Abstract
Brain malformations have heterogeneous genetic backgrounds. Tubulinopathies are a wide range of brain malformations caused by variants in tubulin and microtubules-associated genes. Recently biallelic variants in TTC5, also known as stress responsive activator of p300, have been reported in 11 patients from seven families with developmental delay, intellectual disability, and brain malformations. Here, we report compound heterozygous frameshift variants in TTC5 in a Japanese boy who showed severe psychomotor developmental delay and pseudobulbar palsy with growth failure. Brain magnetic resonance imaging showed a simplified gyral pattern and undetectable anterior limb of the internal capsule, suggesting tubulinopathies. Immunoblotting using lymphoblastoid cells derived from the patient showed undetectable TTC5 protein. Ttc5 silencing by RNA interference in Neuro2a cells reduced Tubulin β3 protein level and caused abnormal cell cycle. Our report suggests a possible link between TTC5-related brain malformation and tubulinopathies.
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Acknowledgements
We would like to thank the patient’s family for participating in this work. We also thank Kyoko Kitagawa, Masumi Tsujimura and Aya Kitamoto for their technical assistance. This work was supported by Grants-in-Aid for Scientific Research (B) (JP20H03641), and (C) (JP 20K08236) from the Japan Society for the Promotion of Science, and grant by the Takeda Science Foundation.
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Miyamoto, S., Kato, M., Sugiyama, K. et al. A boy with biallelic frameshift variants in TTC5 and brain malformation resembling tubulinopathies. J Hum Genet 66, 1189–1192 (2021). https://doi.org/10.1038/s10038-021-00953-7
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DOI: https://doi.org/10.1038/s10038-021-00953-7