Early onset or syndromic epilepsy

Gene: RYR3

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: Red.

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

Panel Version: 1.189

Red List (low evidence)

Not associated with a phenotype on OMIM. Reviews from panel app: Euro epinomics-res consortium, 2014 - 356 trios with classic EIEE - 2 de novo variants in RYR3 identified, they say in the paper that this provides suggestive evidence for this gene. Peng et al, 2018 - 56 Chinese families with West syndrome (classic form of EIEE) - AR - 2 diff missense variants identified.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
Unknown

Phenotypes
Unkown

Green List (high evidence)

Comment on publications: PMID: 39220738 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.

Created: 18 Mar 2025, 12:40 p.m. | Last Modified: 18 Mar 2025, 12:40 p.m.

Panel Version: 7.70

Previously there have been four reports of seizures in patients with biallelic RYR3 variants (PMID: 25262651; 29667327; 39220738). Using a cohort of patients with idiopathic(non-lesional) partial epilepsy/susceptibility of seizures, authors of PMID: 39840699 report thirteen RYR3 variants in seven cases. In all but one of the cases, the variants are compound heterozygotes, with the remaining case having a de novo heterozygous RYR3 variant. Seizure onset was in childhood (1 to 7 years), brain MRIs were normal in all cases, there was no evidence of myopathy and there was a single case of intellectual disability (table 1, PMID: 39840699).

Created: 18 Mar 2025, 12:27 p.m. | Last Modified: 18 Mar 2025, 12:27 p.m.

Panel Version: 7.67

Comment when marking as ready: Not associated with phenotype in OMIM (lasted edited 01/25/2005) or in Gen2Phen. Four variants reported in four cases, but with little supportive evidence for association with Epileptic encephalopathy.

Created: 8 Nov 2018, 1:40 p.m.

Comment on mode of inheritance: MOI based on report in PMID 29667327

Created: 8 Nov 2018, 12:43 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
idiopathic(non-lesional) partial epilepsy/susceptibility of seizures

Red List (low evidence)

Publications

• EuroEPINOMICS-RES Consortium (2014) AJHG 95:1-11

Red List (low evidence)

Publications

• EuroEPINOMICS-RES Consortium (2014) AJHG 95:1-11

Red List (low evidence)

Publications

• EuroEPINOMICS-RES Consortium (2014) AJHG 95:1-11

Red List (low evidence)

Publications

• EuroEPINOMICS-RES Consortium (2014) AJHG 95:1-11

Gene added in expert review of the panel by Richard Scott (Genomics England), Manju Kurian (UCL-Institute of Child Health), Natalie Trump (NHS - Great Ormond Street Hospital), Amy McTague (UCL Institute of Child Health).

Created: 12 Nov 2015, 4:21 p.m.