两例Rubinstein-Taybi综合征患儿的临床及遗传学分析

Clinical and genetic analysis of two cases with Rubinstein-Taybi syndrome

目的 总结2例Rubinstein-Taybi综合征患儿的临床及遗传学特点.方法 采集患儿及家属外周血样,对全外显子组进行高通量测序,用Sanger测序法验证结果.结果 两例患儿均有特殊面容、拇指和大趾宽扁、体格及智力发育迟滞等特征.高通量测序发现例1携带CREBBP基因c.3779+1G>A杂合变异,例2携带CREBBP基因c.5052_c.5053insT杂合变异,按美国医学遗传学会指南评级两种变异均为有害.变异1为已知致病突变,变异2为新突变.结论 确诊了两例Rubinstein-Taybi综合征患儿,丰富了人类CREBBP基因突变数据库.

Objective To summarize the clinical characteristics and identify gene mutations of 2 probands with Rubinstein-Taybi syndrome(RSTS).Methods Clinical characteristics of 2 probands with Rubinstein-Taybi syndrome were summarized.Genomic DNA was extracted from peripheral blood samples from the patients and their parents.Genomic DNA was subjected to whole exome next generation sequencing.Suspected variants were confirmed by Sanger sequencing.Results The two patients were characterized by typical facial features,broad thumbs and big toes,intellectual disability,and postnatal growth retardation.Two variants of the CREBBP gene,namely c.3779+1G>A and c.5052_c.5053insT,were respectively identified in the 2 patients.Among these,c.3779+1G>A was a previously known pathological mutation,while c.5052_c.5053insT was unreported previously.Both variants were predicted to be pathological.Conclusion Two cases of Rubinstein-Taybi syndrome were diagnosed,which facilitated the diagnosis and genetic counselling.