Single-base substitution at the last nucleotide of exon 6 (c.671G&gt;A), resulting in the skipping of exon 6, and exons 6 and 7 in human Succinyl-CoA:3-ketoacid CoA transferase (SCOT) gene

Yamada, Keitaro; Fukao, Toshiyuki; Zhang, Gaixiu; Sakurai, Satomi; Ruiter, J. P. N.; Wanders, Ronald J. A.; Kondo, Naomi

doi:10.1016/j.ymgme.2006.10.010

Cited by 20 publications

(12 citation statements)

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“…There are several reports of mutations at single-splice junctions that result in the skipping of two or more exons [Fang et al, 2001;Haire et al, 1997;Hayashida et al, 1994;Schneider et al, 1993;Takahara et al, 2002;Yamada et al, 2007]. The splicing order of introns can explain the events of aberrant splicing.…”

Section: Discussionmentioning

confidence: 99%

“…SCOT deficiency (MIM #245050), clinically characterized by episodes of severe ketoacidosis, is an autosomal recessive inborn error of metabolism, first described in 1972 [Tildon and Cornblath, 1972]. Since the first description of SCOT deficiency, fewer than 30 affected probands have been reported including personal communications [Baric et al, 2001;Berry et al, 2001;Cornblath et al, 1971;Fukao et al, 1996Fukao et al, , 2000Fukao et al, , 2004Fukao et al, , 2006Fukao et al, , 2007Fukao et al, , 2010Fukao et al, , 2011Kassovska-Bratinova et al, 1996;Longo et al, 2004;Merron and Akhtar, 2009;Niezen-Koning et al, 1997;Perez-Cerda et al, 1992;Pretorius et al, 1996;Rolland et al, 1998;Sakazaki et al, 1995;Snyderman et al, 1998;Song et al, 1998;Tildon and Cornblath, 1972;Yamada et al, 2007].…”

Section: Introductionmentioning

confidence: 99%

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Molecular Basis of Two-Exon Skipping (Exons 12 and 13) by c.1248+5g>a inOXCT1Gene: Study on Intermediates ofOXCT1Transcripts in Fibroblasts

et al. 2013

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The molecular basis of simultaneous two-exon skipping induced by a splice-site mutation has yet to be completely explained. The splice donor site mutation c.1248+5g>a (IVS13) of the OXCT1 gene resulted predominantly in skipping of exons 12 and 13 in fibroblasts from a patient (GS23) with succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency. We compared heteronuclear RNA (hnRNA) intermediates between controls' and GS23's fibroblasts. Our strategy was to use RT-PCR of hnRNA to detect the presence or absence of spliced exon clusters in RNA intermediates (SECRIs) comprising sequential exons. Our initial hypothesis was that a SECRI comprising exons 12 and 13 was formed first followed by skipping of this SECRI in GS23 cells. However, such a pathway was revealed to be not a major one. Hence, we compared the intron removal of SCOT transcript between controls and GS23. In controls, intron 11 was the last intron to be spliced and the removal of intron 12 was also rather slow and occurred after the removal of intron 13 in a major pathway. However, the mutation in GS23 cells resulted in retention of intron 13, thus causing the retention of introns 12 and 11. This "splicing paralysis" may be solved by skipping the whole intron 11-exon 12-intron 12-exon 13-mutated intron 13, resulting in skipping of exons 12 and 13.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular Basis of Two-Exon Skipping (Exons 12 and 13) by c.1248+5g>a inOXCT1Gene: Study on Intermediates ofOXCT1Transcripts in Fibroblasts

et al. 2013

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“…and follows an autosomal recessive mode of inheritance. More than 30 patients have been reported or are known to the authors (Cornblath et al 1971;T i l d o na n d Cornblath 1972; Perez-Cerda et al 1992; Sakazaki et al 1995; Kassovska-Bratinova et al 1996; Pretorius et al 1996; Niezen-Koning et al 1997; Rolland et al 1998;S n y d e r m a n et al 1998;Song et al 1998;Fukao et al 2000Fukao et al , 2004bFukao et al , 2006Fukao et al , 2007aFukao et al , 2010bFukao et al , 2011Baric et al 2001;Berry et al 2001;Longo et al 2004;Yamada et al 2007;Merron and Akhtar 2009; …”

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confidence: 99%

Ketone body metabolism and its defects

Fukao

Mitchell

Sass

et al. 2014

J of Inher Metab Disea

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194

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Acetoacetate (AcAc) and 3-hydroxybutyrate (3HB), the two main ketone bodies of humans, are important vectors of energy transport from the liver to extrahepatic tissues, especially during fasting, when glucose supply is low. Blood total ketone body (TKB) levels should be evaluated in the context of clinical history, such as fasting time and ketogenic stresses. Blood TKB should also be evaluated in parallel with blood glucose and free fatty acids (FFA). The FFA/TKB ratio is especially useful for evaluation of ketone body metabolism. Defects in ketogenesis include mitochondrial HMG-CoA synthase (mHS) deficiency and HMG-CoA lyase (HL) deficiency. mHS deficiency should be considered in non-ketotic hypoglycemia if a fatty acid beta-oxidation defect is suspected, but cannot be confirmed. Patients with HL deficiency can develop hypoglycemic crises and neurological symptoms even in adolescents and adults. Succinyl-CoA-3-oxoacid CoA transferase (SCOT) deficiency and beta-ketothiolase (T2) deficiency are two defects in ketolysis. Permanent ketosis is pathognomonic for SCOT deficiency. However, patients with "mild" SCOT mutations may have nonketotic periods. T2-deficient patients with "mild" mutations may have normal blood acylcarnitine profiles even in ketoacidotic crises. T2 deficient patients cannot be detected in a reliable manner by newborn screening using acylcarnitines. We review recent data on clinical presentation, metabolite profiles and the course of these diseases in adults, including in pregnancy.

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“…Substitutions of the last nucleotide of an exon have been reported to disrupt the normal splicing and lead to the deletion of the entire exon [6], skipping of more than one exon [7] or deletion of part of the exon through the creation of a cryptic splicing site [8]. In other cases, exon skipping can cause a frameshift resulting in aberrant mRNA that is degraded by nonsense-mediated RNA decay, making the abnormal transcript hard to detect [9].…”

Section: Introductionmentioning

confidence: 99%

The germline CDH1 c.48 G > C substitution contributes to cancer predisposition through generation of a pro-invasive mutation

Zhang¹,

Xiao²,

Ruggeri³

et al. 2014

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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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

Cited by 20 publications

References 36 publications

Molecular Basis of Two-Exon Skipping (Exons 12 and 13) by c.1248+5g>a inOXCT1Gene: Study on Intermediates ofOXCT1Transcripts in Fibroblasts

Molecular Basis of Two-Exon Skipping (Exons 12 and 13) by c.1248+5g>a inOXCT1Gene: Study on Intermediates ofOXCT1Transcripts in Fibroblasts

Ketone body metabolism and its defects

The germline CDH1 c.48 G > C substitution contributes to cancer predisposition through generation of a pro-invasive mutation

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