先天性糖基化障碍Ⅰa型伴反复呼吸道感染一家系分析并文献复习  

Congenital disorder of glycosylation typeⅠa with recurrent respiratory infections:a family analysis and literature review

作　　者：张振坤[1] 谢振华 刘菁 肖梦君 李娴 张强[1] 张耀东 王海军[2] 李东晓 ZHANG Zhenkun;XIE Zhenhua;LIU Jing;XIAO Mengjun;LI Xian;ZHANG Qiang;ZHANG Yaodong;WANG Haijun;LI Dongxiao(Henan Provincial Key Laboratory of Children's Genetic and Metabolic Diseases,Children's Hospital Affiliated to Zheng-zhou University,Zhengzhou 450018,China;Department of Emergency,Children's Hospital Affiliated to Zhengzhou University)

机构地区：[1]郑州大学附属儿童医院,河南省儿科疾病临床研究中心,河南省儿童遗传代谢性疾病重点实验室,郑州450018 [2]郑州大学附属儿童医院东区急诊科

出　　处：《山西医科大学学报》2025年第2期193-199,共7页Journal of Shanxi Medical University

基　　金：国家自然科学基金资助项目(82000850)。

摘　　要：目的 探讨PMM2基因变异相关先天性糖基化障碍(CDG)伴反复呼吸道感染患者的临床及遗传学特征。方法 收集1例PMM2基因变异致先天性糖基化障碍伴反复呼吸道感染患儿的临床资料,对先证者及其家系成员的可疑致病突变片段进行家系成员Sanger测序。以“PMM2-CDG”“congenital disorder of glycosylation typeⅠa”“先天性糖基化障碍”或“PMM2基因”为关键词,分别检索PubMed数据库、中国知网、万方数据库收录的文献,总结PMM2基因变异所致CDG患者的临床表型、影像学及遗传学特点。结果 患儿,男,3岁,主要表现为语言及运动发育落后、眼球震颤、双眼内斜视、双下肢肌张力高,伴反复呼吸道感染。头颅MRI(2岁11月龄)结果示后颅窝囊性病变,小脑下蚓部及半球发育不全。家系全外显子组测序提示先证者PMM2基因存在父源性c.385G>A(p.Val129Met)与母源性c.395T>C(p.Ile132Thr)复合杂合变异,诊断为先天性糖基化障碍Ⅰa型(CDG-Ⅰa);姐姐在两个位点均为野生型。共检索到国内相关病例文献15篇26例患者,结合本例患者,共27例。国内CDG-Ⅰa患者的主要临床表现为发育落后(92.6%)、肌张力异常(77.8%)、小脑萎缩/发育不全(63.0%)、眼球内斜视(48.1%)、乳头内陷(33.3%)、臀部脂肪垫(22.2%)、癫痫/抽搐(14.8%)等。3例为PMM2基因纯合变异,24例为PMM2基因复合杂合变异。共包含23个基因变异位点,18种错义变异,4种移码变异及1种剪接变异。结论 PMM2基因致病变异可导致神经系统、心脏和免疫系统等多系统异常,对可疑CDG患者应及时行PMM2基因检测,以尽早明确诊断。Objective To investigate the clinical and genetic characteristics of PMM2 gene⁃related congenital disorder of glycosylation(CDG)with recurrent respiratory infections in patients.Methods Clinical data were collected from a child with congenital disorder of glycosylation typeⅠa with recurrent respiratory infections.The suspected pathogenic mutation fragments of the proband and his family members were subjected to Sanger sequencing.The literature containing the keywords of“PMM2-CDG”“congenital disorder of glyco⁃sylation typeⅠa”“CDG”and/or“PMM2 gene”published in PubMed,China National Knowledge Infrastructure,and Wanfang data⁃base were collected.And together with the literature,the clinical phenotype,imaging,and genetic characteristics of PMM2⁃CDG patients were summarized.Results The 3-year-old male proband presented with delayed speech and motor development,nystagmus,esotropia,and high muscle tension,accompanied by recurrent respiratory tract infections.A brain MRI of the proband at the age of 2 years and 11 months showed cystic lesions of posterior cranial fossa with hypoplasia of the cerebellar inferior vermis and hemisphere.The whole⁃exome sequencing(WES)of the family indicated that the proband had a compound heterozygous variant of paternally derived c.385G>A(p.Val129Met)and maternally derived c.395T>C(p.Ile132Thr)in the PMM2 gene,leading to a diagnosis of congenital disorder of glycosylation typeⅠa(CDG-Ⅰa);and the sister was wild⁃type at both loci.A total of 26 cases in 15 domestic relevant articles and one case in this study were reported.The main clinical features of CDG-Ⅰa patients in China were developmental delay(92.6%),dystonia(77.8%),cerebellar atrophy/hypoplasia(63.0%),esotropia(48.1%),inverted nipples(33.3%),gluteal fat pads(22.2%),epilepsy/convulsions(14.8%),etc.Three cases were homozygous variants of PMM2 gene and 24 cases were compound heterozygous variants.A total of 23 genetic variant loci were involved,including 18 missense variants,four frameshift variants an

关 键 词：PMM2基因 先天性糖基化障碍 呼吸道感染 基因变异 全面发育迟缓 

分 类 号：R725.8[医药卫生—儿科]