Early onset or syndromic epilepsy
Gene: PDHA1
Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor. Suggested gene rating: Green.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
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, 312170
Publications
Comment when marking as ready: Sufficient cases.Created: 20 Nov 2018, 5:36 p.m.
Comment on list classification: > 3 cases of patients with variants in this gene with Pyruvate dehydrogenase E1-alpha deficiency and with seizures as part of the phenotype.Created: 20 Nov 2018, 5:34 p.m.
Comment on mode of inheritance: Heterozygous mutations seen in females showing phenotype.Created: 20 Nov 2018, 5:29 p.m.
Comment on phenotypes: Seizures are listed as part of the phenotype for X-LINKED LEIGH SYNDROME, PYRUVATE DEHYDROGENASE E1-ALPHA DEFICIENCY IN FEMALES and INTELLECTUAL DISABILTIY in Gene2PhenotypeCreated: 20 Nov 2018, 5:27 p.m.
PDHA1 is associated with Pyruvate dehydrogenase E1-alpha deficiency in OMIM and PYRUVATE DEHYDROGENASE E1-ALPHA DEFICIENCY IN FEMALES, X-LINKED LEIGH SYNDROME and INTELLECTUAL DISABILTIY in Gene2Phenotype.
Lissens et al 1996 (PMID: 8664900) - patient 2 (female) reported to have seizures and a variant resulting in R302C in PDHA1.
Lissens et al 2000 (PMID: 10679936) - summarizes the multiple variants in PDHA1 found in patients with phenotypes including epilepsy.Created: 20 Nov 2018, 5:23 p.m.
XLD. Seizures are part of the phenotype of this metabolic disorder.Created: 18 Aug 2018, 10:12 a.m.
Mode of inheritance
Other
Phenotypes
Pyruvate dehydrogenase E1-alpha deficiency, MIM#312170
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to PDHA1.
Source NHS GMS was added to PDHA1.
Zornitza Stark: XLD. Seizures are part of the
Gene: pdha1 has been classified as Green List (High Evidence).
Gene: pdha1 has been classified as Green List (High Evidence).
Mode of inheritance for gene: PDHA1 was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: PDHA1 were changed from to Pyruvate dehydrogenase E1-alpha deficiency 312170; X-LINKED LEIGH SYNDROME; PYRUVATE DEHYDROGENASE E1-ALPHA DEFICIENCY IN FEMALES; INTELLECTUAL DISABILTIY
Publications for gene: PDHA1 were set to
Expert Review Amber was added to PDHA1. Panel: Genetic Epilepsy Syndromes
PDHA1 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
PDHA1 was created by Sarah Leigh