...

Genetic analysis of three patients with Kleefstra syndrome

Objective To analyze the clinical and genetic features of three patient diagnosed with Kleefstra syndrome.Methods Whole exome sequencing(WES)was carried out for the probands and their parents.Suspected variants were validated by Sanger sequencing.Copy number variations(CNV)were detected by CNV-seq and validated by real-time PCR.Results Proband 1 was found to carry a de novo heterogeneous variant(c.823+1G>T)of the EHMT1 gene,which may affect its expression.Based on the guidelines of the American College of Medical Genetics and Genomics,the variant was predicted to be pathogenic(PVS1+PS2+PM2).Proband 2 was found to carry a de novo missense variant c.439C>G(p.L147V)of the EHMT1 gene,which was predicted to be likely pathogenic(PS2+PM1+PM2+PP3).Proband 3 was found to carry a heterozygous 520 kb deletion at 9q34.3 by CNV-seq.The deletion has encompassed the whole of the EHMT1 gene.Real-time PCR has detected no CNV of this region in her parents.Conclusion Variants of the EHMT1 gene probably underlay the disease in these paients.Genetic testing has provided a basis for their clinical diagnosis.