摘要
目的总结Rubinstein-Taybi综合征(RSTS)的基因变异类型和临床表型特点,探讨其基因型与表型的相关性。方法病例系列研究,收集2013年1月至2022年7月就诊于首都儿科研究所附属儿童医院,通过全外显子测序或染色体芯片、拷贝数变异测序,检出CREBBP或EP300基因变异的21例RSTS患儿的病例资料。总结其基因变异类型并回访其表型数目。根据变异类型将患儿分别分为点变异或拷贝数缺失组、EP300基因或CREBBP基因变异组、功能丧失或错义变异组。组间表型数目比较采用两独立样本秩和检验。结果21例患儿中男12例、女9例,年龄范围为1月龄至14岁2月龄,14例(67%)点变异,7例(33%)拷贝数缺失;其中20例(95%)为新生变异。20例患儿随访获得详细表型数目,95%(19/20)在2岁以内出现神经发育迟缓,80%(16/20)具有特殊面容。组间表型数目比较,点变异组(14例)与拷贝数缺失变异组(6例)[5.0(3.0,7.0)比5.0(2.5,5.3)个,Z=0.75,P=0.452];CREBBP基因组(10例)与EP300基因变异组(4例)[5.0(3.8,7.0)比4.0(2.0,6.0)个,Z=1.14,P=0.253];功能丧失变异组(9例)与错义变异组(5例)[6.0(4.5,7.0)比3.0(2.5,5.5)个,Z=1.54,P=0.121],差异均无统计学意义。结论RSTS患儿主要临床表型为神经发育迟缓,特定面容为疑似患者寻求基因检测提供依据。基因变异类型和表型数目无关。
Objective To investigate the phenotypes of Rubinstein-Taybi syndrome(RSTS)caused by variants in the CREBBP or EP300 gene,and the correlation between genotype and phenotype.Methods This case series study was performed on pediatric patients who were referred to the Children′s Hospital of Capital Institute of Pediatrics between January 2013 and July 2022.Both point variant and copy number deletion in CREBBP or EP300 gene were detected by whole exome sequencing,chromosomal microarray analysis,or copy number variation sequencing(CNV-seq).The variant categories were summarized and phenotype numbers were re-visited for RSTS patients.Based on variant types,the patients were divided into different groups(point variant or copy number deletion,EP300 or CREBBP point variant,and loss of function or missense variant).Phenotype counts between different groups were compared using the rank-sum test of two independent samples.Results A total of 21 RSTS patients were recruited,including 12 males and 9 females,with ages ranging from 1 month to 14 years and 2 months.Among them,67%(14/21)had point variants,and 33%(7/21)had copy number deletions.Out of these,20 variants(95%)were de novo.Among 20 patients finishing phenotype count during re-visit,95%(19/20)of the patients exhibited developmental delays before the age of 2 years.Additionally,80%(16/20)of the patients had distinctive facial features.Considering phenotype count,no statistically significant difference was found between point variant(14 cases)and copy number deletion(6 cases)(5.0(3.0,7.0)vs.5.0(2.5,5.3),Z=0.75,P=0.452),CREBBP(10 cases)and EP300 gene(4 cases)point variant(5.0(3.8,7.0)vs.4.0(2.0,6.0),Z=1.14,P=0.253),and loss of function(9 cases)and missense(5 cases)variant(6.0(4.5,7.0)vs.3.0(2.5,5.5),Z=1.54,P=0.121).Conclusions Patients with RSTS primarily exhibit developmental delays in early childhood.Specific facial features serve as suggested signs of genetic testing.However,no significant genotype-phenotype correlation is found.
作者
杨圣海
刘浩然
李佳一
张裕
刘子勤
王琳
陈晓丽
上官少方
Yang Shenghai;Liu Haoran;Li Jiayi;Zhang Yu;Liu Ziqin;Wang Lin;Chen Xiaoli;Shangguan Shaofang(Department of Neurology,Children′s Hospital of Capital Institute of Pediatrics,Beijing 100020,China;Department of Genetics,Capital Institute of Pediatrics,Beijing 100020,China;Department of Laboratory Center,Capital Institute of Pediatrics,Beijing 100020,China;Department of Endocrinology,Children′s Hospital of Capital Institute of Pediatrics,Beijing 100020,China;Department of Child Health Care,Children′s Hospital of Capital Institute of Pediatrics,Beijing 100020,China)
出处
《中华儿科杂志》
CAS
CSCD
北大核心
2024年第4期351-356,共6页
Chinese Journal of Pediatrics
基金
首都卫生发展科研专项(2020-2-1131)
北京市医院管理中心“培育计划”(PX2023049)。
