Mosaic dominant TUBB4A mutation in an inbred family with complicated hereditary spastic paraplegia

D. Kancheva, T. Chamova, V. Guergueltcheva, V. Mitev, Dimitar Azmanov, Luba Kalaydjieva, I. Tournev, A. Jordanova

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

© 2015 International Parkinson and Movement Disorder Society © 2015 International Parkinson and Movement Disorder Society 30 6 May 2015 10.1002/mds.26196 Brief Report Brief Reports © 2015 International Parkinson and Movement Disorder Society. 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.
Original languageEnglish
Pages (from-to)854-858
JournalMovement Disorders
Volume30
Issue number6
DOIs
Publication statusPublished - 2015

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Hereditary Spastic Paraplegia
Mutation
Dystonia
Spastic Paraparesis
Exome
Neurologic Examination
Genetic Association Studies
Ataxia
Pedigree
Basal Ganglia
Nervous System Diseases
Tertiary Protein Structure
Neuroimaging
Cerebellum
Atrophy
Lower Extremity
Mothers
Brain

Cite this

Kancheva, D., Chamova, T., Guergueltcheva, V., Mitev, V., Azmanov, D., Kalaydjieva, L., ... Jordanova, A. (2015). Mosaic dominant TUBB4A mutation in an inbred family with complicated hereditary spastic paraplegia. Movement Disorders, 30(6), 854-858. https://doi.org/10.1002/mds.26196
Kancheva, D. ; Chamova, T. ; Guergueltcheva, V. ; Mitev, V. ; Azmanov, Dimitar ; Kalaydjieva, Luba ; Tournev, I. ; Jordanova, A. / Mosaic dominant TUBB4A mutation in an inbred family with complicated hereditary spastic paraplegia. In: Movement Disorders. 2015 ; Vol. 30, No. 6. pp. 854-858.
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Kancheva, D, Chamova, T, Guergueltcheva, V, Mitev, V, Azmanov, D, Kalaydjieva, L, Tournev, I & Jordanova, A 2015, 'Mosaic dominant TUBB4A mutation in an inbred family with complicated hereditary spastic paraplegia' Movement Disorders, vol. 30, no. 6, pp. 854-858. https://doi.org/10.1002/mds.26196

Mosaic dominant TUBB4A mutation in an inbred family with complicated hereditary spastic paraplegia. / Kancheva, D.; Chamova, T.; Guergueltcheva, V.; Mitev, V.; Azmanov, Dimitar; Kalaydjieva, Luba; Tournev, I.; Jordanova, A.

In: Movement Disorders, Vol. 30, No. 6, 2015, p. 854-858.

Research output: Contribution to journalArticle

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T1 - Mosaic dominant TUBB4A mutation in an inbred family with complicated hereditary spastic paraplegia

AU - Kancheva, D.

AU - Chamova, T.

AU - Guergueltcheva, V.

AU - Mitev, V.

AU - Azmanov, Dimitar

AU - Kalaydjieva, Luba

AU - Tournev, I.

AU - Jordanova, A.

PY - 2015

Y1 - 2015

N2 - © 2015 International Parkinson and Movement Disorder Society © 2015 International Parkinson and Movement Disorder Society 30 6 May 2015 10.1002/mds.26196 Brief Report Brief Reports © 2015 International Parkinson and Movement Disorder Society. 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.

AB - © 2015 International Parkinson and Movement Disorder Society © 2015 International Parkinson and Movement Disorder Society 30 6 May 2015 10.1002/mds.26196 Brief Report Brief Reports © 2015 International Parkinson and Movement Disorder Society. 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.

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