File(s) not publicly available
Identification and characterisation of a novel constitutional PIK3CA mutation in a child lacking the typical segmental overgrowth of "PIK3CA-Related Overgrowth Spectrum" (PROS)
journal contributionposted on 2023-06-08, 23:37 authored by Nataliya Di Donato, Andreas Rump, Ghayda M Mirzaa, Diana AlcantaraDiana Alcantara, Antony OliverAntony Oliver, Evelin Schrock, William B Dobyns, Mark O'DriscollMark O'Driscoll
Activating somatic PIK3CA mutations underlie a growing heterogeneous spectrum of segmental overgrowth disorders. We report the identification and evaluation of a novel de novo constitutional PIK3CA mutation (NM_006218.2:c.335T>A, p.Ile112Asn) in a child with congenital megalencephaly and macrosomia. Functional characterization of patient cells using a variety of endpoints demonstrates increased Phosphatidylinositol-3-kinase (PI3K) activity. The mutation lies in a linker region adjacent to the p85 (PIK3R2) binding domain of the p110a (PIK3CA) catalytic subunit of PI3K. We show that altered stoichiometry within the p85-p110 complex likely underlies the hyperactive PI3K-AKT-mTOR signaling in this instance. Our findings expand upon the recently proposed "PIK3CA-Related Overgrowth Spectrum" (PROS) associated with PIKC3A-mutations and PI3K hyper-activation, adding constitutional PIK3CA mutations as an underlying cause of megalencephaly and macrosomia in newborns. This article is protected by copyright. All rights reserved.
PublisherJohn Wiley & Sons
Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available