ANKRD11基因新变异所致KBG综合征患儿3例的临床及遗传学分析

Clinical and genetic analysis of three children with KBG syndrome due to novel variants of ANKRD11 gene

目的探讨3例KBG综合征患儿的临床与遗传学特征。方法选取2019年10月至2020年9月于郑州大学第一附属医院就诊的3例KBG患儿为研究对象。收集2个家系3例患儿及其家系成员的临床资料,并进行家系全外显子组测序(trio-WES)和Sanger测序。结果3例患儿均有喂养困难、先天性心脏缺陷和特殊面容等表现。家系1中的2例患儿均检出ANKRD11基因c.6270delT(p.Q2091Rfs*84)新发杂合变异;家系2中的1例患儿检出ANKRD11基因c.6858delC(p.D2286Efs*51)新发杂合变异,遗传自具有轻微临床表型的母亲。结论ANKRD11基因移码变异可能是3例KBG综合征患儿的遗传学病因。上述发现丰富了ANKRD11基因的变异谱。

Objective To explore the clinical and genetic characteristics of three children with KBG syndrome.Methods Clinical data of the three children from two families who have presented at the First Affiliated Hospital of Zhengzhou University between October 2019 and September 2020 and their family members were collected.Trio-whole exome sequencing(trio-WES)and Sanger sequencing were carried out.Results All children had feeding difficulties,congenital heart defects and facial dysmorphism.The sib pair from family 1 was found to harbor a novel de novo heterozygous c.6270delT(p.Q2091Rfs*84)variant of the ANKRD11 gene,whilst the child from family 2 was found to harbor a novel heterozygous c.6858delC(p.D2286Efs*51)variant of the ANKRD11 gene which was inherited from his mother who had a mild clinical phenotype.Conclusion The heterozygous frameshift variants of the ANKRD11 gene probably underlay the disease in the three children.Above findings have enriched the spectrum of the ANKRD11 gene variants.