PQBP1基因c.586C>T变异导致Renpenning综合征的临床特点和遗传学分析  

Clinical characteristics and genetic analysis of Renpenning syndrome caused by c.586C>T variation in PQBP1 gene

作　　者：余艳红 欧阳秋星 李宏 卢静钿 张谞卓 叶夏 裘娟 李颖 YU Yanhong;OUYANG Qiuxing;LI Hong;LU Jingtian;ZHANG Xuzhuo;YE Xia;QIU Juan;LI Ying(Center of Prenatal Diagnosis,Maternal and Child Health Care Hospital of Longhua District,Guangdong 518109,China;Center of Children's Rehabilitation,Maternal and Child Health Care Hospital of Longhua District,Guangdong 518109,China;No3 Obstetrical Ward Maternal and Child Health Care Hospital of Longhua District,Guangdong 518109,China)

机构地区：[1]深圳市龙华区妇幼保健院产前诊断中心,广东深圳518109 [2]深圳市龙华区妇幼保健院儿童康复中心,广东深圳518109 [3]深圳市龙华区妇幼保健院妇产科产三病区,广东深圳518109

出　　处：《中国优生与遗传杂志》2024年第5期1012-1017,共6页Chinese Journal of Birth Health & Heredity

摘　　要：目的探讨1例不明原因导致混合型发育障碍患儿的临床表型和遗传学特征,为该患儿病因明确、遗传咨询及家庭再生育提供可靠理论依据。方法回顾分析2023年1月因“3岁3个月不会说话,主动社交差,头围小”,来深圳市龙华区妇幼保健院儿童康复科就诊患儿的病史和家族史,采集患儿的临床数据资料,对患儿及父母外周血进行G显带核型分析,对患儿脆性X染色体综合征(FXS)相关基因FMR1进行检测,采用全外显子组测序(WES)对患儿进行遗传学分析,Sanger测序对候选变异进行家系验证来源,根据美国医学遗传学与基因组学学会(ACMG)相关指南,利用生物信息学软件对候选变异进行致病性评级。回顾复习相关报道文献,归纳PQBP1变异所致Renpenning综合征病例的临床特点以及遗传学特征。结果患儿及其父母G显带核型分析结果正常,FXS相关基因FMR1未检测到异常扩增。WES提示患儿携带PQBP1基因半合子变异:c.586C>T(p.Arg196Ter),此变异使得PQBP1第196号氨基酸由精氨酸变成终止密码子,导致终止密码子提前。根据《ACMG遗传变异分类标准与指南》,该变异评级为“致病性变异”。迄今为止,国内外已报道了16种PQBP1基因变异类型,国内尚未见c.586C>T位点变异所致病例报道,患者携带不同类型变异,通常具有差异的表型。结论该患儿混合型发育障碍由PQBP1基因c.586C>T突变导致Renpenning综合征造成,本研究提高了临床对该疾病的认识,对合理评估患儿预后及家庭再生育具有重要指导意义。Objective To conduct a comprehensive analysis of the clinical and genetic characteristics associated with an undetermined cause-induced mixed developmental disorder case,aiming to establish a robust theoretical foundation for understanding the etiology of the child,facilitating genetic counseling,and guiding family reproduction.Methods The medical and family history of the patient who presented to the Children's Rehabilitation Department of Maternal and Child Health Care Hospital of Longhua District in Shenzhen on January,2023,due to“inability to speak at the age of 3 years and 3 months,poor active social interaction,and small head circumference”were collected,followed by a comprehensive clinical examination.Peripheral blood G-banding karyotype analysis was performed on both the children and their parents.Detection of FMR1gene associated with Fragile X syndrome(FXS)was conducted in children.Whole exome sequencing(WES),Sanger sequencing for pedigree verification of candidate variants,as well as bioinformatics software utilization to assess pathogenicity according to relevant guidelines from the American Society for Medical Genetics and Genomics(ACMG).A review was conducted on the clinical and genetic characteristics of Renpenning syndrome caused by PQBP1 variation.Results The G-banded karyotype analysis revealed no abnormalities in both the children and their parents.No abnormal amplification of FXS-related gene FMR1 was detected either.WES indicated that the patients carried PQBP1 hemizygous variation:C.586C>T(p.Arg196Ter),leading to amino acid No.196 changing from arginine to a stop codon.Which was classified as“pathogenic mutation”based on ACMG Classification Standards and Guidelines for Genetic Variation.So far,16 types of PQBP1 mutation have been reported,and no case caused by c.586C>T mutation has been reported in China.Different mutation types usually have different phenotypes.Conclusion Whole exome sequencing revealed that this case of mixed global growth retardation is caused by Renpenning syndrom

关 键 词：PQBP1基因 Renpenning综合征 混合型全面发育迟缓 全外显子组测序 

分 类 号：R749.94[医药卫生—神经病学与精神病学]