کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1998966 | 1065832 | 2007 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Single-base substitution at the last nucleotide of exon 6 (c.671G>A), resulting in the skipping of exon 6, and exons 6 and 7 in human Succinyl-CoA:3-ketoacid CoA transferase (SCOT) gene Single-base substitution at the last nucleotide of exon 6 (c.671G>A), resulting in the skipping of exon 6, and exons 6 and 7 in human Succinyl-CoA:3-ketoacid CoA transferase (SCOT) gene](/preview/png/1998966.png)
Succinyl-CoA:3-ketoacid CoA transferase (SCOT, EC 2.8.3.5) is the key enzyme for ketone body utilization. Hereditary SCOT deficiency (MIM 245050) causes episodes of severe ketoacidosis. We identified a homozygous point mutation (c.671G>A) , which is a single-base substitution at the last nucleotide of exon 6, in a Turkish patient (GS12) with SCOT deficiency. This point mutation resulted in the skipping of exon 6, and exons 6 and 7 in human SCOT genes. To understand why the c.671G>A causes exons 6 and 7 skipping, nuclear RNA was separated from cytoplasmic RNA and both were analyzed by RT-PCR. In nuclear RNA, SCOT mRNA with exon 6 skipping was predominant and mRNA with exons 6 and 7 skipping was hardly detected, whereas the latter became one of major mRNA species in cytoplasmic RNA. This discrepancy was interpreted as follows: exon 6 skipping causes a frameshift and nonsense-mediated RNA decay in the cytosol, so mRNA with exon 6 skipping was unstable. On the other hand, SCOT mRNA with exons 6 and 7 is a minor transcript but it retains the reading-frame and is stable in cytosol. As a result, the latter mRNA is more abundant under steady-state conditions as compared to the former mRNA.
Journal: Molecular Genetics and Metabolism - Volume 90, Issue 3, March 2007, Pages 291–297