The frequency of short-chain acyl-CoA dehydrogenase gene variants in the US population and correlation with the C4-acylcarnitine concentration in newborn blood spots
The frequency of short-chain acyl-CoA dehydrogenase gene variants in the US population and correlation with the C4-acylcarnitine concentration in newborn blood spots
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DOI：
10.1016/s1096-7192(03)00034-9
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发表时间：
2003-04-01
影响因子：
3.8
通讯作者：
Matern, D
中科院分区：
文献类型：
--
作者：
Nagan, N;Kruckeberg, KE;Matern, D
短链酰辅酶A脱氢酶(SCAD)缺乏症是一种临床异质性疾病。临床表型不一，从早期的致命性代谢失代偿到轻微的成人发病，一些患者仍然没有症状。在SCAD基因外显子5和6中发现了两个突变(511C和GT；T；625G和GT；A)。尽管它们改变了SCAD蛋白的结构和催化性质，但这些变异并不是真正的致病突变，而是赋予疾病易感性。此前的研究发现，这些基因变异在欧洲人中很常见。我们的目标是确定这些变异在美国人群中的频率，并确定这些变异的存在是否与新生儿血斑中丁基卡尼汀(C-4-酰卡尼汀)浓度升高有关。通过对694个样本的分析，发现625G；A变异的等位基因频率(22%)显著高于511C&gT；T变异的等位基因频率(3%)。这些基因变异在7%的研究人群中以纯合子或复合杂合子的形式被检测到。此外，西班牙裔人群中625G>；A等位基因的频率(30%)显著高于非裔美国人(9%)和亚裔人群(13%)。在三名非裔美国新生儿(0.3%)中发现了一种以前未报道的变异，IVS 5(-10)C>；T。与野生型纯合子相比，625A变异纯合子受试者血斑中C-4-酰基肉碱浓度显著升高(p<；0.0001)。然而，没有一种观察到的基因型与C4-酰基肉碱的浓度相关，这与SCAD缺乏症的生化诊断一致。(C)2003年埃尔塞维尔科学公司(美国)。版权所有。
Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is a clinically heterogeneous disorder. The clinical phenotype varies from fatal metabolic decompensation in early life to subtle adult onset, some patients remain asymptomatic. Two mutations (511C > T; 625G > A) have been described in exons 5 and 6 of the SCAD gene. Although they alter the structural and catalytic properties of the SCAD protein, these variants are not true disease-causing mutations but confer disease susceptibility. Previous studies found these gene variants to be common in Europeans. We aimed to establish the frequency of these variants in the US population and to determine whether the presence of these variants correlates with elevated butyrylcarnitine (C-4-acylcarnitine) concentrations in newborn blood spots. Based on the analysis of 694 samples, we found that the allele frequency of the 625G > A variant was significantly higher (22%) than that of the 511C > T variant (3%). These gene variants were detected in either homozygous or compound heterozygous form in 7% of the study population. Additionally, the frequency of the 625G > A allele in the Hispanic population (30%) was significantly higher than that of the African-American (9%) and Asian (13%) subpopulations. A previously unreported variant, IVS 5 (-10) C > T, was identified in three African-American newborns (0.3%). The C-4-acylcarnitine concentration in blood spots was significantly higher in subjects homozygous for the 625A variant when compared to those homozygous for the wild type (p < 0.0001). However, none of the observed genotypes was associated with a concentration of C4-acylcarnitine that would be consistent with a biochemical diagnosis of SCAD deficiency. (C) 2003 Elsevier Science (USA). All rights reserved.