Ataxia and cerebellar anomalies - narrow panel

Gene: RORA

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 5 Feb 2023, 5:18 p.m. | Last Modified: 5 Feb 2023, 5:18 p.m.

Panel Version: 3.30

Green List (high evidence)

Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least four variants reported in at least four cases with ataxia (PMID 29656859).

Created: 26 May 2021, 10:59 a.m. | Last Modified: 26 May 2021, 10:59 a.m.

Panel Version: 2.185

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 26 May 2021, 10:45 a.m. | Last Modified: 26 May 2021, 10:45 a.m.

Panel Version: 2.185

Green List (high evidence)

11 unrelated individuals with syndromic intellectual disability and de novo variants in this gene. Severity varied from mild borderline intellectual disability with mild speech delay or normal speech, through to severe cognitive impairment with poor or absent speech. Most had ataxia, hypotonia, poor coordination, and/or mild tremor, suggesting cerebellar dysfunction. Three individuals had documented cerebellar hypoplasia or pontocerebellar atrophy on brain imaging. Seven had seizures of variable types, including neonatal myoclonic, tonic-clonic, multifocal, generalized, and absence. Five were diagnosed with autism spectrum disorder. More variable features included strabismus, esotropia, nystagmus, and oculomotor apraxia. Postulated that some variants exert dominant-negative effect resulting in a more severe phenotype than the LoF variants.
Sources: Expert list

Created: 12 Sep 2020, 7:38 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Intellectual developmental disorder with or without epilepsy or cerebellar ataxia, MIM# 618060

Publications

• 29656859

Variants in this GENE are reported as part of current diagnostic practice