Adult onset neurodegenerative disorder

Gene: TUBB4A

Comment 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 128101

Created: 29 Mar 2021, 12:51 p.m. | Last Modified: 29 Mar 2021, 12:51 p.m.

Panel Version: 2.172

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

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

• 25374358

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

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.

Green List (high evidence)

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