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.