Fiche publication
Date publication
décembre 2024
Journal
European journal of human genetics : EJHG
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAHRAM Siamak
,
Dr CARAPITO Raphaël
Tous les auteurs :
Carapito R, Molitor A, Pavinato L, Skeyni A, Lambert M, Pichot A, Jiang J, Spinnhirny P, Zimmermann L, Boucher P, Chung CWT, Elserafy N, Blair EM, Li D, Elisabeth B, Kotzaeridou U, Karch S, Wagner M, Lunsing RJ, Pfundt R, Boycott KM, Bruel AL, Mau-Them FT, Moutton S, Conti V, Mei D, Cetica V, Guerrini R, Brunet T, Rump P, Mussa A, Brusco A, Lemire G, de Vries BBA, Miao Z, Isidor B, Bahram S
Lien Pubmed
Résumé
RICTOR is a key component of the mTORC2 signaling complex which is involved in the regulation of cell growth, proliferation and survival. RICTOR is highly expressed in neurons and is necessary for brain development. Here, we report eight unrelated patients presenting with intellectual disability and/or development delay and carrying variants in the RICTOR gene. The phenotypic presentation is diverse with associated features including growth failure, feeding difficulties, abnormal behavior, seizure, hypertonia, brain anomalies and various other congenital organ and skeletal malformations. All patients carried de novo or heterozygous variants inherited from one affected parent, including three missense variants, four loss-of-function variants and one 3 kb deletion encompassing RICTOR. The mTORC2 pathway was hyperactivated in a patient's fibroblasts carrying a missense variant, while the expression of RICTOR remained unchanged, indicating a gain-of-function mechanism. RNA sequencing on RICTOR knock-out mouse embryonic fibroblasts confirmed the potential role of RICTOR in neuronal cell development.
Référence
Eur J Hum Genet. 2024 12 30;:
