Genes in panel

Neurodegenerative disorders - adult onset

Gene: TUBB4A

Amber List (moderate evidence)

TUBB4A (tubulin beta 4A class IVa)
EnsemblGeneIds (GRCh38): ENSG00000104833
EnsemblGeneIds (GRCh37): ENSG00000104833
OMIM: 602662, Gene2Phenotype
TUBB4A is in 20 panels

4 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

I don't know

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

Nick Beauchamp (Sheffield Diagnostic Genetics Service)

Green List (high evidence)

Evidence for an association with ALS
Created: 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

Louise Daugherty (Genomics England Curator)

I don't know

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 Amber
Created: 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.

James Polke (Neurogenetics Laboratory, Institute of Neurology, London)

Green List (high evidence)

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Wessex and West Midlands GLH
  • Yorkshire and North East GLH
  • NHS GMS
  • London North GLH
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
OMIM
602662
Clinvar variants
Variants in TUBB4A
Penetrance
None
Publications
Mode of Pathogenicity
Other
Panels with this gene

History Filter Activity

20 Sep 2019, Gel status: 2

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Amber was added to TUBB4A. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)

2 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source Wessex and West Midlands GLH was added to TUBB4A.

23 Jul 2019, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene TUBB4A were changed from PMID: 25497598; 27809427 to 25374358; 27809427; 25497598

23 Jul 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source Yorkshire and North East GLH was added to TUBB4A.

23 Apr 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to TUBB4A.

23 Apr 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to TUBB4A.

25 Jan 2019, Gel status: 4

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

Louise Daugherty: Comment on phenotypes: amended

20 Dec 2018, Gel status: 4

Set mode of pathogenicity

Rebecca Foulger (Genomics England curator)

Mode of pathogenicity for gene: TUBB4A was changed from to Other

18 Dec 2018, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Added phenotypes hypomyelinating leukodystrophy 6; Dystonia; Complex parkinsonism; hereditary whispering dysphonia; ?Dystonia 4, torsion, autosomal dominant, 128101 for gene: TUBB4A

18 Dec 2018, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Added phenotypes Dystonia 4, torsion, autosomal dominant 128101; ataxia; Leukodystrophy, hypomyelinating, 6 612438 for gene: TUBB4A

18 Dec 2018, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

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

18 Dec 2018, Gel status: 4

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Rebecca Foulger (Genomics England curator)

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