Gradient of brain mosaic RHEB variants causes a continuum of cortical dysplasia

Focal cortical dysplasia (FCD) and hemimegalencephaly (HME) are related malformations with shared etiologies. We report three patients with a spectrum of cortical malformations associated with pathogenic brain‐specific somatic Ras homolog enriched in brain (RHEB) variants. The somatic variant load d...

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Detalles Bibliográficos
Autores principales: Lee, Wei Shern, Baldassari, Sara, Chipaux, Mathilde, Adle‐Biassette, Homa, Stephenson, Sarah E. M., Maixner, Wirginia, Harvey, A. Simon, Lockhart, Paul J., Baulac, Stéphanie, Leventer, Richard J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Brief Communications
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886042/
https://www.ncbi.nlm.nih.gov/pubmed/33434304
http://dx.doi.org/10.1002/acn3.51286
Descripción
Sumario:Focal cortical dysplasia (FCD) and hemimegalencephaly (HME) are related malformations with shared etiologies. We report three patients with a spectrum of cortical malformations associated with pathogenic brain‐specific somatic Ras homolog enriched in brain (RHEB) variants. The somatic variant load directly correlated with the size of the malformation, with upregulated mTOR activity confirmed in dysplastic tissues. Laser capture microdissection showed enrichment of RHEB variants in dysmorphic neurons and balloon cells. Our findings support the role of RHEB in a spectrum of cortical malformations confirming that FCD and HME represent a disease continuum, with the extent of dysplastic brain directly correlated with the somatic variant load.

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