5例糖原贮积症Ⅸc型患儿临床和PHKG2基因突变分析  

Clinical features and PHKG 2 gene mutation analysis of 5 Chinese patients with glycogen storage disease Ⅸc

作　　者：周迪禹 房迪[1] 邱文娟[1] 叶军[1] 韩连书[1] 张惠文[1] 余永国[1] 梁黎黎[1] 顾学范[1] ZHOU Diyu;FANG Di;QIU Wenjuan;YE Jun;HAN Lianshu;ZHANG Huiwen;YU Yongguo;LIANG Lili;GU Xuefan(Department of Pediatric Endocrinology/Genetics, Shanghai Institute of Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China)

机构地区：[1]上海交通大学医学院附属新华医院,上海儿科医学研究所内分泌/遗传室,上海200092

出　　处：《临床儿科杂志》2017年第8期609-612,共4页Journal of Clinical Pediatrics

基　　金：国家自然科学基金(No.81170811);上海市卫生局基金(No.20134005);国家重点研发计划精准医学研究专项(No.2016YFC0905100)

摘　　要：目的分析5例糖原贮积症(GSD)Ⅸc型患儿的临床、生化及基因突变特点。方法回顾分析5例GSD Ⅸc型患儿的临床情况,并采用靶向测序技术进行基因分析,Sanger测序验证所发现的PHKG2基因突变及其父母来源。结果5例患儿均表现为明显肝大和矮小,4例有运动耐力差;均有空腹低血糖,肝酶中重度升高,血三酰甘油升高;肝脏超声示无肝硬化。靶向测序发现5例患儿均携带PHKG2基因纯合或复合杂合致病或可能致病突变,发现1种已报道突变p.E157K和5种新突变(p.E56X,p.R185X,c.79_88delins TCTGGTCG,c.761del C,p.R279C),p.E157K为患儿的热点突变(50%)。结论靶向测序有助于确诊GSD Ⅸc型,p.E157K为热点突变。Objective To investigate the clinical,laboratory and genetic features of glycogen storage disease(GSD)IXc.Methods Five patients suspected as liver GSD were included in our study.DNA was extracted from peripheral blood of allthe patients and diagnoses were made after target sequencing to nearly2700disease causing genes.All detected mutations werecon?rmed in the probands and their parents.Further analysis was based on clinical features,routine laboratory examinations andtreatment.Results All the5patients manifested with severe hepatomegaly,hypoglycemia,moderately to severely elevatedliver enzyme levels,hypertriglyceridemia and growth retardation.Four cases showed poor exercise tolerance but with normalcreatine kinase(CK)levels.None of the patients showed liver cirrhosis.Growth velocity and hepatomegaly was improvedafter the uncooked corn starch treatment was initiated.In the5patients,6different pathogenic or likely pathogenic mutationsin the PHKG2gene were identified,including one reported mutation(p.E157K)and five novel mutations(p.E56X,p.R185X,c.79_88delinsTCTGGTCG,c.761delC,p.R279C).The p.E157K was the most frequently mutation identified(6/12,50%).Conclusions The p.E157K mutation is the hot mutation in our small cohort.Main clinical features of our patients includefasting hypoglycemia,impaired liver function,short statures and poor exercise tolerance,without developing liver cirrhosis.

关 键 词：糖原贮积症IXc型 PHKG2基因 靶向测序 突变 

分 类 号：R725.8[医药卫生—儿科]