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NC_000023.10:g.(?_18660114)_(19377781_?)del AND Pyruvate dehydrogenase E1-alpha deficiency

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 11, 2019
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001033913.1

Allele description

NC_000023.10:g.(?_18660114)_(19377781_?)del

Genes:
  • ADGRG2:adhesion G protein-coupled receptor G2 [Gene - OMIM - HGNC]
  • CDKL5:cyclin dependent kinase like 5 [Gene - OMIM - HGNC]
  • PHKA2:phosphorylase kinase regulatory subunit alpha 2 [Gene - OMIM - HGNC]
  • PPEF1:protein phosphatase with EF-hand domain 1 [Gene - OMIM - HGNC]
  • PDHA1:pyruvate dehydrogenase E1 subunit alpha 1 [Gene - OMIM - HGNC]
  • RS1:retinoschisin 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
Xp22.13-22.12
Genomic location:
ChrX: 18660114 - 19377781 (on Assembly GRCh37)
Preferred name:
NC_000023.10:g.(?_18660114)_(19377781_?)del
HGVS:
NC_000023.10:g.(?_18660114)_(19377781_?)del

Condition(s)

Name:
Pyruvate dehydrogenase E1-alpha deficiency (PDHAD)
Synonyms:
X-linked Leigh syndrome; ATAXIA, INTERMITTENT, WITH PYRUVATE DEHYDROGENASE DEFICIENCY; ATAXIA WITH LACTIC ACIDOSIS I; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010717; MedGen: C1839413; OMIM: 312170

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001197220Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 11, 2019) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Molecular characterization of 82 patients with pyruvate dehydrogenase complex deficiency. Structural implications of novel amino acid substitutions in E1 protein.

Imbard A, Boutron A, Vequaud C, Zater M, de Lonlay P, de Baulny HO, Barnerias C, Miné M, Marsac C, Saudubray JM, Brivet M.

Mol Genet Metab. 2011 Dec;104(4):507-16. doi: 10.1016/j.ymgme.2011.08.008. Epub 2011 Aug 18.

PubMed [citation]
PMID:
21914562

A 1.1 million base pair X-chromosomal deletion covering the PDHA1 and CDKL5 genes in a female patient with West syndrome and pyruvate oxidation deficiency.

Mayr JA, Koch J, Fauth C, Zimmermann FA, Rauscher C, Zschocke J, Sperl W.

Neuropediatrics. 2012 Jun;43(3):130-4. doi: 10.1055/s-0032-1309308. Epub 2012 Apr 2.

PubMed [citation]
PMID:
22473288
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001197220.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

A gross deletion of the genomic region encompassing the full coding sequence of the PDHA1 gene has been identified. The boundaries of this event are unknown as the deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. Isolated whole-gene deletions of PDHA1 have not been reported in the literature. However, larger copy number events that include this gene have been reported in the literature (PMID: 21914562, 20591708, 22473288). Loss-of-function variants in PDHA1 are known to be pathogenic (PMID: 10679936, 21914562). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Apr 23, 2022