Two New Cases Expand the Phenotypic Spectrum of TUBG1 Missense Variants

Abstract

The gamma-tubulin ring complex (γ-TuRC) plays a role in coordinating centrosome and spindle pole body formation during cell division. TUBG1 encodes a critical component of the γ-TuRC. Pathogenic TUBG1 variants can cause a range of alterations in cortical gyral patterning, microcephaly, and other neurological manifestations. We describe two missense variants in TUBG1 and their associated clinical phenotypes. One individual has microcephaly, epilepsy, and a simplified gyral pattern with a TUBG1 variant interpreted as pathogenic. The other individual has a likely pathogenic TUBG1 variant that explains the milder presentation of autism spectrum disorder, intellectual disability, later-onset well-controlled epilepsy, a normocephalic head size, and no detectable structural abnormalities on neuroimaging.

Keywords: TUBG1; epilepsy; intellectual disability; lissencephaly; microcephaly.