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Intellectual disability

Gene: RORA

Green List (high evidence)

RORA (RAR related orphan receptor A)
EnsemblGeneIds (GRCh38): ENSG00000069667
EnsemblGeneIds (GRCh37): ENSG00000069667
OMIM: 600825, Gene2Phenotype
RORA is in 6 panels

2 reviews

Louise Daugherty (Genomics England Curator)

Comment on list classification: New gene suggested by external reviewer and reviewed by curation team. More than three affected individuals from unrelated families reported with at least 5 variants in this gene being reported, Intellectual disability was reported in the majority of cases and is a main feature of the phenotype. Publications support gene-disease association and rating of this gene to Green.
Created: 31 Oct 2018, 3 p.m.

Konstantinos Varvagiannis (Other)

I don't know

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, 10:48 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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
Phenotypes
  • Intellectual developmental disorder with or without epilepsy or cerebellar ataxia, 618060
OMIM
600825
Clinvar variants
Variants in RORA
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

31 Oct 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: rora has been classified as Green List (High Evidence).

18 Aug 2018, Gel status: 0

Added New Source

Konstantinos Varvagiannis (Other)

RORA was added to Intellectual disability panel. Sources: Literature

18 Aug 2018, Gel status: 0

Created

Konstantinos Varvagiannis (Other)

RORA was created by Konstantinos Varvagiannis