Early onset or syndromic epilepsy
Gene: PCCA
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 and Helen Lord. 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
AR propionicacidemia - episodic vomiting, lethargy and ketosis, neutropenia, periodic thrombocytopenia, hypogammaglobulinemia, developmental reardation and an intolerance to protein, can also seizures. Gene Reviews - Shchelochkov et al, 2012 - Reported in 13-53% and EEG abnormalities seen in 40-63% of individuals wih PA. Alghamdi et al, 2018 - 14 PA patients from Saudi - 6/14 developed seizures mainly focal 12/14 have hom missese variants in PCCA 10 havre the same change Gly142Asp. 2/14 hom fs variant in PCCB gene (1/2 of these patients had seizures).Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Propionicacidemia, 606054
Publications
Comment on list classification: Promoted to green on the basis that there are sufficient cases of variants in this gene in patients with a relevant phenotype, and that seizures are reported in 12-53% of patients.Created: 4 Dec 2018, 3:01 p.m.
PCCA, along with PCCB, is associated with Propionicacidemia in OMIM and Gene2phenotype. >3 variants have been reported in PCCA in patients with Propionicacidemia. The incidence of seizures in patients with Propionicacidemia (which could be a result of variants in either gene) is 12-53% (Shchelochkov et al 2012 - GeneReviews - PMID: 22593918)
AlGhamdi et al 2018 (PMID: 30014764) report 10 patients from Saudi Arabia all with the same homozygous missense mutation in the PCCA gene (c.425G>A; p. Gly142Asp). 5 of these patients had seizures.Created: 20 Nov 2018, 1:35 p.m.
Seizures are part of the phenotype of this metabolic disorder.Created: 18 Aug 2018, 9:14 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Propionicacidemia, MIM#606054
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to PCCA.
Source NHS GMS was added to PCCA.
Zornitza Stark: Seizures are part of the pheno
Gene: pcca has been classified as Green List (High Evidence).
Publications for gene: PCCA were set to 2213454; 25875215; 30014764
Phenotypes for gene: PCCA were changed from to Propionicacidemia 606054
Publications for gene: PCCA were set to
Mode of inheritance for gene: PCCA was changed from to BIALLELIC, autosomal or pseudoautosomal
Expert Review Amber was added to PCCA. Panel: Genetic Epilepsy Syndromes
PCCA was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
PCCA was created by Sarah Leigh