NM_000108.5(DLD):c.1178T>C (p.Ile393Thr) AND Maple syrup urine disease, type 3

Clinical significance:Pathogenic (Last evaluated: Mar 1, 2005)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000012747.18

Allele description [Variation Report for NM_000108.5(DLD):c.1178T>C (p.Ile393Thr)]

NM_000108.5(DLD):c.1178T>C (p.Ile393Thr)

Gene:
DLD:dihydrolipoamide dehydrogenase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q31.1
Genomic location:
Preferred name:
NM_000108.5(DLD):c.1178T>C (p.Ile393Thr)
HGVS:
  • NC_000007.14:g.107917404T>C
  • NG_008045.1:g.31264T>C
  • NM_000108.5:c.1178T>CMANE SELECT
  • NM_001289750.1:c.881T>C
  • NM_001289751.1:c.1109T>C
  • NM_001289752.1:c.1034T>C
  • NP_000099.2:p.Ile393Thr
  • NP_001276679.1:p.Ile294Thr
  • NP_001276680.1:p.Ile370Thr
  • NP_001276681.1:p.Ile345Thr
  • NC_000007.13:g.107557849T>C
  • P09622:p.Ile393Thr
Protein change:
I294T; ILE393THR
Links:
UniProtKB: P09622#VAR_076989; OMIM: 238331.0007; dbSNP: rs121964991
NCBI 1000 Genomes Browser:
rs121964991
Molecular consequence:
  • NM_000108.5:c.1178T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001289750.1:c.881T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001289751.1:c.1109T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001289752.1:c.1034T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Maple syrup urine disease, type 3 (MSUD3)
Synonyms:
MAPLE SYRUP URINE DISEASE, TYPE III; DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY; E3 DEFICIENCY; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009529; MedGen: CN043137; Orphanet: 2394; Orphanet: 765; OMIM: 246900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000032982OMIMno assertion criteria providedPathogenic
(Mar 1, 2005)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Leigh syndrome due to compound heterozygosity of dihydrolipoamide dehydrogenase gene mutations. Description of the first E3 splice site mutation.

Grafakou O, Oexle K, van den Heuvel L, Smeets R, Trijbels F, Goebel HH, Bosshard N, Superti-Furga A, Steinmann B, Smeitink J.

Eur J Pediatr. 2003 Oct;162(10):714-8. Epub 2003 Aug 19.

PubMed [citation]
PMID:
12925875

A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency.

Odièvre MH, Chretien D, Munnich A, Robinson BH, Dumoulin R, Masmoudi S, Kadhom N, Rötig A, Rustin P, Bonnefont JP.

Hum Mutat. 2005 Mar;25(3):323-4. Review.

PubMed [citation]
PMID:
15712224

Details of each submission

From OMIM, SCV000032982.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In a patient with dihydrolipoamide dehydrogenase deficiency (DLDD; 246900), Grafakou et al. (2003) identified heterozygosity for 2 mutations in the DLD gene: an ile393-to-thr (I393T) substitution in exon 11, postulated to interfere with protein dimerization, and an IVS9+1G-A change at a consensus splice site (238331.0008). I393T corresponds to I358T in the mature protein (Odievre et al., 2005). The I358T mutation cosegregated with a polymorphism, 1422A-C, in exon 13; both appeared to be homozygous in cDNA studies, suggesting that the mRNA product of the splice site mutation was unstable. One year after presentation, the patient developed a stroke-like episode, and brain MRI showed symmetric hyperintensity consistent with Leigh syndrome (256000).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 1, 2021

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