摘要
目的探讨一个Bainbridge-Ropers综合征(Bainbridge-Ropers syndrome,BRPS)患儿的临床表型和遗传学特征。方法回顾分析患儿的临床资料,分别应用低深度高通量全基因组拷贝数变异测序(copy number variation sequencing,CNV-seq)和家系全外显子组测序(trio-whole exome sequencing,trio-WES)技术进行遗传学分析,对该家系的胎儿进行产前诊断,并总结国内已报道的BRPS患儿的表型和遗传学特征。结果患儿为男性,6岁,表现为出生后喂养困难、特殊面容、全面发育迟缓和智力障碍,康复治疗效果不佳。trio-WES检测提示其携带ASXL3基因c.1448dupT(p.T484Nfs*5)杂合致病变异,父母和胎儿均未携带该变异。连同国内既往报道的13例患儿,所有患儿均存在特殊面容、运动和语言发育迟缓,共检出12种ASXL3基因变异,均为新发的功能缺失变异,位于第11和12外显子。结论ASXL3基因c.1448dupT(p.T484Nfs*5)杂合变异为本例BRPS患儿的遗传学病因。对于出生后喂养困难、特殊面容、全面发育迟缓和手部异常的婴幼儿应考虑BRPS,并通过WES确诊。
Objective To explore the clinical features and genetic basis for a child with Bainbridge-Ropers syndrome(BRPS).Methods Clinical data of the child were retrospectively analyzed.Copy number variation sequencing(CNV-seq)and trio-based whole exome sequencing(trio-WES)were carried out.Prenatal diagnosis was provided for a at-risk fetus from the pedigree,and genotype-phenotype correlation was summarized through a literature review.Results The proband,a 6-year-old boy,has presented with feeding difficulties,specific craniofacial features,global developmental delay and intellectual disability,which has not improved after rehabilitation treatment.CNV-seq analysis of the patient showed no obvious abnormalities.A de novo heterozygous truncating variation,c.1448dupT(p.T484Nfs*5),was identified in the ASXL3 gene by trio-WES,which was a previously reported pathogenic variant.So far 14 Chinese patients with BRPS and ASXL3 variants have been reported.All patients have shown specific craniofacial features and delayed motor and speech development,and harbored 12 loss-of-function ASXL3 variants,which were de novo in origin and have clustered in exons 11 and 12 of the ASXL3 gene.Conclusion The heterozygous frameshift c.1448dupT(p.T484Nfs*5)variant of the ASXL3 gene probably underlay the disorder in this patient.BRPS should be considered in infants with feeding difficulties,special craniofacial features,global developmental delay and hand anomalies,and WES can help to delineate the pathogenesis and establish the definite diagnosis.
作者
李晶晶
徐菁晗
佘明聪
时盼来
孔祥东
王莉
Li Jingjing;Xu Jinghan;She Mingcong;Shi Panlai;Kong Xiangdong;Wang Li(Genetic and Prenatal Diagnosis Center,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China;Department of Gynecology,the People′s Hospital of Kaifeng,Kaifeng,Henan 475002,China)
出处
《中华医学遗传学杂志》
CAS
CSCD
2022年第11期1228-1232,共5页
Chinese Journal of Medical Genetics
基金
国家重点研发计划(2018YFC1002203)。
