一个脑肌酸缺乏综合征2型家系的基因分析和治疗  

Genetic analysis and treatment for an infant with cerebral creatine deficiency syndrome type 2

作　　者：孙卫华[1] 吴冰冰[1] 吴梦圆 杨宾[1] 张萍[1] 肖非凡 施亿贇[1] 吴鸿疆 周文浩[1] Sun Weihua;Wu Bingbing;Wu Mengyuan;Yang Bin;Zhang Ping;Xiao Feifan;Shi Yiyun;Wu Hongjiang;Zhou Wenhao(Children’s Hospital of Fudan University,Shanghai Key Laboratory of Birth Defects,Translational Medicine Center of Children’s Development and Disease of Fudan University,Shanghai 201102,China)

机构地区：[1]复旦大学附属儿科医院,上海市出生缺陷防治重点实验室,复旦大学儿童发育与疾病转化医学研究中心,上海201102

出　　处：《中华医学遗传学杂志》2020年第9期1001-1004,共4页Chinese Journal of Medical Genetics

基　　金：上海市科学技术委员会项目(15XD1500800)。

摘　　要：目的对1例脑肌酸缺乏综合征(cerebral creatine deficiency syndrome,CCDS)2型患儿及家系进行基因测序和代谢物检测,明确其遗传学病因和类型。方法应用二代测序及PCR-Sanger验证,代谢物采用串联质谱和磁共振波谱分析。结果检测到患儿GAMT基因2个新变异c.289delC和c.392-1G>C,分别来自父亲和母亲。患儿血/脑肌酸浓度均明显下降。确诊后进行临床干预,血肌酸和胍基乙酸浓度很快恢复正常,2个月后脑肌酸浓度也得到明显改善,临床症状取得显著进步。结论通过家系分析,明确c.289delC和c.392-1G>C变异为致病原因,并为产前诊断提供了依据,丰富了GAMT基因变异谱。目前治疗对患儿具明显疗效。Objective To carry out genetic and metabolite analysis for an infant with cerebral creatine deficiency syndrome type 2(CCDS2).Methods Clinical data of the child was collected.Whole-exome sequencing was carried out to identify potential variants by next generation sequencing.Candidate variants were confirmed by Sanger sequencing.Metabolites were determined by tandem mass spectrometry and magnetic resonance spectroscopy.Treatment was carried out following the diagnosis and genetic counseling for the affected family.Results Two novel heterozygous variants(c.289delC and c.392-1G>C)of the GAMT gene were identified in the proband,which were respectively inherited from her father and mother.In silico analysis suggested both variants to be pathogenic.Creatine(Cr)level of the child was very low,and cerebral guanidinoacetate(GAA)level was slightly increased.But both had recovered to normal in two weeks,and cerebral Cr level was significantly improved after two months.Intellectual and motor development of the child were significantly improved.Conclusion The child was diagnosed with CCDS type 2,for which pathogenic variants of the GAMT gene may be accountable.Treatment has attained a satisfactory effect for the patient.

关 键 词：脑肌酸缺乏综合征 肌酸 GAMT基因 基因测序 治疗 

分 类 号：R725.9[医药卫生—儿科] R440[医药卫生—临床医学]