SLC35A2 somatic variants in drug resistant epilepsy: FCD and MOGHE.
Neurobiol Dis
; 187: 106299, 2023 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-37739137
ABSTRACT
De novo somatic (post-zygotic) gene mutations affecting neuroglial progenitor cell types in embryonic cerebral cortex are increasingly identified in patients with drug resistant epilepsy (DRE) associated with malformations of cortical development, in particular, focal cortical dysplasias (FCD). Somatic variants in at least 16 genes have been linked to FCD type II, all encoding components of the mechanistic target of rapamycin (mTOR) pathway. FCD type II is characterized histopathologically by cytomegalic dysmorphic neurons and balloon cells. In contrast, the molecular pathogenesis of FCD I subtypes is less well understood, and histological features are characterized by alterations in columnar or laminar organization without cytomegalic dysmorphic neurons or balloon cells. In 2018, we reported somatic mutations in Solute Carrier Family 35 member A2 (SLC35A2) linked to DRE underlying FCD type I and subsequently to a new histopathological phenotype excess oligodendrocytes and heterotopic neurons in subcortical white matter known as MOGHE (mild malformation of cortical development with oligodendroglial hyperplasia). These discoveries opened the door to studies linking somatic mutations to FCD. In this review, we discuss the biology of SLC35A2 somatic mutations in epilepsy in FCD and MOGHE, and insights into SLC35A2 epilepsy pathogenesis, describing progress to date and critical areas for investigation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Epilepsia
/
Malformaciones del Desarrollo Cortical
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Malformaciones del Desarrollo Cortical de Grupo I
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Epilepsia Refractaria
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Displasia Cortical Focal
Límite:
Humans
Idioma:
En
Revista:
Neurobiol Dis
Asunto de la revista:
NEUROLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos