B细胞阴性严重联合免疫缺陷患儿1例的临床表型及RAG1基因变异分析

Analysis of clinical phenotype and variant of RAG1 gene in a child with B-cell-negative Severe Combined Immunodeficiency

目的报道1例以暴发性心肌炎为临床表现的B细胞阴性严重联合免疫缺陷(B-SCID)患儿,并对其进行基因变异分析。方法选取2021年1月31日就诊于福建省妇幼保健院的B-SCID患儿1例为研究对象。对患儿及其父母进行全外显子组测序,并通过Sanger测序对候选变异进行家系验证。结果患儿为女性,2个月11天,出生后反复发生皮肤及肺部感染,此次因合并暴发性心肌炎入院,实验室检查提示IgG降低,外周血T淋巴细胞、B淋巴细胞、NK细胞严重缺乏。全外显子组测序结果提示患儿存在RAG1基因c.C3007T(p.Q1003X)纯合无义变异,患儿父母均为携带者,该变异既往未见报道,根据ACMG相关标准判断为疑似致病。结论确诊了1例RAG1基因变异相关的B-SCID,丰富了RAG1基因的变异谱,同时为患儿家庭的遗传咨询提供了线索。

IObjectiveTo report on a child with B-cell-negative severe combined immunodeficiency(B-SCID)manifesting as fulminant myocarditis and carry out genetic testing for her.MethodssAchildwith B-SCID who presented at Fujian Maternity and Child Health Care Hospital on January 31,2021 was selected as the subject.Whole exome sequencing was carried out for her.Candidate variant was verified by Sanger sequencing.Results The female infant had developed recurrent skin and lung infections soon after birth,and was admitted due to fulminant myocarditis.Serological examination has disclosed a remarkable reduction in immunoglobulins.Flow cytometric analysis revealed that her peripheral blood T and B lymphocytes and NK cells were significantly reduced.Whole exome sequencing revealed that she has harbored a homozygous c.C3007T(p.Q1003X)nonsense variant of the RAG1 gene,for which both of her parents were heterozygous carriers.The variant has not been recorded in normal population databases.Based on guidelines from the American College of Medical Genetics and Genomics,the variant was predicted to be pathogenic.Conclusion A case of RAGl gene associated B-SCID has been diagnosed.Above finding has enriched the spectrum of RAGl gene variants and enabled early diagnosis and intervention of the disease.