EP300基因变异致Rubinstein-Taybi综合征1例

A case of Rubinstein-Taybi syndrome caused by a variant of EP300 gene

目的探讨1例Rubinstein-Taybi综合征(RSTS)患儿的临床特征与遗传学病因。方法选取2021年10月3日于苏州大学附属儿童医院内分泌遗传代谢科就诊的1例RSTS患儿为研究对象。收集患儿的临床资料,采集患儿及其父母的外周静脉血样,对患儿进行全外显子组测序(WES),用Sanger测序对候选变异进行家系验证,并对其进行致病性分析。结果患儿为9岁4个月男性,主要表现为特殊面容、小头畸形、大脚趾宽大、生长发育迟缓以及智力缺陷。WES检测结果显示患儿EP300基因第20外显子存在c.3604G>T(p.E1202*)杂合变异,Sanger测序结果显示,患儿父母该位点为正常基因型,提示为新发变异。EP300基因c.3604G>T(p.E1202*)变异在神州基因组数据云、ExAC、1000 Genomes及gnomAD等数据库中均未见收录;经SIFT、PolyPhen-2及CADD等在线软件对该变异有害性分析结果显示,该变异均被预测为有害性变异。根据美国医学遗传学与基因组学学会变异相关指南,对该变异评级为致病性变异(PVS1+PS2+PM2_Supporting)。结论EP300基因c.3604G>T杂合变异可能是RSTS患儿的遗传学病因,患儿被诊断为RSTS 2型。上述发现进一步丰富了EP300基因的变异谱。

Objective To explore the clinical characteristics and genetic etiology of a child with Rubinstein-Taybi syndrome(RSTS).Methods A child who was admitted to the Children′s Hospital of Soochow University on October 3,2021 was selected as the study subject.Clinical data of the child was collected.Peripheral blood samples of the child and his parents were collected.The child was subjected to whole exome sequencing(WES),and candidate variant was verified by Sanger sequencing of his family members and bioinformatic analysis.Results The patient,a 9-year-and-4-month-old boy,had manifested unique facies,microcephaly,broad toes,growth retardation,and intellectual impairment.WES revealed that he has harbored a heterozygous c.3604G>T(p.E1202*)variant in exon 20 of the EP300 gene.Sanger sequencing confirmed that neither of his parents has carried the same variant.The variant was not found in the Shenzhou Genome data Cloud,ExAC,1000 Genomes and gnomAD databases.Analysis with SIFT,PolyPhen-2 and CADD online software has predicted the variant to be harmful.Based on the guidelines formulated by the American College of Medical Genetics and Genomics,the variant was rated as pathogenic(PVS1+PS2+PM2_Supporting).Conclusion The heterozygous c.3604G>T variant of the EP300 gene probably underlay the RSTS type 2 in this child.Above finding has expanded the variation spectrum of the EP300 gene.