Gradient of brain mosaic RHEB variants causes a continuum of cortical dysplasia.
Brain
/ pathology
Child
Child, Preschool
Epilepsy
/ etiology
Female
Hemimegalencephaly
/ diagnostic imaging
Humans
Male
Malformations of Cortical Development
/ diagnostic imaging
Mutation
Neurons
/ pathology
Ras Homolog Enriched in Brain Protein
/ genetics
TOR Serine-Threonine Kinases
/ genetics
Young Adult
Journal
Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
06
10
2020
revised:
06
12
2020
accepted:
07
12
2020
pubmed:
13
1
2021
medline:
3
11
2021
entrez:
12
1
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33434304
doi: 10.1002/acn3.51286
pmc: PMC7886042
doi:
Substances chimiques
RHEB protein, human
0
Ras Homolog Enriched in Brain Protein
0
MTOR protein, human
EC 2.7.1.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
485-490Informations de copyright
© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
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