Abstract
Noncentrosomal microtubules are essential cytoskeletal filaments that are important for neurite formation, axonal transport, and neuronal migration. They require stabilization by microtubule minus-end-targeting proteins including the CLASP family of molecules. To date, no human monogenic disorder has been associated with the CLASP1 gene. In this study, we aimed to delineate the clinical and neuroradiologic phenotype associated with biallelic CLASP1 variants. We analyzed clinical characteristics, MRI data, and genotypes of a cohort of 3 patients with homozygous variants in CLASP1. Homozygous CLASP1 variant is associated with primary microcephaly, severe neurodevelopmental delay, and early-onset refractory epilepsy. The neuroradiologic phenotype comprises a highly recognizable combination of classic lissencephaly, with the posterior gradient more severe than the anterior gradient, a thin/hypoplastic splenium of the corpus callosum, mild enlargement of the lateral ventricles primarily posteriorly with a squared pattern, and pontine hypoplasia. This study underscores the role of CLASP1 in brain development and suggests that the identified variant disrupts CLASP1 interaction with the microtubule cytoskeleton, contributing to lissencephaly pathogenesis.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
