Dahlia Kancheva1,2,3, Teodora Chamova4, Velina Guergueltcheva4, Vanio Mitev3, Dimitar N Azmanov5,6, Luba Kalaydjieva6, Ivailo Tournev4,7, Albena Jordanova1,2,3. 1. Molecular Neurogenomics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium. 2. Neurogenetics Laboratory, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium. 3. Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, Sofia, Bulgaria. 4. Department of Neurology, Medical University-Sofia, Sofia, Bulgaria. 5. Department of Diagnostic Genomics, PathWest, QEII Medical Centre, Nedlands, WA, Australia. 6. Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, Perth, Australia. 7. Department of Cognitive Science and Psychology, New Bulgarian University, Sofia, Bulgaria.
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.
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: Paulo Victor Sgobbi de Souza; Wladimir Bocca Vieira de Rezende Pinto; Gabriel Novaes de Rezende Batistella; Thiago Bortholin; Acary Souza Bulle Oliveira Journal: Cerebellum Date: 2017-04 Impact factor: 3.847
Authors: Julien F Bally; Drew S Kern; Conor Fearon; Sarah Camargos; Francisco Pereira da Silva-Junior; Egberto Reis Barbosa; Laurie J Ozelius; Patricia de Carvalho Aguiar; Anthony E Lang Journal: Mov Disord Clin Pract Date: 2022-04-28