AJ298105.1:g.61273_107768delins6086 AND Pyruvate dehydrogenase E3-binding protein deficiency

Clinical significance:Pathogenic (Last evaluated: Feb 1, 2007)

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:
RCV000002198.3

Allele description [Variation Report for AJ298105.1:g.61273_107768delins6086]

AJ298105.1:g.61273_107768delins6086

Gene:
PDHX:pyruvate dehydrogenase complex component X [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
11p13
Preferred name:
AJ298105.1:g.61273_107768delins6086
HGVS:
AJ298105.1:g.61273_107768delins6086
Note:
46-kb deletion spanning exons 3-9 of PDHX plus flanking intronic sequences, created by the insertion of an LINE-1 (L1) element.
Nucleotide change:
46-KB DEL
Links:
OMIM: 608769.0007

Condition(s)

Name:
Pyruvate dehydrogenase E3-binding protein deficiency (PDHXD)
Synonyms:
LACTIC ACIDEMIA DUE TO DEFECT IN LIPOYL-CONTAINING COMPONENT X OF THE PYRUVATE DEHYDROGENASE COMPLEX; PYRUVATE HYDROGENASE E3-BINDING PROTEIN DEFICIENCY; E3-Binding Protein (Component X) Deficiency
Identifiers:
MONDO: MONDO:0009503; MedGen: C1855553; OMIM: 245349

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000022356OMIMno assertion criteria providedPathogenic
(Feb 1, 2007)
germlineliterature only

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

Summary from all submissions

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

Citations

PubMed

A large genomic deletion in the PDHX gene caused by the retrotranspositional insertion of a full-length LINE-1 element.

Miné M, Chen JM, Brivet M, Desguerre I, Marchant D, de Lonlay P, Bernard A, Férec C, Abitbol M, Ricquier D, Marsac C.

Hum Mutat. 2007 Feb;28(2):137-42.

PubMed [citation]
PMID:
17152059

Details of each submission

From OMIM, SCV000022356.2

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

Description

In a 25-year-old man with pyruvate dehydrogenase E3-binding protein deficiency (PDHXD; 245349), Mine et al. (2007) identified compound heterozygosity for a 46-kb deletion (nucleotides 61273 to 107768) and a 742C-T transition in exon 6 of the PDHX gene, resulting in a gln248-to-ter (Q248X; 608769.0008) substitution. The 46-kb deletion combined with the integration of a full-length LINE-1 (L1) element in the PDHX gene. PCR and sequencing showed that the deduced bottom and top strand cleavage sites coincided with the consensus L1 endonuclease target sequence, while the full-length L1 element was followed by a poly(A) tail. Mine et al. (2007) suggested a model of 'template jumping' as a mechanism for retrotranspositional insertion of the full-length L1 element. This mutant allele was inherited from the patient's unaffected mother, and the Q248X mutation was inherited from the patient's father. Clinically, the patient showed psychomotor delay associated with spastic diplegia and dysarthria at age 3 years. At 7 years, he had recurrent acute dystonic posturing, which disappeared with a ketogenic diet. Serum lactate was normal, but CSF lactate and pyruvate were increased. Brain MRI showed atrophic corpus callosum and hyperintensities in the putamen. PDH complex activity in fibroblasts and lymphocytes was 19% and 30% of normal values, respectively. Western blot analysis detected no E3-binding protein. Mine et al. (2007) noted that the L1 retrotransposition found in this patient reveals a novel mechanism causing human genetic disease.

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

Last Updated: Oct 7, 2021

Support Center