标题：2-甲基丁酰-辅酶A脱氢酶缺乏症患者ACADSB基因变异分析

      作者：李莉 1，朱丹丹 2，张凤 1    1.泸州市妇幼保健院儿科，四川 泸州 646000；2.绵阳市第三人民医院(四川省精神卫生中心)，四川 绵阳 621000

      卷次： 2022年33卷1期

      【摘要】 目的 分析 2-甲基丁酰-辅酶A脱氢酶缺乏症(2-MBAD)患者的基因变异特点，明确其致病原因。方法 采集 2018—2020年就诊于泸州市妇幼保健院的 3例串联质谱发现异戊酰基肉碱(C5)升高疑似2-MBAD患者及其父母外周血并提取基因组DNA，应用高通量测序技术对患者进行遗传代谢性疾病基因检测，对疑似致病变异位点，父母进行 Sanger测序验证。结果 高通量测序结果显示：病例 1，ACADSB基因外显子 5,c.655G>A(p.V219M)(纯合变异)；病例 2，ACADSB基因外显子 10,c.1165 A>G(p.M389V)(纯合变异)；病例 3，ACADSB基因外显子5,c.655G>A(p.V219M)(杂合变异)，外显子10,c.1165 A>G(p.M389V)(杂合变异)，生物信息学分析预测为致病性。Sanger测序验证结果显示，3例患者父母的外周血DNA中均发现相应的杂合变异。结论 ACADSB基因变异可能为2-MBAD患者的致病原因，新变异的检出丰富了基因变异谱，为家系的遗传咨询提供了依据。
      【关键词】 2-甲基丁酰-辅酶A脱氢酶缺乏症；ACADSB基因；基因变异；异戊酰基肉碱
      【中图分类号】 R394 【文献标识码】 A 【文章编号】 1003—6350（2022）01—0093—03

Mutations of ACADSB gene associated with 2-methylbutyryl-CoA dehydrogenase deficiency.
LI Li 1, ZHUDan-dan 2, ZHANG Feng 1. 1. Department of Pediatric, Luzhou Provincial Hospital for Women and Children, Luzhou646000, Sichuan, CHINA; 2. Department of Pediatric, the Third Hospital of Mianyang, Mianyang 621000, Sichuan, CHINA
【Abstract】 Objective To detect the characteristics of gene mutations in patients with 2-methylbutyryl-CoA dehy-drogenase deficiency (2-MBAD), and identify the pathogenesis. Methods The peripheral blood samples were collectedfrom three patients of suspected 2-MBAD with elevated C5 by neonatal screening and their parents who visited in LuzhouMaternal and Child Health Hospital from 2018 to 2020. High throughput sequencing technology was used to detect the genesof genetic and metabolic diseases, and Sanger sequencing was used to verify the suspected mutation sites. Results Highthroughput sequencing showed in case 1, ACADSB gene exon 5,c.655g>A (p.V219M) (homozygous variation); in case 2,ACADSB gene exon 10,c.1165 A>G(p.M389V) (homozygous variation); in case 3, ACADSB gene exon 5,c.655G>A(p.V219M) (heterozygous variation), exon 10,c.1165 A>G(p.M389V) (heterozygous variation), which were predicted bybioinformatics analysis as pathogenicity. Sanger sequencing showed that heterozygous variants were found in the peripher-al blood DNA of the parents of the three patients. Conclusion ACADSB gene mutation may be a potential pathogenesisof 2-MBAD, which would expand the gene mutation spectrum and provide basis for family genetic counseling.
      【Key words】 2-methylbutyryl-CoA dehydrogenase deficiency; ACADSB gene; Gene mutations; Isovaleryl car-nitine 2-methylbutyrylcarnitine·短篇论著·doi:10.3969/j.issn.1003-6350.2022.01.026