title: Pathogenic variants in TUBB4A are not found in primary dystonia.
abstract: OBJECTIVE
  To determine the contribution of TUBB4A, recently associated with DYT4 dystonia in a pedigree with "whispering dysphonia" from Norfolk, United Kingdom, to the etiopathogenesis of primary dystonia.
  
  
  METHODS
  High-resolution melting and Sanger sequencing were used to inspect the entire coding region of TUBB4A in 575 subjects with primary laryngeal, segmental, or generalized dystonia.
  
  
  RESULTS
  No pathogenic variants, including the exon 1 variant (c.4C>G) identified in the DYT4 whispering dysphonia kindred, were found in this study.
  
  
  CONCLUSIONS
  The c.4C>G DYT4 mutation appears to be private, and clinical testing for TUBB4A mutations is not justified in spasmodic dysphonia or other forms of primary dystonia. Moreover, given its allelic association with leukoencephalopathy hypomyelination with atrophy of basal ganglia and cerebellum and protean clinical manifestations (chorea, ataxia, dysarthria, intellectual disability, dysmorphic facial features, and psychiatric disorders), DYT4 should not be categorized as a primary dystonia.
authors.affiliation: From the Departments of Neurology and Anatomy & Neurobiology (S.R.V., J.X., M.S.L.), University of Tennessee Health Science Center, Memphis, TN; Bastian Voice Institute (R.W.B.), Downers Grove, IL; Clinic for Child Neurology and Psychiatry (D.M.), Medical Faculty University of Belgrade, Serbia; and New York Center for Voice and Swallowing Disorders (A.B.), NY.
authors.forename: Satya R
authors.initials: SR
authors.lastname: Vemula
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xiao
authors.forename: Robert W
authors.initials: RW
authors.lastname: Bastian
authors.forename: Dragana
authors.initials: D
authors.lastname: Momčilović
authors.forename: Andrew
authors.initials: A
authors.lastname: Blitzer
authors.forename: Mark S
authors.initials: MS
authors.lastname: LeDoux
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D020821:Dystonic Disorders / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D056784:Leukoencephalopathies / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D014404:Tubulin / Q000235:genetics*; D006113:United Kingdom
chemical_list: C582076:TUBB4A protein, human; D014404:Tubulin