ATRX基因变异所致新生儿X连锁α-地中海贫血伴精神发育迟滞综合征1例临床特征与遗传学分析并文献复习  

Clinical feature and genetic analysis of a case of X-linked alpha-thalassemia mental retardation syndrome neonate caused by ATRX gene variant and literature review

作　　者：徐千雅[1] 程欣茹[1] 张姗姗[1] 蔡奥捷 张茜[1] Xu Qianya;Cheng Xinru;Zhang Shanshan;Cai Aojie;Zhang Qian(Department of Neonatology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450000,China)

机构地区：[1]郑州大学第一附属医院新生儿科,郑州450000

出　　处：《中华医学遗传学杂志》2025年第2期162-169,共8页Chinese Journal of Medical Genetics

基　　金：河南省医学科技攻关计划联合共建项目(LHGJ20230224)。

摘　　要：目的探讨1例ATRX基因变异所致X连锁α-地中海贫血伴精神发育迟滞综合征(ATR-X)新生儿的临床表型特征与遗传学病因,并对ATRX基因变异所致ATR-X患儿相关文献进行复习。方法选择2022年2月11日,因"生后反应迟钝、呻吟、皮肤发绀30 min",于出生医院新生儿科治疗4 d效果不佳,转诊至郑州大学第一附属医院治疗的1例ATR-X新生儿作为研究对象。采集本研究患儿及其父母外周血3 mL,提取其基因组DNA进行全外显子组测序(WES),并采用Sanger测序法,对患儿致病基因变异进行家系验证。根据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》,对患儿基因变异位点进行致病性评级,并应用美国通用蛋白质资源数据库(UniProt)对相关变异蛋白进行氨基酸序列保守性分析,应用瑞士在线蛋白三维建模数据库(SWISS-MODEL)等对相关变异蛋白进行可视化分析。分别以"α-地中海贫血伴精神发育迟滞综合征""儿童"""ATRX基因"与"α-thalassemia with mental retardation syndrome""child""ATRX gene"为中、英文关键词,在中国知网、万方数据知识服务平台和PubMed数据中检索ATRX基因变异所致ATR-X患儿相关文献,对检索文献报道的ATR-X患儿临床表型进行分析。检索时限设定为各数据库建库至2023年12月31日。本研究遵循的研究程序经郑州大学第一附属医院伦理委员会的审查(批准号:2023-KY-1360-002),并与患儿监护人签署临床研究知情同意书。结果本研究患儿出生后出现反应迟钝、喂养困难并呕吐、体温偏低、四肢肌力低下、呼吸暂停症状,听力筛查异常,新生儿20项行为神经评分(NBNA)评分为19分(较正常值低),血红蛋白(Hb)电泳实验提示α-地中海贫血。WES和Sanger测序结果显示,本研究患儿ATRX基因第9外显子存在c.668G>A(p.C223Y)半合子错义变异,其父母均未携带该变异,为新发变异。根据ACMG制定的《遗传变异分类标ObjectiveTo explore the clinical phenotype and genetic etiology of a neonate with X-linked alpha-thalassemia mental retardation syndrome(ATR-X)caused by ATRX gene variant,and review relatede literature on children with ATR-X caused by ATRX gene variants.MethodsA case of ATR-X neonate who was transferred to the First Affiliated Hospital of Zhengzhou University on February 11,2022 for poor effect of treatment in the neonatology department of the hospital where he was born for 4 days due to"postnatal slow response,groaning,and cyanosis of the skin for 30 min"was selected as the study subject.3 mL of peripheral blood was collected from the child and their parents,and genomic DNA was extracted for whole exome sequencing(WES).Sanger sequencing was used to verify the pathogenic gene variations in the child′s family.The pathogenicity of genetic variant sites was assessed based on the Standards and Guidelines for the Interpretation of Sequence Variants by American College of Medical Genetics and Genomics(ACMG).The amino acid sequence conservation analysis of relevant variant proteins was conducted by the Universal Protein Resource Database(UniProt)and visual analysis of these variant proteins was performed by Swiss online protein three-dimensional modeling database(SWISS-MODEL).Using keywords such as"ATRX gene"and"X-linked alpha-thalassemia mental retardation syndrome"both in Chinese and English,relevant literature on ATR-X children caused by ATRX gene variants was retrieved from the CNKI,Wangfang Data Knowledge Service Platform,and PubMed databases,and the clinical phenotypes of ATR-X patients reported in the retrieved literature were analyzed.The literature retrieval time was set from the establishment of each database to December 31st,2023.This study followed the research procedures approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University(Ethics No.2023-KY-1360-002),and informed consent of clinical study was signed by the guardian of the child.ResultsThe child in this study presented

关 键 词：Α地中海贫血 精神发育迟滞 X连锁 ATRX基因 遗传变异 儿童 

分 类 号：R722.11[医药卫生—儿科]