Early onset dystonia
Gene: TOR1AComment on mode of inheritance: Dystonia association with monoallelic variants is well-established with multiple cases reported worldwide (OMIM:128100). Biallelic variants cause a more severe phenotype of congenital arthrogryposis (OMIM:618947) and movement impairments including dystonia are also common (PMIDs: 29053766, 30244176). For this reason the MOI was updated from 'monoallelic' only to 'both mono- and biallelic (biallelic more severe)'.Created: 28 Mar 2022, 2:07 p.m. | Last Modified: 28 Mar 2022, 2:07 p.m.
Panel Version: 1.112
Comment from the Parkinson panel: Monoallelic mutations cause primary torsion dystonia (DYT1), early-onset isolated dystonia, plus plus childhood/adolescence onset, plus plus focal (but can be generalized). No other neurologic abnormalities are present. Disease severity varies considerably even within the same family. Isolated writer's cramp may be the only sign. One common mutation (c.907_909delGAG). Reduced penetrance. PMID 20301665 (gene review). Consider moving this gene to the dystonia panel?Created: 15 Dec 2016, 11:11 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
primary torsion dystonia (DYT1), early-onset isolated dystonia
Publications
Evidence for incomplete penetrance in several studies, and a modifier variant that may influence penetrance: PMID: 9288096;16537570;17503336;11523564.Created: 25 Aug 2016, 10:35 a.m.
Is on the Complex Parkinson's Disease/Dystonia NGS Panel in the UCLH National Hospital for Neurology and Neurosurgery & Institute of Neurology (NHNN) Neurogenetics genetic testing manual.Created: 10 Jun 2016, 8:59 a.m.
Comment on list classification: Should remain green due to information within the UCLH National Hospital for Neurology and Neurosurgery & Institute of Neurology (NHNN) Neurogenetics genetic testing manual for dystonia.Created: 10 Jun 2016, 7:22 a.m.
Was submitted as "DYT1" by expert.Created: 16 Jul 2015, 1:37 p.m.
Phenotypes for gene: TOR1A were changed from Dystonia-1, torsion, OMIM:128100; Dystonic disorder, MONDO:0003441 to Dystonia-1, torsion, OMIM:128100; Arthrogryposis multiplex congenita 5, OMIM:618947
Mode of inheritance for gene: TOR1A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: TOR1A were changed from Early-Onset Primary Dystonia; Dystonia-1, torsion, 128100; Autosomal dominant or sporadic dystonia (DYT1) to Dystonia-1, torsion, OMIM:128100; Dystonic disorder, MONDO:0003441
Publications for TOR1A were set to http://www.ncbi.nlm.nih.gov/books/NBK1155/; 9288096; 16537570; 17503336; 11523564;20301665
17th Oct 2016: Promoted to version 1. The panel was revised after expert input and internal discussion with the clinical team. Other panels such as hereditary ataxia or dementia may be applied in conjunction with this panel where appropriate for genome analysis.
Publications for TOR1A were set to http://www.ncbi.nlm.nih.gov/books/NBK1155/;9288096;16537570;17503336;11523564
Phenotypes for TOR1A were set to Early-Onset Primary Dystonia; Dystonia-1, torsion, 128100; Autosomal dominant or sporadic dystonia (DYT1)
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Publications for TOR1A were set to http://www.ncbi.nlm.nih.gov/books/NBK1155/
Mode of inheritance for TOR1A was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
TOR1A was added to Early onset dystoniapanel. Sources: Eligibility statement prior genetic testing
Model of inheritance for gene TOR1A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Model of inheritance for gene TOR1A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Model of inheritance for gene TOR1A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Model of inheritance for gene TOR1A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Model of inheritance for gene TOR1A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Model of inheritance for gene TOR1A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Model of inheritance for gene TOR1A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Model of inheritance for gene TOR1A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Model of inheritance for gene TOR1A was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
TOR1A was added to Early onset dystoniapanel. Sources: Expert
TOR1A was added to Early onset dystoniapanel. Sources: Emory Genetics Laboratory
TOR1A was added to Early onset dystoniapanel. Sources: Radboud University Medical Center, Nijmegen
TOR1A was added to Early onset dystoniapanel. Sources: UKGTN
TOR1A was added to Early onset dystoniapanel. Sources: Illumina TruGenome Clinical Sequencing Services