Mosaic dominant TUBB4A mutation in an inbred family with complicated hereditary spastic paraplegia.
Mov Disord
; 30(6): 854-8, 2015 May.
Article
em En
| MEDLINE
| ID: mdl-25772097
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.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Tubulina (Proteína)
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Paraplegia Espástica Hereditária
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Genes Dominantes
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Mosaicismo
Limite:
Adolescent
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Mov Disord
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Bélgica