Somatic mosaicism of the PI3K-AKT-MTOR pathway is associated with hemimegalencephaly in fetal brains.
AKT1
PIK3CA
hemimegalencephaly
heterotopia
polymicrogyria
Journal
Neuropathology : official journal of the Japanese Society of Neuropathology
ISSN: 1440-1789
Titre abrégé: Neuropathology
Pays: Australia
ID NLM: 9606526
Informations de publication
Date de publication:
Apr 2023
Apr 2023
Historique:
revised:
06
10
2022
received:
20
07
2022
accepted:
11
10
2022
medline:
4
4
2023
pubmed:
4
11
2022
entrez:
3
11
2022
Statut:
ppublish
Résumé
It is known that somatic activation of PI3K-AKT-MTOR signaling causes malformations of cortical development varying from hemimegalencephaly to focal cortical dysplasia. However, there have been few reports of fetal cases. Here we report two fetal cases of hemimegalencephaly, one associated with mosaic mutations in PIK3CA and another in AKT1. Both brains showed polymicrogyria, multiple subarachnoidal, subcortical, and subventricular heterotopia resulting from abnormal proliferation of neural stem/progenitor cells, cell differentiation, and migration of neuroblasts. Scattered cell nests immunoreactive for phosphorylated-S6 ribosomal protein (P-RPS6) (Ser240/244) were observed in the polymicrogyria-like cortical plate, intermediate zone, and arachnoid space, suggesting that the PI3K-AKT-MTOR pathway was actually activated in these cells. Pathological analyses could shed light on the mechanisms involved in disrupted brain development in the somatic mosaicism of the PI3K-AKT-MTOR pathway.
Substances chimiques
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
TOR Serine-Threonine Kinases
EC 2.7.11.1
MTOR protein, human
EC 2.7.1.1
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
190-196Subventions
Organisme : JSPS-KAKENHI, Grants-in-Aid for Scientific Research
ID : 21H02883
Informations de copyright
© 2022 Japanese Society of Neuropathology.
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