Early onset or syndromic epilepsy

Gene: PRODH

I don't know

As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber.

Created: 25 Nov 2019, 9:06 p.m. | Last Modified: 25 Nov 2019, 9:06 p.m.

Panel Version: 1.453

PMID:17412540 (Afenjar et al 2007) report 4 unrelated children and biallelic variants in PRODH. The authors note that 4 previous patients had been reported (Jacquet et al, 2002, 2003 and Raux et al 2007) and of the 8 total patients, 5 had epilepsy (plus febrile case), often severe with status epilepticus.

Created: 21 Nov 2019, 3:52 p.m. | Last Modified: 21 Nov 2019, 3:52 p.m.

Panel Version: 1.419

PMID:18197084 (Di Rosa et al., 2008) screened 4 unrelated Italian children all of whom presented with epilepsy and ID, and compound het/homozygous variants in PRODH. Functional tests to confirm the pathogenicity were not performed.

Created: 21 Nov 2019, 3:46 p.m. | Last Modified: 21 Nov 2019, 3:46 p.m.

Panel Version: 1.419

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: Amber.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

I don't know

AR hyperprolinemia type 1 (HYRPRO1). Seizures have been reported as a feature in this, however more likely to be picked up as part of the metabolism panel.

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
Hyperprolinemia, type I, 239500

Publications

• 12217952

Green List (high evidence)

Evidence for the association of PRODH variants with Hyperprolinemia, type I, OMIM; 239500 has been classified as Definitive by ClinGen Aminoacidopathy Gene Curation Expert Panel on 04/27/2021 (https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_5f28c677-a9b4-4bb3-9aed-14af97ad9896-2021-04-27T160000.000Z)

Created: 19 May 2022, 3:41 p.m. | Last Modified: 19 May 2022, 3:41 p.m.

Panel Version: 2.524

Inclusion of this as a green gene on this panel is appropriate, based on the review in the Undiagnosed metabolic disorders panel and the views of clinical expert, Dr Arianna Tucci, UCL.

Created: 20 Mar 2017, 11:16 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hyperprolinemia, type I 239500