全外显子测序对4例极长链酰基辅酶A脱氢酶缺乏症患儿遗传病因研究

Study on genetic etiology of four cases with very long-chain acyl-CoA dehydrogenase deficiency(VLCADD) using whole-exome sequencing

目的 对4例极长链酰基辅酶A脱氢酶缺乏症(VLCADD)患儿进行全外显子测序以明确其遗传学病因。方法 收集4例VLCADD患儿及其家属外周血,提取DNA,采用全外显子组测序进行致病基因检测,并通过Sanger测序和家系验证确认其遗传方式,利用生物信息学软件对变异位点进行功能分析。结果 结合全外显子组测序及Sanger测序结果,4例VLCADD患儿在ACADVL基因共检出6个变异,致病变异分别来自父母双方,符合常染色体隐性遗传。其中4个变异即c.226_227insGAAT、c.621_622del、c.151A>T、c.1194C>G尚未见于国内外报道,与其新生儿串联质谱筛查结果和(或)临床症状吻合。结论 本研究结果丰富了VLCADD基因突变谱,为临床VLCADD筛查和诊断提供了重要依据。

Objective To determine the genetic etiology for four child patients with very long-chain acyl-CoA dehydrogenase deficiency(VLCADD) via whole-exome sequencing(WES).Method The genomic DNA was extracted from the peripheral blood of 4 unrelated VLCADD families.The WES identified pathogenic variants were verified via Sanger sequencing,and their parental origins were confirmed.In Silico analysis were conducted using ioinformatics software.Result Combined with whole-exome sequencing and Sanger sequencing,six ACADVL variants were identified in 4 VLCADD probands.In each proband,the variants were inherited from both parents,which was consistent with autosomal recessive inheritance.Four of the variants,c.226_227insGAAT,c.621_622del,c.151A>T,c.1194C>G,were first reported,and were consistent with the probands' neonatal tandem mass spectrometry screening results and(or) clinical symptoms.Conclusion Our finding enriched the VLCADD gene mutation spectrum,and provided basis for clinical screening and diagnosis of VLCADD.