一例MAP2K1基因新发变异所致的心-面-皮肤综合征患儿的临床分析

Clinical analysis of a child with Cardio-facio-cutaneous syndrome due to a de novo variant of MAP2K1 gene

目的探讨一例由MAP2K1基因变异引起的心-面-皮肤综合征(cardio-facio-cutaneous syndrome,CFCS)患儿基因型与表型的对应关系。方法收集疑似CFCS患儿及其父母的外周血样,提取基因组DNA,对患儿及父母采用全外显子组测序,最后用Sanger测序对可疑变异位点进行验证。结果患儿为男性,具有典型的CFCS面容以及发育迟滞。经全外显子组检测分析发现患儿的MAP2K1基因第3外显子上存在1个新发的杂合错义变异c.389A>G(p.Tyr130Cys),Sanger测序验证了该结果,根据最新美国医学遗传学与基因组学学会评级指南判定为疑似致病性变异。结论患儿临床未发现心脏结构、功能的异常以及癫痫发作,但具有典型面容及皮肤异常,伴有生长发育迟缓、智能障碍、泌尿系统结构异常。该病例丰富了MAP2K1基因变异导致的CFCS表型谱。

Objective To explore the genotype-phenotype correlation of a patient with cardio-facio-cutaneous syndrome(CFCS)due to variant of the MAP2K1 gene.Methods DNA was extracted from peripheral blood samples of the infant and his parents and subjected to whole exome sequencing.Results Candidate variant was verified by Sanger sequencing.The patient had typical CFCS facies and developmental delay,and was found to harbor a de novo heterozygous c.389A>G(p.Tyr130Cys)missense variant in exon 3 of the MAP2K1 gene.Based on the American college of Medical Genetics and Genomics guidelines,this variant was classified as likely pathogenic.Conclusion This patient has differed from previously reported cases by having no cardiac anomaly or seizures but typical facial features and skin abnormalities accompanied by growth retardation,intellectual impairment,and urinary malformation.It has therefore enriched the phenotypic spectrum of CFCS due to variants of the MAP2K1 gene.