Orii K O, Aoyama T, Souri M, Orii K E, Kondo N, Orii T, Hashimoto T
Department of Pediatrics, Gifu University School of Medicine, Japan.
Biochem Biophys Res Commun. 1995 Dec 26;217(3):987-92. doi: 10.1006/bbrc.1995.2867.
Very-long-chain acyl-CoA dehydrogenase (VLCAD) is a major enzyme catalyzing long-chain fatty acids in the first step of mitochondrial beta-oxidation system. Inborn error of this enzyme can cause sudden infant death syndrome and hypertrophic cardiomyopathy is present at a significantly high frequency. To investigate VLCAD deficiency at the genomic DNA level, we cloned the VLCAD gene and analyzed the structure. The gene is about 5.4 kb long and contains 20 exons. We performed mutation analysis in two patients, both having a 105 bp deletion encompassing bases 1078-1182 in cDNA. A point mutation (GT-->AT) at 5' splice site of intron 11 was identified in both patients. This mutation seems to cause skipping of exon 11 corresponding to the 105 bp deletion. This is the first documentation of aberrant splicing in the VLCAD gene.
极长链酰基辅酶A脱氢酶（VLCAD）是线粒体β-氧化系统第一步中催化长链脂肪酸的主要酶。该酶的先天性缺陷可导致婴儿猝死综合征，肥厚型心肌病的发生率也显著较高。为了在基因组DNA水平上研究VLCAD缺乏症，我们克隆了VLCAD基因并分析了其结构。该基因长约5.4kb，包含20个外显子。我们对两名患者进行了突变分析，这两名患者的cDNA中均有一个105bp的缺失，涵盖碱基1078 - 1182。在两名患者中均鉴定出内含子11的5'剪接位点处的一个点突变（GT→AT）。该突变似乎导致对应于105bp缺失的外显子11跳跃。这是VLCAD基因异常剪接的首次记录。
