Adult onset neurodegenerative disorder
Gene: TUBB4AComment on phenotypes: Previous phenotypes:
Leukodystrophy, hypomyelinating, 6 612438;?Dystonia 4, torsion, autosomal dominant, 128101;hypomyelinating leukodystrophy 6;Implicated autosomal dominant variants in two families with ataxia;Dystonia;Torsion dystonia 4 (128101) - some individuals with ataxia;ataxia;hereditary whispering dysphonia;Complex parkinsonism;hypomyelinating leukodystrophy 6 (612438) - ataxia reported.;Dystonia 4, torsion, autosomal dominant 128101Created: 29 Mar 2021, 12:51 p.m. | Last Modified: 29 Mar 2021, 12:51 p.m.
Panel Version: 2.172
Hypomyelinating leukodystrophy-6, also known as hypomyelinating leukodystrophy with atrophy of the basal ganglia and cerebellum, is a neurologic disorder characterized by onset in infancy or early childhood -red. Dystonia-4, also known as whispering dysphonia, is an autosomal dominant neurologic disorder characterized by onset in the second to third decade of progressive laryngeal dysphonia - not sure if sufficent cases have been reported with definitely pathogenic variants. Amber?Created: 2 Sep 2019, 4:06 p.m. | Last Modified: 2 Sep 2019, 4:06 p.m.
Panel Version: 1.99
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Leukodystrophy, hypomyelinating, 6 612438; ?Dystonia 4, torsion, autosomal dominant, 128101; hypomyelinating leukodystrophy 6; Implicated autosomal dominant variants in two families with ataxia; Dystonia; Torsion dystonia 4 (128101) - some individuals with ataxia; ataxia; hereditary whispering dysphonia; Complex parkinsonism; hypomyelinating leukodystrophy 6 (612438) - ataxia reported.; Dystonia 4, torsion, autosomal dominant 128101
Evidence for an association with ALSCreated: 23 Jul 2019, 3:35 p.m. | Last Modified: 23 Jul 2019, 3:35 p.m.
Panel Version: 1.72
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications
Variants in this GENE are reported as part of current diagnostic practice
As discussed with the GMS Neurology Specialist Test Group webex call 11th September 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene AmberCreated: 20 Sep 2019, 4:19 p.m. | Last Modified: 20 Sep 2019, 4:19 p.m.
Panel Version: 1.106
Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group. All the green and amber, except for the genes with triplet repeats, were reviewed.Created: 2 Sep 2019, 4:46 p.m. | Last Modified: 2 Sep 2019, 4:46 p.m.
Panel Version: 1.101
Review and rating submitted by Nick Beauchamp (Sheffield Diagnostic genetics Service), on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group.Created: 23 Jul 2019, 3:51 p.m. | Last Modified: 23 Jul 2019, 3:51 p.m.
Panel Version: 1.74
Review and rating submitted byJames Polke (North Bristol NHS Trust), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group.Created: 23 Apr 2019, 5:35 p.m.
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: TUBB4A were changed from Leukodystrophy, hypomyelinating, 6 612438; ?Dystonia 4, torsion, autosomal dominant, 128101; hypomyelinating leukodystrophy 6; Implicated autosomal dominant variants in two families with ataxia; Dystonia; Torsion dystonia 4 (128101) - some individuals with ataxia; ataxia; hereditary whispering dysphonia; Complex parkinsonism; hypomyelinating leukodystrophy 6 (612438) - ataxia reported.; Dystonia 4, torsion, autosomal dominant 128101 to Leukodystrophy, hypomyelinating, 6, OMIM:612438; Dystonia 4, torsion, autosomal dominant, OMIM:128101
Source Expert Review Amber was added to TUBB4A. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Source Wessex and West Midlands GLH was added to TUBB4A.
Publications for gene TUBB4A were changed from PMID: 25497598; 27809427 to 25374358; 27809427; 25497598
Source Yorkshire and North East GLH was added to TUBB4A.
Source NHS GMS was added to TUBB4A.
Source London North GLH was added to TUBB4A.
Louise Daugherty: Comment on phenotypes: amended
Mode of pathogenicity for gene: TUBB4A was changed from to Other
Added phenotypes hypomyelinating leukodystrophy 6; Dystonia; Complex parkinsonism; hereditary whispering dysphonia; ?Dystonia 4, torsion, autosomal dominant, 128101 for gene: TUBB4A
Added phenotypes Dystonia 4, torsion, autosomal dominant 128101; ataxia; Leukodystrophy, hypomyelinating, 6 612438 for gene: TUBB4A
Added phenotypes Implicated autosomal dominant variants in two families with ataxia; Torsion dystonia 4 (128101) - some individuals with ataxia; hypomyelinating leukodystrophy 6 (612438) - ataxia reported. for gene: TUBB4A
gene: TUBB4A was added gene: TUBB4A was added to Neurodegenerative disorders - adult onset. Sources: Expert Review Green Mode of inheritance for gene: TUBB4A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: TUBB4A were set to PMID: 25497598; 27809427 Phenotypes for gene: TUBB4A were set to Dystonia; hereditary whispering dysphonia; ?Dystonia 4, torsion, autosomal dominant, 128101