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Single base substitutions at the initiator codon in the mitochondrial acetoacetyl-CoA thiolase (ACAT1/T2) gene result in production of varying amounts of wild-type T2 polypeptide.
- Source :
-
Human mutation [Hum Mutat] 2003 Jun; Vol. 21 (6), pp. 587-92. - Publication Year :
- 2003
-
Abstract
- Initiator codon mutations are relatively uncommon and less well characterized compared to other types of mutations. We identified a novel initiator codon mutation (c.2T>C) heterozygously in a Japanese patient (Patient GK30) with mitochondrial acetoacetyl-CoA thiolase (T2) gene deficiency (ACAT1 deficiency); c.149delC was on the other allele. We examined translation efficiencies of nine mutant T2 cDNAs harboring one-base substitutions at the initiator methionine codon using in vivo transient expression analysis. We found that all the mutants produced wild-type T2 polypeptide, to various degrees (wild type (100%) > c.1A>C (66%) > c.2T>C, c.3G>C, c.3G>T (22%) > c3G>A, c.1A>G (11%) > c.2T>A, c.2T>G, c.1A>T (7.4%)). T2 mRNA expression levels in Patient GK08 (a homozygote of c.2T>A) and Patient GK30 fibroblasts, respectively, were almost the same as in control fibroblasts, when examined using semiquantitative PCR. This means that initiator codon mutations did not affect T2 mRNA levels. We propose that all one-base substitutions at the initiator methionine codon in the T2 gene could be mutations, which retain some residual T2 activity.<br /> (Copyright 2003 Wiley-Liss, Inc.)
- Subjects :
- Acetyl-CoA C-Acetyltransferase biosynthesis
Acetyl-CoA C-Acetyltransferase deficiency
Cell Line
DNA Mutational Analysis
DNA, Complementary genetics
Female
Heterozygote
Humans
Infant
Japan
Male
Molecular Sequence Data
Protein Biosynthesis
RNA, Messenger genetics
RNA, Messenger metabolism
Acetyl-CoA C-Acetyltransferase genetics
Codon, Initiator genetics
Mitochondria enzymology
Mitochondria genetics
Peptides genetics
Point Mutation genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1098-1004
- Volume :
- 21
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Human mutation
- Publication Type :
- Academic Journal
- Accession number :
- 12754704
- Full Text :
- https://doi.org/10.1002/humu.10209