脑-肺-甲状腺综合征1例患儿的临床及NKX2-1基因变异分析

Analysis of clinical characteristics and variant of NKX2-1 gene in a Chinese boy with Brain-Lung-Thyroid syndrome

目的分析1例脑-肺-甲状腺综合征患儿的遗传学病因。方法以2022年5月27日就诊于山东大学附属儿童医院的1例患儿作为研究对象。采集患儿的临床信息,对患儿及其父母进行家系全外显子组测序,用Sanger测序对候选变异进行验证,在确诊后对患儿进行个体化治疗。结果患儿为2岁7月龄男性,表现为全面发育落后、共济失调、甲状腺功能减退。基因测序显示其携带NKX2-1基因c.674C>T新发杂合变异。患儿被确诊为脑-肺-甲状腺综合征。胸部CT检查提示肺间实质病变,经布地奈德雾化吸入后有所减轻。结论新发现的c.674C>T变异扩大了NKX2-1基因的变异谱。布地奈德气雾剂可用于治疗脑-肺-甲状腺综合征相关的肺部炎症。

ObjectiveTo carry out clinical and genetic analysis for a child featuring Brain-Lung-Thyroid syndrome(BLTS).MethodsA child who had presented at the Children′s Hospital Affiliated to Shandong University on May 27,2022 was selected as the study subject.Clinical data was collected.Trio-whole exome sequencing(Trio-WES)was carried out for the child and his parents,and candidate variant was verified by Sanger sequencing and bioinformatic analysis.The child was given individualized treatment following the diagnosis.ResultsThe child,a two-year-and-seven-month-old boy,had presented with global developmental delay,ataxia and hypothyroidism.WES revealed that he has harbored a heterozygous c.674C>T variant of the NKX2-1 gene,based on which he was diagnosed with BLTS.CT scan revealed interstitial and parenchymal inflammation in his lungs,which was reduced by budesonide aerosol inhalation.ConclusionDiscovery of the novel c.674C>T variant has enriched the mutational spectrum of the NKX2-1 gene.Budesonide aerosol may be used to treat lung inflammation associated with BLTS.