University of Cambridge > > Babraham Seminar > RAC1 mutations in human neurodevelopmental disorders

RAC1 mutations in human neurodevelopmental disorders

Add to your list(s) Download to your calendar using vCal

  • UserDr Siddharth Banka & Dr Thomas Millard; University of Manchester
  • ClockMonday 20 July 2020, 12:00-13:00
  • HouseZoom Seminar.

If you have a question about this talk, please contact Bobbie Claxton.

This seminar will be online via zoom

RAC1 is a highly conserved Rho GTPase under strict mutational constraint. We describe patients with novel human disorder caused by germline de novo missense RAC1 mutations resulting in varying degrees of developmental delay, brain malformations, and additional phenotypes (1). Collectively, we observed an extraordinary spread of ∼10 SD of head circumferences orchestrated by distinct mutations in the same gene. In silico modelling, mouse fibroblasts spreading assays, and in vivo over-expression assays using zebrafish as a surrogate model demonstrated that the some RAC1 variants function as dominant-negative alleles and result in microcephaly, reduced neuronal proliferation, and cerebellar abnormalities in vivo. Conversely, some variants are constitutively active or their effects are context dependent. Currently we are working to expand the known spectrum of germline RAC1 mutations and improve the understanding of the mechanism of the disease. More recently, other Rho GTPases and their regulators have also been implicated in human neurodevelopmental disorders. Overall, these findings highlight the importance of Rho GTPases in normal human neurodevelopment and disease. 1. Reijnders et al Am J Hum Genet 2017 101 (3).

Join Zoom seminar:

Meeting ID: 981 6811 6369 Password: 803531

This talk is part of the Babraham Seminar series.

Tell a friend about this talk:

This talk is included in these lists:

Note that ex-directory lists are not shown.


© 2006-2024, University of Cambridge. Contact Us | Help and Documentation | Privacy and Publicity