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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\u201013. Exome sequencing in 2 cousins identified a single cosegregating mutation (p.R2G) in the \u03b2\u2010tubulin 4a (TUBB4a) gene that was absent in a large number of controls. The mutation is highly conserved in the \u03b2\u2010tubulin autoregulatory MREI (methionine\u2013arginine\u2013glutamic acid\u2013isoleucine) 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\u2010type \u03b2\u2010tubulin peptide, affirming the role of the cytoskeleton in dystonia pathogenesis. 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