Early onset or syndromic epilepsy
Gene: RORA
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
AD Intellectual dev disorder with or without epilepsy or cerebellar ataxia. Guissart et al 2018 - 11 unrelated patients with syndromic intellectual disability - 7 had seizures of variable types - het mutations in RORA gene - functional work undertaken.Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Intellectual developmental disorder with or without epilepsy or cerebellar ataxia, 618060
Publications
Comment when marking as ready: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 5 variants reported in unrelated cases.Created: 26 Sep 2018, 9:49 a.m.
Multiple affected individuals from unrelated families reported with variants in this gene and neurodevelopmental phenotypes, seizures are part of the phenotype.Created: 20 Aug 2018, 10:44 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications
PMID 29656859 describes a cohort of 16 individuals from 13 families with different heterozygous RORA variants, including : 2 de novo intergenic microdeletions, 1 intragenic microdeletion, 1 de novo disrupting microduplication and nine de novo point mutations (3 truncating, 1 splice-site, 5 missense SNVs). Intellectual disability (ID) was an almost universal feature with the exception of 1 individual who however had a diagnosis of ASD. Seizures were reported in 11 (of 16 individuals). Despite the small size of their cohort, the authors propose 2 subgroups of patients, the first due to haploinsufficiency presenting with ID and autistic features and the other due to a presumed dominant toxic effect, characterized by ID, gait ataxia and cerebellar atrophy. The phenotype of ID segregated with the deletion (as well as with an intragenic DISC1 deletion) in the family reported. Mutant mice (homozygous for a Rora deletion) display gait ataxia and degeneration of cerebellar Purkinje cells. Zebrafish functional studies, support an effect in the developing cerebellum, similar to what is observed in humans. This is the first report of the RORA-related phenotypes. As a result this gene could be considered for inclusion in the panel as amber or green.Created: 18 Aug 2018, 10:46 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Intellectual developmental disorder with or without epilepsy or cerebellar ataxia, 618060
Publications
Source Wessex and West Midlands GLH was added to RORA.
Source NHS GMS was added to RORA.
Konstantinos Varvagiannis: PMID 29656859 describes a coho
Gene: rora has been classified as Green List (High Evidence).
Gene: rora has been classified as Green List (High Evidence).
RORA was added to Genetic Epilepsy Syndromes panel. Sources: Literature
RORA was created by Konstantinos Varvagiannis