NBAS基因变异所致婴儿肝衰竭综合征2型3例患儿的临床及遗传学研究  

Clinical features and genetic analysis of three patients with Infantile liver failure syndrome type 2 due to variants of NBAS gene

作　　者：李素丽[1] 于志丹 郑璇 权冰洁 刘怡静 梅世月 周方 Li Suli;Yu Zhidan;Zheng Xuan;Quan Bingjie;Liu Yijing;Mei Shiyue;Zhou Fang(Department of Digestive Disease,Children′s Hospital Affiliated to Zhengzhou University,Henan Children′s Hospital,Zhengzhou Children′s Hospital,Zhengzhou,Henan 450018,China;Henan Provincial Key Laboratory of Children′s Genetics and Metabolic Diseases,Zhengzhou,Henan 450018,China)

机构地区：[1]郑州大学附属儿童医院、河南省儿童医院、郑州儿童医院消化科,郑州450018 [2]河南省遗传代谢性疾病重点实验室,郑州450018

出　　处：《中华医学遗传学杂志》2025年第1期56-63,共8页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(81903330);河南省科技攻关计划(232102311124);河南省医学科技攻关联合共建项目(LHGJ20220733)。

摘　　要：目的探讨3例婴儿肝衰竭综合征2型(ILFS2)患儿的临床特征及基因变异情况。方法选取3例于2023年2月至2024年2月就诊于郑州大学附属儿童医院的ILFS2患儿作为研究对象。收集患儿的临床资料。采集患儿及其父母的外周血样,对其进行家系全外显子组测序(WES)。用Sanger测序法对3个家系的候选变异进行验证。参考美国医学遗传学与基因组学学会(ACMG)制定的《遗传变异分类标准与指南》,对3例患儿的候选变异的致病性进行评级。本研究通过了郑州大学附属儿童医院医学伦理委员会的审查(批准号:2024-k-069)结果3例患儿均表现为发热相关的反复急性肝衰竭。基因检测提示患儿1存在NBAS基因c.3596G>A与c.1181A>T复合杂合变异;患儿2存在NBAS基因c.2617C>T与c.2T>C复合杂合变异;患儿3存在NBAS基因c.3596G>A和c.2817_2818insT复合杂合变异。检出的3个变异中,c.1181A>T和c.2817_2818insT既往均未见报道。根据ACMG遗传变异解读指南,二者分别被判定为意义不明变异(PM2_Supporting+PM3+PP3)和致病性变异(PVS1+PM2_Supporting+PM3)。结论结合患儿的临床表型,NBAS基因的复合杂合变异可能是3个患儿的遗传学病因。对于不明原因发热相关的急性肝衰竭患儿,需警惕ILFS2的可能性,尽早完善基因检测。早期诊断和及时干预可显著改善预后。c.1181A>T与c.2817_2818insT变异的发现丰富了NBAS基因的变异谱。ObjectiveTo explore the clinical features and genetic characteristics of three patients with Infantile liver failure syndrome type 2(ILFS2).MethodsThree children who were diagnosed with ILFS2 at the Children′s Hospital Affiliated to Zhengzhou University from February 2023 to February 2024 were selected as the study subjects.Clinical data of the children were collected.Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing(WES).Candidate variants of the NBAS gene were verified by Sanger sequencing.This study was approved by the Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University(Ethics No.2024-k-069).ResultsThe three children had presented with fever-triggered recurrent acute liver failure.All of them were found to harbor compound heterozygous variants of the NBAS gene,including c.3596G>A and c.1181A>T in child 1,c.2617C>T and c.2T>C in child 2,and c.3596G>A and c.2817_2818insT in child 3.Among these,the c.1181A>T and c.2817_2818insT variants were unreported previously.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),they were respectively classified as variants of uncertain significance(PM2_Supporting+PM3+PP3)and pathogenic(PVS1+PM2_Supporting+PM3).ConclusionCombined with the patient′s clinical phenotype,the compound heterozygous variants of the NBAS gene probably underlay the pathogenesis of ILFS2 in the three children.For children with fever-related acute liver failure of unknown causes,the possibility of this disease should be suspected,and genetic testing may facilitate the diagnosis.Early diagnosis and timely intervention can significantly improve the prognosis.Discoveries of the c.1181A>T and c.2817_2818insT variants have enriched the mutational spectrum of the NBAS gene.

关 键 词：婴儿肝衰竭综合征2型 NBAS基因 变异 

分 类 号：R725.7[医药卫生—儿科]