Tubulinopathies continued: refining the phenotypic spectrum associated with variants in TUBG1.
Eur J Hum Genet
; 26(8): 1132-1142, 2018 08.
Article
em En
| MEDLINE
| ID: mdl-29706637
ABSTRACT
Tubulinopathies are a heterogeneous group of conditions with a wide spectrum of clinical severity resulting from variants in genes of the tubulin superfamily. Variants in TUBG1 have been described in three patients with posterior predominant pachygyria and microcephaly. We here report eight additional patients with four novel heterozygous variants in TUBG1 identified by next-generation sequencing (NGS) analysis. All had severe motor and cognitive impairment and all except one developed seizures in early life. The core imaging features included a pachygyric cortex with posterior to anterior gradient, enlarged lateral ventricles most pronounced over the posterior horns, and variable degrees of reduced white matter volume. Basal ganglia, corpus callosum, brainstem, and cerebellum were often normal, in contrast to patients with variants in other tubulin genes where these structures are frequently malformed. The imaging phenotype associated with variants in TUBG1 is therefore more in line with the phenotype resulting from variants in LIS1 (a.k.a. PAFAH1B1). This difference may, at least in part, be explained by gamma-tubulin's physiological function in microtubule nucleation, which differs from that of alpha and beta-tubulin.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fenótipo
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Tubulina (Proteína)
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Mutação de Sentido Incorreto
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Lisencefalia
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Disfunção Cognitiva
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Microcefalia
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Child
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article