Early onset or syndromic epilepsy

Gene: PLPBP

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)

Previously called PROSC. AR early onset vitamin B6-dependent epilepsy - onset of seizures in neonatal period - favourable response to treatment with activated vit B6. Darin et al, 2016 - 3 patients from a consang Syrian family and 4 unrelated additional patients with infantile onset seizures. Identified hom/compound het mutations in the PROSC/PLPBP gene. Plecko 2017 - 4 further unrelated patients harbouring a total of 6 mutations including 4 novel. Tremino et al, 2018 has done functional studies on some of these variants.

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
Epilepsy, early-onset, vitamin B6-dependent, 617290

Publications

• 27912044
• 28391250

Comments from Eleanor Williams (Genomics England Curator), 4 Dec 2018 on the PROSC gene entry: Associated with Epilepsy, early-onset, vitamin B6-dependent in OMIM and Gene2Phenotype (probable). PMID: 27912044 (Darin et al, 2016): 7 patients from 5 unrelated families (4 different populations) with early-onset vitamin B6-dependent epilepsy were identified with homozygous or compound heterozygous mutations in the PROSC gene. Inheritance pattern consistent with biallelic pattern of inheritance. Seizures observed in all patients. Functional analyses of fibroblasts from 2 patients showed decreased or no PROSC expression.

Created: 18 Dec 2018, 12:20 p.m.

Green List (high evidence)

New gene name tag added PROSC should be approved HGNC gene symbol PLPBP. Pyridoxal phosphate-responsive epilepsy (PNPO associated) is rare form of autosomal recessive neonatal epileptic encephalopathy. Darin et al. (2016) PMID:27912044 reported that the five individuals with PROSC mutations all affected infants presented with seizures on day 1 of life, apart from subject 7, who presented at 1 month of age. Clinical characteristics of all five individuals all were noted as showing learning difficulties in addition to three with motor delay and four with speech delay. There are sufficient cases, and the phenotype, although complex, is relevant to this panel. On review with the internal clinical team it was thought that although vitamin B 6 abnormalities are currently in the exclusion criteria for the Epileptic encephalopathy panel, as it is treatable and has a good phenotypic fit it should still be included.

Created: 31 Oct 2017, 3:05 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Epilepsy, early-onset, vitamin B6-dependent, 617290

Publications

• 27912044