Parkinson Disease and Complex Parkinsonism
Gene: TUBB4A
Monoallelic mutations (de novo) cause hypomyelinating leukodystrophy 6. The phenotypic spectrum characterized by MRI findings range from hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) at the severe end to isolated hypomyelination at the mild end. Progressive neurologic findings reflect involvement of the pyramidal tracts (spasticity, brisk deep tendon reflexes, and Babinski sign), extrapyramidal system (rigidity, dystonia, choreoathetosis, oculogyric crisis, and perioral dyskinesia), cerebellum (ataxia, intention tremor, dysmetria), and bulbar function (dysarthria, dysphonia, and swallowing). Cognition is variably affected and usually less severely than motor function. Typically, those with H-ABC present in early childhood (ages one to three years) and those with isolated hypomyelination in later childhood or adulthood. The rate of progression varies with disease severity. PMID: 27809427 (gene review). Monoallelic mutations also cause Dystonia (DYT4) laryngeal dysphonia or whispering dysphonia (also known as DYT4 dystonia), in which brain MRI is normal. Keep this gene in both this gene to both the dystonia panel and pd (complex parkinsonism). Discuss any potentially pathogenic result with clinician and considering MRI. Also consider adding to the hsp panel (can present as complex hsp, PMID: 26477786)Created: 14 Dec 2016, 5:27 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications
Comment on list classification: Promoted from amber to green due to expert review.Created: 15 Dec 2016, 9:02 a.m.
Comment on list classification: Unsure whether this should be included on this panel. See comments regarding this gene on the early onset dystonia panel.Created: 2 Nov 2016, 5 p.m.
Comment on list classification: 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, 11:56 a.m.
19th Dec 2016: panel revised according to expert review and further curation.
This gene has been classified as Green List (High Evidence).
Phenotypes for TUBB4A were set to Complex parkinsonism;Dystonia; ?Dystonia 4, torsion, autosomal dominant, 128101; hereditary whispering dysphonia; Dystonia; hypomyelinating leukodystrophy 6
Phenotypes for TUBB4A were set to Dystonia; ?Dystonia 4, torsion, autosomal dominant, 128101; hereditary whispering dysphonia; Dystonia;hypomyelinating leukodystrophy 6
Publications for TUBB4A were set to 27809427
This gene has been classified as Green List (High Evidence).
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Green List (High Evidence).
TUBB4A was added to Parkinson Disease and Complex Parkinsonismpanel. Sources: Expert list
TUBB4A was created by ellenmcdonagh