Autosomal recessive variants in <i>TUBGCP2</i> alter the γ-tubulin ring complex leading to neurodevelopmental disease.

ABSTRACT: Microtubules help building the cytoskeleton of neurons and other cells. Several components of the gamma-tubulin (γ-tubulin) complex have been previously reported in human neurodevelopmental diseases. We describe two siblings from a consanguineous Turkish family with dysmorphic features, developmental delay, brain malformation, and epilepsy carrying a homozygous mutation (p.Glu311Lys) in TUBGCP2 encoding the γ-tubulin complex 2 (GCP2) protein. This variant is predicted to disrupt the electrostatic interaction of GCP2 with GCP3. In primary fibroblasts carrying the variant, we observed a faint delocalization of γ-tubulin during the cell cycle but normal GCP2 protein levels. Through mass spectrometry, we observed dysregulation of multiple proteins involved in the assembly and organizati

SUBMITTER: Gungor S 

PROVIDER: S-EPMC7797523 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature