OXCT1, IVS13DS, G-A, +5 AND Succinyl-CoA acetoacetate transferase deficiency

Clinical significance:Pathogenic (Last evaluated: Jul 30, 2013)

Review status:1 star out of maximum of 4 stars

classified by single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000034378.3

Allele description [Variation Report for OXCT1, IVS13DS, G-A, +5]

Gene:
OXCT1:3-oxoacid CoA transferase 1 [Gene - OMIM]
Variant type:
single nucleotide variant
Cytogenetic location:
5p13
HGVS:
    Nucleotide change:
    IVS13DS, G-A, +5
    Links:
    OMIM: 601424.0007

    Condition(s)

    Name:
    Succinyl-CoA acetoacetate transferase deficiency
    Synonyms:
    SUCCINYL-CoA:3-KETOACID CoA-TRANSFERASE DEFICIENCY; Succinyl-CoA:3-oxoacid CoA transferase deficiency
    Identifiers:
    MedGen: C0342792; Orphanet: 832; OMIM: 245050
    Age of onset:
    Neonatal/infancy
    Prevalence:
    <1 / 1 000 000 832

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    Assertion and evidence details

    Submission AccessionSubmitterReview StatusClinical Significance
    (Last evaluated)
    OriginMethodConsequenceCitations
    SCV000058362OMIMPathogenic
    (Jul 30, 2013)
    germlineliterature only

    PubMed (1)
    [See all records that cite this PMID]

    Summary from all submissions

    EthnicityOriginAffectedAlleles observedFamiliesChromosomes testedNumber TestedFamily historyMethod
    not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

    Citations

    PubMed

    Molecular basis of two-exon skipping (exons 12 and 13) by c.1248+5g>a in OXCT1 gene: study on intermediates of OXCT1 transcripts in fibroblasts.

    Hori T, Fukao T, Murase K, Sakaguchi N, Harding CO, Kondo N.

    Hum Mutat. 2013 Mar;34(3):473-80. doi: 10.1002/humu.22258. Epub 2013 Jan 22.

    PubMed [citation]
    PMID:
    23281106

    Details of each submission

    From OMIM, SCV000058362.2

    #EthnicityAlleles ObservedChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedliterature only PubMed (1)

    Description

    In a 7-month-old boy of Mexican origin with SCOT deficiency (245050), Hori et al. (2013) identified a homozygous G-to-A transition in intron 13 of the OXCT1 gene (1248+5G-A). RT-PCR analysis of patient cells showed 2 aberrant transcripts: a major transcript lacking exons 12 and 13 and subject to nonsense-mediated mRNA decay, and a minor in-frame transcript lacking exons 8 to 13. Patient fibroblasts showed less than 10% residual OXCT1 activity and lack of detectable protein on immunoblot analysis. Analysis of heteronuclear RNA to detect spliced exon clusters in RNA intermediates (SECRIs) showed that in controls intron 11 was the last intron to be spliced, and that intron 12 was removed after the removal of intron 13 in control cells. In contrast, patient cells showed the retention of intron 13, thus causing retention of introns 12 and 11. This splicing abnormality would result in the skipping of a block of the transcript including intron 11-exon 12-intron 12-exon 13-mutated intron 13, resulting in the skipping of both exons 12 and 13. The patient had recurrent ketoacidotic episodes in association with recurrent infections beginning at age 7 months. He then had permanent ketosis.

    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodVariant allelesAllele frequencyFamiliesCo-occurrences
    1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

    Last Updated: Oct 30, 2014

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