Early onset or syndromic epilepsy

Gene: PDHA1

I don't know

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

Green List (high evidence)

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

• 27896109

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 Gene2Phenotype

Created: 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.

Green List (high evidence)

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