title: Mosaic dominant TUBB4A mutation in an inbred family with complicated hereditary spastic paraplegia.
abstract: BACKGROUND
  Mutations in TUBB4A have been associated with a spectrum of neurological conditions, ranging from the severe hypomyelination with atrophy of the basal ganglia and cerebellum syndrome to the clinically milder dystonia type 4. The presence of movement abnormalities was considered the common hallmark of these disorders.
  
  
  METHODS
  Clinical, neurological, and neuroimaging examinations, followed by whole exome sequencing and mutation analysis, were performed in a highly consanguineous pedigree with five affected children.
  
  
  RESULTS
  We identified a novel c.568C>T (p.H190Y) TUBB4A mutation that originated de novo in the asymptomatic mother. The affected subjects presented with an early-onset, slowly progressive spastic paraparesis of the lower limbs, ataxia, and brain hypomyelination, in the absence of dystonia or rigidity.
  
  
  CONCLUSIONS
  Our study adds complicated hereditary spastic paraplegia to the clinical spectrum of TUBB4A-associated neurological disorders. We establish genotype-phenotype correlations with mutations located in the same region in the tertiary structure of the protein.
authors.affiliation: Molecular Neurogenomics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.|Neurogenetics Laboratory, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.|Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, Sofia, Bulgaria.
authors.forename: Dahlia
authors.initials: D
authors.lastname: Kancheva
authors.affiliation: Department of Neurology, Medical University-Sofia, Sofia, Bulgaria.
authors.forename: Teodora
authors.initials: T
authors.lastname: Chamova
authors.affiliation: Department of Neurology, Medical University-Sofia, Sofia, Bulgaria.
authors.forename: Velina
authors.initials: V
authors.lastname: Guergueltcheva
authors.affiliation: Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, Sofia, Bulgaria.
authors.forename: Vanio
authors.initials: V
authors.lastname: Mitev
authors.affiliation: Department of Diagnostic Genomics, PathWest, QEII Medical Centre, Nedlands, WA, Australia.|Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, Perth, Australia.
authors.forename: Dimitar N
authors.initials: DN
authors.lastname: Azmanov
authors.affiliation: Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, Perth, Australia.
authors.forename: Luba
authors.initials: L
authors.lastname: Kalaydjieva
authors.affiliation: Department of Neurology, Medical University-Sofia, Sofia, Bulgaria.|Department of Cognitive Science and Psychology, New Bulgarian University, Sofia, Bulgaria.
authors.forename: Ivailo
authors.initials: I
authors.lastname: Tournev
authors.affiliation: Molecular Neurogenomics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.|Neurogenetics Laboratory, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.|Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, Sofia, Bulgaria.
authors.forename: Albena
authors.initials: A
authors.lastname: Jordanova
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001259:Ataxia / Q000235:genetics; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D007223:Infant; D035002:Lower Extremity / Q000503:physiopathology; D008297:Male; D009030:Mosaicism; D009154:Mutation; D009186:Myelin Sheath / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D035781:Siblings; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D014404:Tubulin / Q000235:genetics*
chemical_list: C582076:TUBB4A protein, human; D014404:Tubulin
keywords: H-ABC; TUBB4A; hereditary spastic paraplegia; mosaicism