NBAS基因变异导致婴儿肝功能衰竭综合征2型1家系的临床及遗传学分析  

Clinical and genetic analysis of a family with NBAS gene variants causing Infantile liver failure syndrome-2

作　　者：张亚华 吴悠 邬珂瑛 李海波 ZHANG Yahua;WU You;WU Keying;LI Haibo(Department of Infectious Diseases,Women and Children’s Hospital of Ningbo University,Ningbo,Zhejiang 315012,China;Department of Public Health,Women and Children’s Hospital of Ningbo University,Ningbo,Zhejiang 315012,China;Central Laboratory of Birth Defects Prevention and Control,Women and Children’s Hospital of Ningbo University,Ningbo,Zhejiang 315012,China;Ningbo Key Laboratory of Fetal Diseases,Ningbo,Zhejiang 315012,China)

机构地区：[1]宁波大学附属妇女儿童医院感染科,浙江宁波315012 [2]宁波大学附属妇女儿童医院公共卫生科,浙江宁波315012 [3]宁波大学附属妇女儿童医院出生缺陷综合防治实验室,浙江宁波315012 [4]宁波市胚胎源性疾病防治重点实验室,浙江宁波315012

出　　处：《中国优生与遗传杂志》2024年第12期2592-2596,共5页Chinese Journal of Birth Health & Heredity

基　　金：宁波市公益重点项目(2022S035);宁波市医疗卫生高端团队(2022020405);宁波市揭榜挂帅市重点研发计划项目(2023Z178)。

摘　　要：目的揭示NBAS基因缺陷导致的遗传学病因,为疾病的遗传咨询和治疗提供依据。方法选取2023年9月于宁波大学附属妇女儿童医院就诊的婴儿肝功能衰竭综合征2型(ILFS2)一家系2例患儿为研究对象,收集临床表型及家族史信息。采用全外显子组测序(WES)技术对患儿进行检测,针对可疑变异位点进行Sanger测序验证与致病性分析,并对既往相关研究报道行文献综述分析。结果先证者为13岁4月男性患儿,其妹妹8岁1月龄,2例患儿均有发热时出现肝功能异常、肝衰竭。WES提示2例患儿均存在NBAS基因复合杂合致病变异(c.3596G>A、c.1018G>C),分别来自其父母。2患儿随着年龄增长,未经特殊治疗,兄妹的肝功能均有所好转。结论全外显子组测序揭示出ILFS2的遗传学病因,为遗传咨询和疾病治疗提供了依据。同时NBAS基因c.3596G>A/p.Cys1199Tyr可能是中国NBAS基因缺陷症肝衰患者中特有的常见变异位点。Objective To reveal the genetic etiology caused by NBAS gene defects and provide a basis for genetic counseling and treatment of the disease.Methods Two children from a family with infantile liver failure syndrome-2(ILFS2)who were treated at the Women and Children’s Hospital of Ningbo University in September 2023 were selected as research objects.Clinical phenotype and family history information were collected.Whole exome sequencing(WES)technology was used to detect the children.Sanger sequencing verification and pathogenicity analysis were performed on suspicious variant loci,and a literature review and analysis of previous related research reports were conducted.Results The probant is a 13 years and 4 months old male child,and his sister is 8 years and 1 month old.Both children have abnormal liver function and liver failure when they have a fever.WES suggests that both children have compound heterozygous pathogenic variants(C.3596G>A,C.1018G>C)in the NBAS gene,which are inherited from their parents respectively.As the two children grow older,without special treatment,the liver function of the brother and sister has improved.Conclusion Whole exome sequencing reveals the genetic etiology of ILFS2 and provides the basis for genetic counseling and disease treatment.At the same time,the NBAS gene c.3596G>A/p.Cys1199Tyr may be a unique common variant locus in Chinese patients with NBAS gene defect liver failure.

关 键 词：婴儿肝功能衰竭综合征2型 NBAS基因 全外显子组测序 

分 类 号：R725.7[医药卫生—儿科]