Childhood onset dystonia, chorea or related movement disorder

Gene: GNB1

Green List (high evidence)

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

Created: 14 Mar 2022, 10:59 a.m. | Last Modified: 14 Mar 2022, 10:59 a.m.

Panel Version: 1.217

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

Created: 3 Mar 2022, 4:45 p.m. | Last Modified: 3 Mar 2022, 4:45 p.m.

Panel Version: 1.212

Comment on mode of pathogenicity: Gen2Phen entry for GNB1 (https://www.ebi.ac.uk/gene2phenotype/gfd?dbID=2121) lists the mutation consequence summary as Activating

Created: 14 Sep 2021, 6:01 p.m. | Last Modified: 14 Sep 2021, 6:01 p.m.

Panel Version: 1.152

Hemati et al (2018)(PMID: 30194818) reviewed 46 pathognic GNB1 variants in cases with Mental retardation, autosomal dominant 42 (OMIM:616973). They reported early hypotonia leading to hypertonia and spasticity in >75% of cases.

Created: 14 Sep 2021, 12:56 p.m. | Last Modified: 14 Sep 2021, 12:56 p.m.

Panel Version: 1.147

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

Created: 14 Sep 2021, 12:17 p.m. | Last Modified: 14 Sep 2021, 12:17 p.m.

Panel Version: 1.147

Green List (high evidence)

Two reports of unrelated patients with a similar phenotype - Predominant movement disorder - Myoclonus dystonia, with intellectual disability, early childhood onset with slow progression and impaired vertical eye movements. No epilepsy in these patients

Created: 16 Sep 2020, 6:31 a.m. | Last Modified: 16 Sep 2020, 6:31 a.m.

Panel Version: 1.51

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Myoclonus; Dystonia; Childhood onset dystonia; Intellectual disability

Publications

• 31034681
• 27668284

Mode of pathogenicity
Other

Green List (high evidence)

Multiple reports of dystonia in this disorder. In a recent series of 18 individuals with de novo mutations, the most observed substitution affected the p.Ile80 residue in exon 6, with 28% of individuals carrying a variant at this residue. Dystonia and growth delay were observed more frequently in individuals carrying variants in this residue, suggesting a potential genotype-phenotype correlation.
Sources: Expert list

Created: 5 Sep 2020, 8:31 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Mental retardation, autosomal dominant 42, MIM# 616973

Publications

• 27108799
• 30194818
• 27668284
• 31034681

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