Monoallelic CRMP1 gene variants cause neurodevelopmental disorder

Ethiraj Ravindran, Nobuto Arashiki, Lena-Luise Becker, Kohtaro Takizawa, Jonathan Lévy, Thomas Rambaud, Konstantin L Makridis, Yoshio Goshima, Na Li, Maaike Vreeburg, Bénédicte Demeer, Achim Dickmanns, Alexander P A Stegmann, Hao Hu, Fumio Nakamura*, Angela M Kaindl

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Collapsin response mediator proteins (CRMPs) are key for brain development and function. Here, we link CRMP1 to a neurodevelopmental disorder. We report heterozygous de novo variants in the CRMP1 gene in three unrelated individuals with muscular hypotonia, intellectual disability and/or autism spectrum disorder. Based on in silico analysis these variants are predicted to affect the CRMP1 structure. We further analyzed the effect of the variants on the protein structure/levels and cellular processes. We showed that the human CRMP1 variants impact the oligomerization of CRMP1 proteins. Moreover, overexpression of the CRMP1 variants affect neurite outgrowth of murine cortical neurons. While altered CRMP1 levels have been reported in psychiatric diseases, genetic variants in CRMP1 gene have never been linked to human disease. We report for the first-time variants in the CRMP1 gene and emphasize its key role in brain development and function by linking directly to a human neurodevelopmental disease.

Original languageEnglish
Article numbere80793
Publication statusPublished - 13 Dec 2022


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