心肌病型极长链酰基辅酶A脱氢酶缺乏症一个家系的基因变异分析及产前诊断  

Analysis of ACADVL gene variant in a Chinese pedigree affected with Very-long-chain acl-CoA dehydrogenase deficiency

作　　者：宁昊丰 柴玉琼 王洁琼 王亚男 Ning Haofeng;Chai Yuqiong;Wang Jieqiong;Wang Ya′nan(Department of Medical Genetics and Antenatal Diagnosis,Luoyang Maternal and Child Health Care Hospital,Luoyang,Henan 471000,China)

机构地区：[1]洛阳市妇幼保健院医学遗传与产前诊断科,洛阳471000

出　　处：《中华医学遗传学杂志》2024年第10期1225-1230,共6页Chinese Journal of Medical Genetics

摘　　要：目的对1个拟诊为极长链酰基辅酶A脱氢酶缺乏症(VLCADD)的患儿进行基因检测,明确致病变异,为其家系的遗传咨询和产前诊断提供依据。方法利用全外显子组测序技术对患儿进行变异筛查,对ACADVL基因的疑似变异位点通过Sanger测序进行家系验证,根据美国医学遗传学与基因组学学会(ACMG)相关指南判断其致病性,并对再次妊娠的胎儿进行产前诊断。本研究通过洛阳市妇幼保健院医学伦理委员会的审查(伦理号:LYFY-YCCZ-2021003)。结果患儿ACADVL基因存在c.1532G>A/1827+2_1827+12del复合杂合变异,分别遗传自母亲和父亲,并判定为"可能致病性"和"致病性"。根据患儿的临床表现,结合血串联质谱分析及基因检测结果,诊断为心肌病型VLCADD。产前诊断结果显示胎儿具有同样的复合杂合变异,孕妇选择了终止妊娠。结论ACADVL基因的c.1532G>A/1827+2_1827+12del复合杂合变异可能是该家系患儿的遗传学病因。c.1827+2_1827+12del变异的发现丰富了ACADVL基因的突变谱。ObjectiveTo carry out genetic testing on a child diagnosed with Very-long-chain acyl-CoA dehydrogenase deficiency(VLADD)in order to provide a basis for genetic counseling and prenatal diagnosis for his family.MethodsWhole exome sequencing was performed for the proband.Candidate variant sites in the ACADVL gene were verified by Sanger sequencing,and their pathogenicity was predicted based on the guidelines from the American College of Medical Genetics and Genomics(ACMG).Prenatal diagnosis was performed on the fetus upon subsequent pregnancy.This study was approved by Medical Ethics Committe of the Luoyang Maternal and Child Health Care Hospital(Ethics No.LYFY-YCCZ-2021003).ResultsThe proband was found to harbor compound heterozygous variants of the ACADVL gene,namely c.1532G>A and 1827+2_1827+12del,which were inherited from his mother and father,and classified as likely pathogenic and pathogenic,respectively.By combining the clinical manifestations of the proband and the results of blood tandem mass spectrometry and genetic testing,the child was ultimately diagnosed as cardiomyopathy type VLADD.Prenatal diagnosis showed that the fetus has carried the same compound heterozygous variants,and the couple had opted to terminate the pregnancy.ConclusionThe c.1532G>A/1827+2_1827+12del compound heterozygous variants of the ACADVL gene probably underlay the pathogenesis of VLADD in this pedigree.The discovery of the 1827+2_1827+12del variant has enriched the mutational spectrum of the ACADVL gene.

关 键 词：极长链酰基辅酶A脱氢酶缺乏症 ACADVL基因 全外显子组测序 产前诊断 

分 类 号：R725.9[医药卫生—儿科]