婴儿型糖原贮积病Ⅱ型基因型表型相关性分析和出生缺陷预防  

GENOTYPE-PHENOTYPE CORRELATION IN INFANTILE GLYCOGEN STORAGE DISEASE TYPE Ⅱ AND PREVENTION OF BIRTH DEFECT

作　　者：王涛[1] 雷茜[1] 肖红玉 张建芳 王娟莉[1] 刘百灵[3] 许小艳[1] 姚振宇 张艳敏[1,4,5] WANG Tao;LEI Xi;XIAO Hongyu;ZHANG Jianfang;WANG Juanli;LIU Bailing;XU Xiaoyan;YAO Zhenyu;ZHANG Yanmin(Department of Cardiology,the Affiliated Children＇s Hospital of Xi′an Jiaotong University（Xi′an Children＇s Hospital）,Xi′an,710003,China)

机构地区：[1]西安交通大学附属儿童医院(西安市儿童医院)心内科,陕西西安710003 [2]空军军医大学第一附属医院妇产科 [3]西安交通大学附属儿童医院(西安市儿童医院)超声科 [4]陕西省儿科疾病研究所 [5]西安市儿童健康与疾病重点实验室

出　　处：《精准医学杂志》2018年第4期307-310,315,共5页Journal of Precision Medicine

基　　金：国家自然科学基金面上项目(81470452);西安市科技局"科技+"行动计划-医学研究项目(201805098YX6SF32(5))

摘　　要：目的分析伴有肥厚型心肌病的婴儿型糖原贮积病Ⅱ型(GSDⅡ)的基因型和表型特点,以及下一胎出生缺陷的预防方法。方法对2016年12月—2017年5月西安市儿童医院心脏内科住院诊断治疗的4例婴儿型GSDⅡ病儿,进行临床和实验室检查及酸性α-葡萄糖苷酶(GAA)活性测定,采用Sanger直接测序或二代测序法进行GAA基因突变检测,并对2例先证者母亲下一胎胎儿进行产前GAA基因突变筛查。结果 4例病儿分别在生后2~8月龄出现运动发育迟缓、肌无力、心肌肥厚,3例病儿GAA活性分别为2.5、2.1、1.9nmol/(g·min);4例病儿基因检测发现8个GAA基因致病突变,分别为p.R608X、p.L701P、p.R608X、p.E888X、p.W279C、p.N535Qfs*3、p.S601L、p.E888X。病儿均于确诊后3~6个月死亡。2例进行了下一胎产前诊断,其中1例携带单个杂合突变,顺利分娩,1例携带与先证者相同复合杂合突变,终止妊娠。结论发病GSDⅡ病儿分别携带来自父母的致病突变,婴儿型GSDⅡ病儿症状出现早,未经酶替代治疗死亡率高。GSDⅡ在我国尚未列入产前筛查,对于病儿母亲下一胎胎儿进行GAA基因检查,有助于GSDⅡ出生缺陷的预防。Objective To investigate the genotypes and phenotypes of infantile glycogen storage disease typeⅡ（GSDⅡ）with hypertrophic cardiomyopathy and the methods for birth defect prevention in the next child. Methods Four children with infantile GSDⅡ who were hospitalized,diagnosed,and treated in Department of Cardiology in Xi′an Children＇s Hospital from December 2016 to May 2017 were enrolled.Clinical and laboratory examinations were performed and analyzed,and the activity of acidic alpha-D-glucosidase（GAA）was measured.Sanger direct sequencing or next generation sequencing was performed to identify GAA gene mutations,and prenatal GAA gene mutation screening was performed for the next fetuses of the mothers of the two probands. Results Four children developed motor developmental delay,myasthenia,and myocardial hypertrophy at an age of2-8 months.The activity of GAA in three children was 2.5,2.1,and 1.9 nmol/（g·min）,respectively.Gene detection performed for four children identified 8 pathogenic mutations in the GAA gene,i.e.,p.R608 X,p.L701 P,p.R608 X,p.E888 X,p.W279 C,p.N535 Qfs＊3,p.S601 L,and p.E888 X.All four children died within 3-6 months after being diagnosed.Prenatal diagnosis was performed for the next child of the mothers of the two probands;one fetus carried a heterozygous mutation and was born successfully;the other carried the same compound heterozygous mutation as the proband and termination of pregnancy was performed. Conclusion Children with GSDⅡ carry pathogenic mutations from their parents.Symptoms of infantile GSDⅡappear early and children who do not receive enzyme replacement therapy have a high mortality rate.Although GSDⅡ has not been included in prenatal screening in China,GAA gene test for the next fetus of the proband＇s mother is helpful for the prevention of GSDⅡ birth defects.

关 键 词：糖原贮积病Ⅱ型 α葡糖苷酶类 突变 基因检测 优生学 

分 类 号：R725.891[医药卫生—儿科]