Title
Mosaic dominant TUBB4A mutation in an inbred family with complicated hereditary spastic paraplegia Mosaic dominant TUBB4A mutation in an inbred family with complicated hereditary spastic paraplegia
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
New York ,
Subject
Biology
Human medicine
Source (journal)
Movement disorders: video, videotape supplements. - New York
Volume/pages
30(2015) :6 , p. 854-858
ISSN
0885-3185
ISI
000354731500019
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
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 genotypephenotype correlations with mutations located in the same region in the tertiary structure of the protein.
E-info
https://repository.uantwerpen.be/docman/iruaauth/3a2ece/20d58996b1c.pdf
Full text (open access)
https://repository.uantwerpen.be/docman/irua/985273/9845.pdf
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