Early onset or syndromic epilepsy

Gene: PCCB

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 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

Green List (high evidence)

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

• 7386459

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, 3:02 p.m.

PCCB, along with PCCA, is associated with Propionicacidemia in OMIM and Gene2phenotype. >3 variants have been reported in PCCB 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 2 patients from Saudi Arabia with homozygous duplication in exon 11 of the PCCB gene (c.1050dupT p. E351X) . 1 of these patients had seizures.

Created: 20 Nov 2018, 4:33 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this metabolic disorder.

Created: 18 Aug 2018, 9:15 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