合并围生期缺氧的新生儿脑病遗传因素分析  

Genotype and phenotype analysis of neonates with neonatal encephalopathy complicated with perinatal hypoxic event

作　　者：肖甜甜 杨琳[2] 吴冰冰[2] 彭小敏 王慧君[2] 程国强 王来栓 曹云 胡黎园 周文浩 Xiao Tiantian;Yang Lin;Wu Bingbing;Peng Xiaomin;Wang Huijun;Cheng Guoqiang;Wang Laishuan;Cao Yun;Hu Liyuan;Zhou Wenhao(Department of Neonatology,Children's Hospital of Fudan University,National Children's Medical Center,Shanghai 201102,China;Center of Molecular Medicine,Children's Hospital of Fudan University,National Children's Medical Center,Shanghai 201102,China)

机构地区：[1]国家儿童医学中心复旦大学附属儿科医院新生儿科,上海201102 [2]国家儿童医学中心复旦大学附属儿科医院分子医学中心,上海201102

出　　处：《中华儿科杂志》2021年第4期280-285,共6页Chinese Journal of Pediatrics

基　　金：上海市市级科技重大专项(2017SHZDZX01)。

摘　　要：目的探讨合并围生期缺氧的新生儿脑病遗传因素。方法收集2016年1月至2019年1月参与复旦大学附属儿科医院"新生儿基因组计划"的133例新生儿。纳入标准为诊断为新生儿脑病、合并围生期急性缺氧事件或Apgar评分≤7分的患儿。回顾性分析患儿临床表现、脑电图及头颅影像学表现、基因测序结果和转归等。结果 133例患儿中男77例(57.9%),女56例(42.1%);剖宫产出生56例(42.1%),自然出生77例(57.9%);其中诊断为新生儿缺氧缺血性脑病的患儿68例(51.1%),颅内出血25例(18.8%),遗传学病因的20例(15.0%),败血症(未合并颅内感染)5例(3.8%)。20例二代测序结果阳性的遗传学病因患儿中,19例明确致病性,1例为意义不明;分别为 4例先天性肌病相关变异基因(MTM1基因变异2例、ACTA1基因变异和RYR1基因变异各1例),4例综合征相关变异基因(CHD7基因变异2例、PTN11和NSDHL基因变异各1例),3例代谢性疾病相关变异基因(OTC、MTHFR、ALDH7A1基因变异各1例),2例癫痫性脑病相关变异基因(KCNT1和PACS2基因变异各1例),1例为呼吸中枢相关变异基因(PHOX2B基因变异)以及6例拷贝数致病变异。20例遗传学病因患儿中,8例(40.0%)肌张力减低,7例(35.0%)惊厥,5例(25.0%)合并畸形;20例患儿或家庭均进行遗传咨询,4例患儿死亡,10例患儿放弃治疗出院,6例患儿经过对症支持治疗后症状缓解,出院后进一步制定专科随访计划。结论在合并围生期缺氧的新生儿中,遗传学病因并不少见。先天性肌病、综合征类、代谢性疾病和癫痫性脑病相关变异基因为常见遗传学病因。Objective To explore the underlying genetic causes of neonatal encephalopathy complicated with perinatal asphyxia.Methods From the neonates recruited to the Neonatal Genome Project of Children′s Hospital of Fudan University between January 2016 and January 2019,113 neonates with neonatal encephalopathy and acute peripartum or intrapartum event or Apgar score≤7 were enrolled in this study.The clinical data,laboratory results,the findings of electroencephalograph and magnetic resonance imaging or head ultrasound,and the genetic information were retrospectively analyzed.Results Of the 133 neonates with neonatal encephalopathy and acute peripartum or intrapartum event or Apgar score≤7 scores,77(57.9%)were males,56(42.1%)were female,56(42.1%)were delivered via cesarean section,and 77(57.9%)were born by vaginal delivery.Among these cases,68(51.1%)were diagnosed of hypoxic ischemic encephalopathy,25(18.8%)had intracranial hemorrhage,20(15%)were related to genetic diseases,and 5(3.8%)had sepsis without central nervous infection.A total of 20 cases with positive results by next-generation sequencing test were identified,including 19 cases with pathogenic variations and 1 case with variation of uncertain significance.These 20 cases included 4 cases with congenital myopathy(2 cases of MTM1 gene pathogenic variants,1 case of ACTA1 and 1 case of RYR1 gene pathogenic variants),4 cases with genetic syndrome(2 cases of CHD7 gene pathogenic variants,1 case of PTN11 gene pathogenic variant,and 1 case of NSDHL gene pathogenic variant),3 cases with metabolic disorders(1 case of OTC gene pathogenic variant,1 case of MTHFR gene pathogenic variant,and 1 case of ALDH7A1 gene pathogenic variant),2 cases with epileptic encephalopathy(1 case of KCNT1 and 1 case of PACS2 gene pathogenic variants),1 case with congenital central hypoventilation syndrome(PHOX2B gene pathogenic variant)and 6 cases with copy-number pathogenic variations.Among these 20 cases,8(40.0%)neonates were presented with persistent hypotonia,7(35.0%)neonates with sei

关 键 词：婴儿 新生 缺氧缺血 脑 高通量核苷酸测序 

分 类 号：R722.1[医药卫生—儿科]