产前诊断Rubinstein-Taybi综合征胎儿1例

Prenatal diagnosis of a fetus with Rubinstein-Taybi syndrome

目的探讨1例Rubinstein-Taybi综合征(RSTS)胎儿的临床特点及CREBBP基因的变异。方法选取2022年8月在郑州大学第三附属医院确诊的1例RSTS胎儿作为研究对象。收集胎儿的临床资料,对其羊水样本及父母的外周血样本进行家系全外显子测序(WES),对候选变异进行Sanger测序验证。结果产前超声检查发现胎儿足部畸形、小脑蚓部发育不全、脑发育不全、轴前多/并趾畸形。WES检测发现胎儿CREBBP基因(NM_004380.3)第28外显子存在c.4684G>T(p.E1562*)新发杂合变异,既往未见报道。根据美国医学遗传学与基因组学学会(ACMG)相关指南判定为致病性(PVS1+PS2_Moderate+PM2_Supporting)。胎儿父母在遗传咨询后选择引产,但拒绝对胎儿进行尸检。结论CREBBP基因变异可能是本研究RSTS胎儿的遗传学病因。c.4684G>T(p.E1562*)变异的发现拓宽了CREBBP基因的变异谱,同时证实WES是产前诊断RSTS的有效方法。

ObjectiveTo explore the clinical characteristics and variant of CREBBP gene in a fetus with Rubinstein-Taybi syndrome(RSTS).MethodsA fetus with RSTS diagnosed at the Third Affiliated Hospital of Zhengzhou University in August 2022 was selected as the study subject.Clinical data,amniotic fluid sample of the fetus and peripheral blood samples of its parents were collected for whole exome sequencing(WES).Candidate variant was verified by Sanger sequencing.ResultsFoot malformation,cerebellar vermis agenesis,brain agenesis,polysyndactyly of the big toes and other phenotypes were found by prenatal ultrasound.WES revealed that the fetus has harbored a heterozygous c.4684G>T(p.E1562*)variant in exon 28 of the CREBBP gene(NM_004380.3),which was de novo in origin.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),the variant was predicted to be pathogenic(PVS1+PS2_Moderate+PM2_Supporting).After genetic counseling,the couple had opted to terminate the pregnancy and refused autopsy for the fetus.ConclusionThe c.4684G>T(p.E1562*)variant of the CREBBP gene probably underlay the RSTS in this fetus.The newly discovered variant has enriched the mutational spectrum of the CREBBP gene and illustrated that WES is an efficient tool for the prenatal diagnosis of RSTS.