Search results for "Gain of Function Mutation"
showing 3 items of 3 documents
Compassionate use of everolimus for refractory epilepsy in a patient with MTOR mosaic mutation
2020
Abstract The MTOR gene encodes the mechanistic target of rapamycin (mTOR), which is a core component of the PI3K-AKT-mTOR signaling pathway. Postzygotic MTOR variants result in various mosaic phenotypes, referred to in OMIM as Smith-Kinsgmore syndrome or focal cortical dysplasia. We report here the case of a patient, with an MTOR mosaic gain-of-function variant (p.Glu2419Lys) in the DNA of 41% skin cells, who received compassionate off-label treatment with everolimus for refractory epilepsy. This 12-year-old-girl presented with psychomotor regression, intractable seizures, hypopigmentation along Blaschko's lines (hypomelanosis of Ito), asymmetric regional body overgrowth, and ocular anomali…
Distal Arthrogryposis type 5 in an Italian family due to an autosomal dominant gain-of-function mutation of the PIEZO2 gene
2022
Abstract Background Arthrogryposis multiplex congenita (AMC) is a group of clinically and etiologically heterogeneous conditions, characterized by prenatal onset contractures affecting two or more joints. Its incidence is about 1 in 3000 live births. AMC may be distinguished into amyoplasia, distal and syndromic arthrogryposis. Distal arthrogryposis (DA) predominantly affects hands and feet. It is currently divided into more than ten subtypes (DA1, DA2A/B, DA3–10), based on clinical manifestations, gene mutations and inheritance pattern. Among them, only a few patients with DA5 have been reported. It is associated to a gain-of-function pathogenic variant of the PIEZO2 gene, encoding for an …
Impaired Binding to Junctophilin-2 and Nanostructural Alteration in CPVT Mutation
2021
Rationale: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare disease, manifested by syncope or sudden death in children or young adults under stress conditions. Mutations in the Ca 2+ release channel/RyR2 (type 2 ryanodine receptor) gene account for about 60% of the identified mutations. Recently, we found and described a mutation in RyR2 N-terminal domain, RyR2 R420Q . Objective: To determine the arrhythmogenic mechanisms of this mutation. Methods and Results: Ventricular tachycardias under stress conditions were observed in both patients with catecholaminergic polymorphic ventricular tachycardia and knock-in mice. During action potential recording (by patch-clamp in …