1个CARD11基因变异致NF-κB相关B细胞增殖和T细胞失能性疾病家系的临床特征及遗传学病因分析  

The clinical phenotype and genetic etiology analysis of a B-cell expansion with NF-κB and T cell anergy family with CARD11 gene variation

作　　者：郑吉卡 闫露露[2,3] 薛江阳 李海波 吴菱 陈圆玲[1] 狄亚珍[1] ZHENG Jika;YAN Lulu;XUE Jiangyang;LI Haibo;WU Ling;CHEN Yuanling;DI Yazhen(Department of Pediatrics,Ningbo Women and Children's Hospital,Women and Children's Hospital of Ningbo University,Ningbo,Zhejiang 315012,China;The Central Laboratory of Birth Defects Prevention and Control,Ningbo Women and Children's Hospital,Ningbo,Zhejiang 315012,China;Ningbo Key Laboratory of Fetal Diseases,Ningbo,Zhejiang 315012,China)

机构地区：[1]宁波市妇女儿童医院/宁波大学附属妇女儿童医院儿科,浙江宁波315012 [2]宁波市妇女儿童医院出生缺陷综合防治中心,浙江宁波315012 [3]宁波市胎儿源性疾病重点实验室,浙江宁波315012

出　　处：《中国优生与遗传杂志》2024年第5期979-985,共7页Chinese Journal of Birth Health & Heredity

基　　金：宁波市医疗卫生高端团队重大攻坚项目(2022020405)。

摘　　要：目的探讨1个NF-κB相关B细胞增殖和T细胞失能性疾病(BENTA)家系遗传学病因,总结其临床特征与基因变异的特点。方法选取2022年3月3日就诊于宁波市妇女儿童医院的1个BENTA家系作为研究对象,收集该家系患者的临床资料,进行全外显子组测序(WES),对候选的基因变异进行Sanger测序验证,并进行系统的文献综述。结果患儿表现为淋巴结大、脾大、反复呼吸道感染、关节痛、皮肤紫癜等。其父亲脾大,多处淋巴结大,易呼吸道感染。WES检测提示患儿携带CARD11基因杂合变异c.368G>A(p.Gly123Asp),Sanger测序验证证实该变异遗传自父亲,致病变异在家系中共分离。根据美国医学遗传学与基因组学学会(ACMG)相关指南,c.368G>A评级为疑似致病性变异(PS2+PM2_Supporting+PM5)。结论CARD11基因的c.368G>A(p.Gly123Asp)变异可能是患儿及其父亲的遗传学病因。上述发现丰富了CARD11基因的表型谱。临床上有B淋巴细胞增多、脾大、反复呼吸道感染的患者需警惕BENTA病,进行基因检测确诊。Objective To investigate the genetic etiology of a BENTA(B-cell expansion with NF-κB and T cell anergy)family line and to summarize its clinical characteristics and gene variants.Methods A BENTA family line attending Ningbo Women and Children's Hospital on 3 March 2022 was chosen as the research subject,and the clinical data of the patients in this family line were collected.Furthermore,whole exome sequencing(WES)and Sanger sequencing were performed to validate the candidate gene variants for completion of a systematic literature review.Results The child exhibited large lymph nodes,splenomegaly,recurrent respiratory infections,arthralgia,and cutaneous purpura.His father suffered from splenomegaly,numerous lymph nodes,and respiratory infections.WES revealed c.368G>A(p.Gly123Asp),which is a heterozygous variant of the CARD11 gene,and Sanger sequencing confirmed that the variant was inherited from his father.The pathogenic mutation was isolated in the family.According to the American College of Medical Genetics and Genomics guidelines,c.368G>A was rated as a suspected pathogenic variant(PS2+PM2_Supporting+PM5).Conclusion The c.368G>A(p.Gly123Asp)variant of the CARD11 gene may be the genetic cause of the disease occurring to the children and their fathers.The above findings enrich the phenotypic spectrum of the CARD11 gene.The patients exhibiting clinical B-lymphocytosis,splenomegaly,and recurrent respiratory infections should be aware of BENTA disease and undergo genetic test to confirm the diagnosis.

关 键 词：CARD11基因 NF-κB相关B细胞增殖和T细胞失能性疾病 全外显子组测序 B淋巴细胞增多 

分 类 号：R725[医药卫生—儿科]