不明原因新生儿脑病的遗传学病因  

Genetic analysis of unexplained neonatal encephalopathy

作　　者：谢晶晶 彭小明[1] 高喜容[1] 李贵南[1] 黄瑞文[1] 庄严[1] 张帆[1] 黄维清 李军帅 张榕[1] Xie Jingjing;Peng Xiaoming;Gao Xirong;Li Guinan;Huang Ruiwen;Zhuang Yan;Zhang Fan;Huang Weiqing;Li Junshuai;Zhang Rong(Department of Neonatology,Children's Hospital of Hunan Province,Changsha 410007,China)

机构地区：[1]湖南省儿童医院新生儿科,长沙410007

出　　处：《中华围产医学杂志》2023年第2期127-133,共7页Chinese Journal of Perinatal Medicine

基　　金：湖南省自然科学基金(2021JJ40278)。

摘　　要：目的探讨不明原因新生儿脑病的遗传学病因。方法回顾性分析2019年1月至2021年5月收住湖南省儿童医院新生儿科、诊断为不明原因新生儿脑病且完善遗传学检测的113例患儿的围产期资料、临床表现、脑电图及头颅MRI表现, 以及遗传检测结果和转归等。用t或χ^(2)检验对数据做统计学分析。结果 113例患儿中, 男性74例(65.5%), 出生胎龄(38.6±1.5)周, 出生体重(2 957±561)g。临床表现以意识障碍最常见(83/113, 73.5%), 其次为惊厥发作(39/113, 34.5%)。38.2%(34/89)头颅MRI异常, 80.4%(74/92)脑电图结果异常。113例患儿中遗传学检测结果异常60例(53.1%), 包括单核苷酸变异48例, 拷贝数变异8例, 染色体变异4例。48例单核苷酸变异可分为综合征类(18例, 37.5%)、代谢类(16例, 33.3%)、癫痫类(11例, 22.9%)和线粒体类(3例, 6.3%), 其中14例基因暂未收录于数据库。至2021年12月31日, 共随访成功103例, 其中75例(72.8%)预后不良, 包括52例(50.5%)死亡, 23例(22.3%)发育迟滞。预后不良患儿的出生体重和惊厥发作比例均低于非预后不良患儿[(2 876±536)与(3 254±554)g, t=3.15;29.3%(22/75)与53.6%(15/28), χ^(2)=5.20], 意识障碍比例高于非预后不良患儿[80.0%(60/75)与53.6%(15/28), χ^(2)=7.19](P值均<0.05)。预后不良患儿的遗传学异常比例与非预后不良患儿相比, 显现出升高的趋势, 但差异未见统计学意义[53.3%(40/75)与46.4%(13/28), χ^(2)=0.39, P=0.533]。结论遗传学异常是不明原因新生儿脑病的重要病因之一。单核苷酸变异为最常见遗传学类型, 综合征类、代谢类、癫痫类是常见的单核苷酸变异类型。Objective To explore the potential genetic causes of unexplained neonatal encephalopathy.Methods This retrospective study enrolled 113 infants diagnosed with unexplained neonatal encephalopathy and underwent genetic testing in the Children's Hospital of Hunan Province from January 2019 to May 2021.Perinatal data,clinical manifestations,electroencephalograph,brain MRI findings,genetic information,and prognosis of those patients were analyzed.T-test or Chi-square test were used for data analysis.Results Of the 113 infants enrolled,74(65.5%)were males.The gestational age at birth was(38.6±1.5)weeks,and the birth weight was(2957±561)g.The most common clinical manifestation was the disturbance of consciousness(83/113,73.5%),followed by seizures(39/113,34.5%).There were 38.2%(34/89)of the patients with abnormal brain MRI,and 80.4%(74/92)presented abnormal electroencephalography.Among the 113 infants,60(53.1%)had genetic abnormalities,including 48 with single nucleotide variations,eight with copy number variations,and four with chromosome abnormalities.Single nucleotide variations in the 48 patients were classified into syndromic(n=18,37.5%),metabolic(n=16,33.3%),epileptic(n=11,22.9%)and mitochondrial-related genes(n=3,6.3%),of which 14 were not included in any database.Among the 103 cases which were successfully followed up until December 31,2021,75(72.8%)had a poor prognosis,including 52(50.5%)death cases and 23(22.3%)cases of development retardation.Birth weight and the incidence of seizures in the poor prognosis group were both lower than those in the non-poor prognosis group[(2876±536)vs(3254±554)g,t=3.15;29.3%(22/75)vs 53.6%(15/28),χ^(2)=5.20;both P<0.05],while the incidence of disturbance of consciousness was higher[80.0%(60/75)vs 53.6%(15/28),χ^(2)=7.19,P<0.05].The proportion of infants with genetic abnormalities in the poor prognosis group was higher than that in the non-poor prognosis group,but the difference was not statistically significant[53.3%(40/75)vs 46.4%(13/28),χ^(2)=0.39,P=0.533].Conclusions G

关 键 词：脑疾病 意识障碍 癫痫 全外显子组测序 多态性 单核苷酸 婴儿 新生 

分 类 号：R722.1[医药卫生—儿科]