背景:4例超长链酰基辅酶A脱氢酶缺乏症(VLCADD)患者的生化和遗传特征,明确其致病遗传因素,评价遗传诊断在VLCADD早期诊断中的应用价值,在本文中进行了报道和讨论。方法:患者接受血液串联质谱(MS/MS),尿气相色谱(GC/MS),和高通量测序技术。使用生物信息学软件分析新变体的致病性。Swiss-PdbViewer软件用于预测变体对超长链酰基辅酶A脱氢酶(VLCAD)蛋白结构的影响。结果:共确诊4例VLCADD患者。他们揭示了C14,C14:1,C14:2,C14:1/C2,C14:1/C10和C14:1/C12:1的水平升高。2例患者均为早发性新生儿病例,在婴儿期和新生儿期死亡,分别。检测到7种变异,包括四个新颖的变体。生物信息学软件显示这些变异是有害的,Swiss-PdbViewer结果表明变异会影响蛋白质构象。结论:本研究鉴定了四种新的ACADVL基因变体。这些发现有助于了解VLCADD的遗传基础和发病机理。同时,该研究丰富了VLCADD的基因突变谱和基因型与表型的相关性,提示基因诊断在VLCADD的早期诊断和治疗中起着至关重要的作用。
Background: The biochemical and genetic characteristics of four very-long-chain acyl-coenzyme A dehydrogenase deficiency (
VLCADD) patients, clarifying their pathogenic genetic factors and evaluating the application value of genetic diagnosis in the early diagnosis of
VLCADD, are reported and discussed in this article. Methods: Patients underwent blood tandem mass spectrometry (MS/MS), urine gas chromatography (GC/MS), and high-throughput sequencing technology. New variants were analyzed for pathogenicity using bioinformatics software. Swiss-PdbViewer software was used to predict the effect of variants on the structure of the very-long-chain acyl-CoA dehydrogenase (VLCAD) protein. Result: A total of four
VLCADD patients were diagnosed. They revealed elevated levels of C14, C14:1, C14:2, C14:1/C2, C14:1/C10, and C14:1/C12:1. Two patients were early-onset neonatal cases and died during infancy and the neonatal period, respectively. Seven kinds of variants were detected, including four novel variants. Bioinformatics software revealed that the variants were harmful, and the Swiss-PdbViewer results suggest that variation affects protein conformation. Conclusion: This study identified four novel ACADVL gene variants. These findings contribute to the understanding of the genetic basis and pathogenesis of
VLCADD. Meanwhile, the study enriches the genetic mutation spectrum and the correlation between genotypes and phenotypes of VLCADD, indicating that genetic diagnosis plays an essential role in the early diagnosis and treatment of
VLCADD.