摘要
目的对1例极长链酰基辅酶A脱氢酶缺乏症(VLCADD)病儿进行可疑致病基因突变分析,并探讨基因突变与该疾病表型的关系。方法选择1例VLCADD病儿为实验组,200例健康者为对照组,采用串联质谱法检测VLCADD的酰基肉碱谱,全部外显子测序技术(WES)进行突变筛查,与gnomAD和1000Genomes数据库中的人类基因组序列进行比对,寻找可疑基因突变位点,并在病儿及其父母中进行Sanger测序验证。结果病儿串联质谱结果显示,VLCADD相关特征性指标十四烯酰基肉碱(C14∶1)升高,尤其是升高值>1.0μmol/L可明确诊断。WES发现病儿ACADVL基因存在复合杂合突变,第8外显子c.664G>A和第13外显子c.1276G>A。Sanger测序验证c.664G>A来源于母亲,c.1276G>A来源于父亲。200例正常对照者中未发现该突变。结论ACADVL基因c.664G>A和c.1276G>A复合杂合突变可能是VLCADD的致病突变,串联质谱检测结合高通量基因测序可为VLCADD的临床早期筛查和诊断提供重要依据。
Objective To analyze the suspected pathogenic gene mutations in a child with very long-chain acyl-CoA dehydrogenase deficiency(VLCADD),and to investigate the relationship between gene mutation and the phenotype of the disease.Me-thodsA child with VLCADD was assigned to the experimental group and 200 healthy subjects were assigned to the control group.The acyl carnitine profile in the child with VLCADD was determined by tandem mass spectrometry,the mutation screening was performed by whole exon sequencing,and the suspected gene mutation sites were identified by alignment against the human genome sequences in gnomAD and 1000Genomes database.Verification with Sanger sequencing was performed for the child and the parents.Results Tandem mass spectrometry showed increased tetradecenoylcarnitine(C14∶1)as an indicator of VLCADD,and the diagnosis was confirmed by an increase of>1μmol/L.Whole exon sequencing revealed complex heterozygous mutations in[STBX]ACADVL[STBZ]gene in Exon 8(c.664G>A)and Exon 13(c.1276G>A).Sanger sequencing confirmed that c.664G>A came from the mother and c.1276G>A came from the father.These mutations were not found in 200 normal subjects.ConclusionThe complex heterozygous mutations c.664G>A and c.1276G>A in ACADVL may be the pathogenic mutations of VLCADD.Tandem mass spectrometry combined with high-throughput gene sequencing provides an important basis for early clinical screening and diagnosis of VLCADD.
作者
李玲
巩霞
张铷
郑璇
张仁伟
刘世国
LI Ling;GONG Xia;ZHANG Ru;ZHENG Xuan;ZHANG Renwei;LIU Shiguo(Department of Medical Genetics,The Affiliated Hospital of Qingdao University,Qingdao 266003,China)
出处
《青岛大学学报（医学版）》
CAS
2024年第2期180-183,共4页
Journal of Qingdao University(Medical Sciences)
基金
国家自然科学基金项目(82071683)。
关键词
极长链酰基辅酶A脱氢酶缺乏症
串联质谱法
DNA突变分析
very long-chain acyl coenzyme A dehydrogenase deficiency
tandem mass spectrometry
DNA mutational analysis
