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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Mutations in the autoregulatory domain of β-tubulin 4a cause hereditary dystonia
Annals of Neurology, Volume 73, No. 4, Year 2013
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Description
Dystonia type 4 (DYT4) was first described in a large family from Heacham in Norfolk with an autosomal dominantly inherited whispering dysphonia, generalized dystonia, and a characteristic hobby horse ataxic gait. We carried out a genetic linkage analysis in the extended DYT4 family that spanned 7 generations from England and Australia, revealing a single LOD score peak of 6.33 on chromosome 19p13.12-13. Exome sequencing in 2 cousins identified a single cosegregating mutation (p.R2G) in the β-tubulin 4a (TUBB4a) gene that was absent in a large number of controls. The mutation is highly conserved in the β-tubulin autoregulatory MREI (methionine-arginine-glutamic acid-isoleucine) domain, highly expressed in the central nervous system, and extensive in vitro work has previously demonstrated that substitutions at residue 2, specifically R2G, disrupt the autoregulatory capability of the wild-type β-tubulin peptide, affirming the role of the cytoskeleton in dystonia pathogenesis. © 2013 American Neurological Association.
Authors & Co-Authors
Hersheson, Joshua
United Kingdom, London
National Hospital for Neurology and Neurosurgery
Mencacci, Niccolò Emanuele
United Kingdom, London
National Hospital for Neurology and Neurosurgery
Italy, Milan
Università Degli Studi Di Milano
Davis, Mary
United Kingdom, London
National Hospital for Neurology and Neurosurgery
MacDonald, Nicola
United Kingdom, London
University College London Hospitals Nhs Foundation Trust
Trabzuni, Daniah
United Kingdom, London
National Hospital for Neurology and Neurosurgery
Saudi Arabia, Riyadh
King Faisal Specialist Hospital and Research Centre
Ryten, Mina
United Kingdom, London
National Hospital for Neurology and Neurosurgery
Pittman, Alan Michael
United Kingdom, London
National Hospital for Neurology and Neurosurgery
Paudel, Reema
United Kingdom, London
National Hospital for Neurology and Neurosurgery
Kara, Eleanna
United Kingdom, London
National Hospital for Neurology and Neurosurgery
Fawcett, Katherine
United Kingdom, London
National Hospital for Neurology and Neurosurgery
Plagnol, Vincent
United Kingdom, London
National Hospital for Neurology and Neurosurgery
Bhatia, Kailash P.
United Kingdom, London
National Hospital for Neurology and Neurosurgery
Medlar, Alan J.
United Kingdom, London
University College London
Stanescu, Horia C.
United Kingdom, London
University College London
Hardy, John A.
United Kingdom, London
National Hospital for Neurology and Neurosurgery
Kleta, Robert
United Kingdom, London
University College London
Wood, Nick William
United Kingdom, London
National Hospital for Neurology and Neurosurgery
Houlden, Henry H.
United Kingdom, London
National Hospital for Neurology and Neurosurgery
Statistics
Citations: 161
Authors: 18
Affiliations: 5
Identifiers
Doi:
10.1002/ana.23832
ISSN:
03645134
e-ISSN:
15318249
Research Areas
Cancer
Genetics And Genomics