Characterization of N93S, I312T, and A333P missense mutations in two Japanese families with mitochondrial acetoacetyl-CoA thiolase deficiency

Fukao, Toshiyuki; Nakamura, Haruki; Song, Xiaolin; Nakamura, Kozue; Orii, Kenji E.; Kohno, Yusuke; Kano, Masatsugu; Yamaguchi, Seiji; Hashimoto, Takashi; Orii, Tadao; Kondo, Naomi

doi:10.1002/(sici)1098-1004(1998)12:4<245::aid-humu5>3.0.co;2-e

Cited by 35 publications

(36 citation statements)

References 34 publications

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“…Insoluble mutant T2 proteins p.Ala215Asn, p.Met193Arg, and c.1012_1015dup were detected only in pellets. These three mutations appear to have drastic effects on T2 protein structure, like p.Ala333Pro, which was also identified only in pellets (Fukao et al 1998). Although having no residual enzymatic activities, some mutant T2 proteins are soluble.…”

Section: Discussionmentioning

confidence: 99%

“…The average of three independent experiments Values for pH, HCO 3 , BE, and glucose are shown in mmol/L, whereas NH was calculated. In addition, both supernatants and pellets of cell extracts were subjected to immunoblot analysis as described (Fukao et al 1997(Fukao et al , 1998. The first antibody was a mixture of an anti-T2 antibody and anti-succinyl-CoA:3-oxoacid CoA transferase (SCOT) antibody, as previously described (Fukao et al 1997).…”

Section: Transient Expression Analysesmentioning

confidence: 92%

“…The 12 ACAT1 exons, with their intron boundaries, were amplified by PCR using formerly designed primer pairs and conditions (Fukao et al 1998). The 12 amplified fragments were sequenced using a BigDye ® Terminator v1.1 cycle sequencing kit (Applied Biosystems, Foster City, CA, USA) and an ABI PRISM 3130XL genetic analyzer (Applied Biosystems) according to the manufacturer's directions.…”

Section: Mutation Analysismentioning

confidence: 99%

“…Transient expression analyses of T2 cDNA were performed using a pCAGGS eukaryote expression vector, as previously described (Niwa et al 1991;Fukao et al 1998;Zhang et al 2004). Briefly, we used a Kod-Plus-Mutagenesis Kit ® (Tyobo Co., Osaka, Japan) to construct four full-length mutant cDNA: p.Met193Arg, p.Ile323Thr, p.Ala215Asn, and c.1012_1015dup.…”

Section: Transient Expression Analysesmentioning

confidence: 99%

“…We measured the difference of thiolase activity in the absence and the presence of potassium ions, which specifically stimulate T2; such a difference represents T2 activity (Fukao et al 1998;Zhang et al 2004). The average of three independent experiments Values for pH, HCO 3 , BE, and glucose are shown in mmol/L, whereas NH was calculated.…”

Section: Transient Expression Analysesmentioning

confidence: 99%

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Clinical and Mutational Characterizations of Ten Indian Patients with Beta-Ketothiolase Deficiency

Abdelkreem

Akella

Dave³

et al. 2016

JIMD Reports

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Beta-ketothiolase deficiency (mitochondrial acetoacetyl-CoA thiolase (T2) deficiency) is an inherited disease of isoleucine catabolism and ketone body utilization caused by ACAT1 mutations. We identified ten Indian patients who manifested with ketoacidotic episodes of variable severity. The patients showed increased urinary excretion of isoleucine-catabolic intermediates: 2-methyl-3-hydroxybutyrate, 2-methylacetoacetate, and tiglylglycine.

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Section: Discussionmentioning

confidence: 99%

Section: Transient Expression Analysesmentioning

confidence: 92%

Section: Mutation Analysismentioning

confidence: 99%

Section: Transient Expression Analysesmentioning

confidence: 99%

Section: Transient Expression Analysesmentioning

confidence: 99%

See 3 more Smart Citations

Clinical and Mutational Characterizations of Ten Indian Patients with Beta-Ketothiolase Deficiency

Abdelkreem

Akella

Dave³

et al. 2016

JIMD Reports

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Acetoacetyl‐ Co A Thiolase (Mitochondrial)

Fukao

2002

Wiley Encyclopedia of Molecular Medicine

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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

et al. 2003

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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.

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Characterization of N93S, I312T, and A333P missense mutations in two Japanese families with mitochondrial acetoacetyl-CoA thiolase deficiency

Cited by 35 publications

References 34 publications

Clinical and Mutational Characterizations of Ten Indian Patients with Beta-Ketothiolase Deficiency

Clinical and Mutational Characterizations of Ten Indian Patients with Beta-Ketothiolase Deficiency

Acetoacetyl‐ Co A Thiolase (Mitochondrial)

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

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