Large-scale TUBB4A mutational screening in isolated dystonia and controls
Michael Zech1, Sylvia Boesch2, Angela Jochim3
1Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; Institut für Neurogenomik, Helmholtz Zentrum München, Munich, Germany.
Parkinsonism & Related Disorders
|August 31, 2015
Summary
Mutations in the TUBB4A gene are not a common cause of isolated dystonia. This study found no evidence linking TUBB4A mutations to this condition in a large patient cohort.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- Mutations in the TUBB4A gene are linked to DYT4-isolated dystonia and hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC).
- While TUBB4A mutations are confirmed in H-ABC, their role in isolated dystonia is unclear.
Purpose of the Study:
- To investigate the role of TUBB4A gene mutations in isolated dystonia.
- To screen a large cohort of isolated dystonia patients for TUBB4A coding region variations.
Main Methods:
- Sanger sequencing and high-resolution melting analysis of TUBB4A coding regions in 709 isolated dystonia patients and 376 controls.
- Assessment of rare non-synonymous TUBB4A genetic variation frequency using the Exome Aggregation Consortium (ExAC) dataset.
Main Results:
- No pathogenic TUBB4A sequence alterations were identified in isolated dystonia patients or controls.
- The overall prevalence of rare missense and loss-of-function TUBB4A alleles is approximately 1:706, according to ExAC data.
Conclusions:
- TUBB4A coding mutations are unlikely to be a significant factor in the majority of isolated dystonia cases.
- Isolated dystonia, as observed in DYT4, may represent a rare manifestation within the broader spectrum of TUBB4A-related disorders.
