两个Bainbridge-Ropers综合征家系的临床表型及基因变异分析

Analysis of clinical feature and genetic variants in two Chinese pedigrees affected with Bainbridge-Ropers syndrome

目的对2个不相关的精神运动发育迟缓、面容异常的患儿进行临床和基因变异分析,探讨临床表型和基因型的相关性,为家系遗传咨询提供依据。方法收集2个家系成员的临床资料和家族史,采用全外显子组测序分析患儿致病基因,确定可疑变异位点后对家系成员行Sanger测序验证。结果两例患儿临床均表现为运动和语言发育迟缓、体格增长缓慢、面容异常,基因分析结果显示家系1患儿携带ASXL3基因c.3096dup(p.P1033Tfs*2)杂合新发变异,家系2患儿携带ASXL3基因c.3253G>T(p.G1085*)杂合新发变异,且这两个变异均未见既往研究报道。结合两个家系患儿的临床表型和基因检测结果,推测这两名患儿均为ASXL3基因致病变异导致的Bainbridge-Ropers综合征。结论报道了两个Bainbridge-Ropers综合征家系,丰富了中国BRS患者的表型谱和突变谱,明确了患儿的遗传学病因,为家系的产前诊断提供了依据。

Objective To analyze the clinical features and genetic variants in two unrelated patients with psychomotor retardation and facial abnormalities,and to explore their genotype-phenotype correlation.Methods Clinical data and family history of the two pedigrees were collected.Whole exome sequencing(WES)and Sanger sequencing were carried out to detect the potential variants.Results Both patients had presented with mental and language retardation,along with growth delay and facial anomalies.They were both found to harbor de novo loss-of-function variants in exon 12 of the ASXL3 gene,namely c.3096dup(p.Pro1033Thrfs*2)and c.3253G>T(p.Gly1085*).Neither variant was reported previously.Combined with their clinical features and genetic finding,both patients were diagnosed with Bainbridge-Ropes syndrome due to pathogenic variants of the ASXL3 gene.Conclusion Diagnosis of Bainbridge-Ropes syndrome in the two pedigrees has enriched the genotypic and phenotypic spectrum of this disorder and enabled genetic counseling for them.