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Gene: PDHA1

Green List (high evidence)

PDHA1 (pyruvate dehydrogenase E1 alpha 1 subunit)
EnsemblGeneIds (GRCh38): ENSG00000131828
EnsemblGeneIds (GRCh37): ENSG00000131828
OMIM: 300502, Gene2Phenotype
PDHA1 is in 18 panels

3 reviews

Michelle Torres (Victorian Clinical Genetics Services)

Green List (high evidence)

Onset in infancy or early childhood (OMIM).

Variants in this gene are known to have variable expressivity which has been detailed by PMID: 22142326.
- Neonatal lactic acidosis predominates in males, in whom the degree of residual pyruvate dehydrogenase complex (PDHC) activity depends on the PDHA1 mutation.
- Very severe mutations are not found in males, probably because they are embryonically lethal.
- In heterozygous females, the residual PDHC activity is related to both the mutation and the random pattern of X‐inactivation, with variable expression of the mutant and normal genes in different tissues.
- Females can also present a severe clinical picture, with early‐onset microcephaly, spastic quadriplegia, severe epilepsy, and cortical/subcortical atrophy.
- In the milder form, individuals may show intercurrent clinical and biochemical normalization, despite persistence of neuroradiological and electrophysiological findings. Some late‐onset childhood variants respond to thiamine supplementation.
Created: 16 Jan 2025, 8:54 p.m. | Last Modified: 16 Jan 2025, 8:54 p.m.
Panel Version: 1.1064

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Pyruvate dehydrogenase E1-alpha deficiency MIM#312170

Publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Reports of familial recurrence suggest that some females are mildly or not clinically affected and just have reproductive risk of severely affected males/females.
Created: 17 Aug 2022, 6:40 a.m. | Last Modified: 17 Aug 2022, 6:40 a.m.
Panel Version: 0.131

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Pyruvate dehydrogenase E1-alpha deficiency (MIM#312170)

Crystle Lee (Victorian Clinical Genetics Services)

I don't know

Well-established gene disease association however condition shows XLD inheritance with a high proportion of females affected. Complete loss-of-function variants are embryonic lethal in males. Phenotype is highly variable

Does not fit with scope of testing (AR/XLR) - consider for exclusion
Created: 14 Jul 2022, 11:12 p.m. | Last Modified: 14 Jul 2022, 11:12 p.m.
Panel Version: 0.49

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Pyruvate dehydrogenase E1-alpha deficiency (MIM#312170)

Publications

History Filter Activity

2 Nov 2023, Gel status: 3

Set Phenotypes, Set publications

Seb Lunke (Victorian Clinical Genetics Services)

Added phenotypes Pyruvate dehydrogenase E1-alpha deficiency (MIM#312170) for gene: PDHA1 Publications for gene PDHA1 were updated from 28584645; 22142326 to 22142326; 28584645

17 Aug 2022, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: pdha1 has been classified as Green List (High Evidence).

17 Aug 2022, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: PDHA1 were changed from Pyruvate dehydrogenase E1-alpha deficiency to Pyruvate dehydrogenase E1-alpha deficiency (MIM#312170)

17 Aug 2022, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: PDHA1 were set to

17 Aug 2022, Gel status: 3

Removed Tag

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Tag for review was removed from gene: PDHA1.

15 Jul 2022, Gel status: 3

Added Tag

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Tag for review tag was added to gene: PDHA1.

1 Jun 2022, Gel status: 3

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: PDHA1 was added gene: PDHA1 was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: PDHA1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: PDHA1 were set to Pyruvate dehydrogenase E1-alpha deficiency