Tubulinopathies continued: refining the phenotypic spectrum associated with variants in TUBG1

Stefanie Brock, Katrien Stouffs, Emmanuel Scalais, Marc D’Hooghe, Kathelijn Keymolen, Renzo Guerrini, William B. Dobyns, Nataliya Di Donato, Anna C. Jansen

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1132-1142
Number of pages11
JournalEuropean Journal of Human Genetics
Issue number8
StatePublished - Aug 1 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018, The Author(s).


Dive into the research topics of 'Tubulinopathies continued: refining the phenotypic spectrum associated with variants in TUBG1'. Together they form a unique fingerprint.

Cite this