Title

Second patient with GNB2-related neurodevelopmental disease: Further evidence for a gene-disease association.

Document Type

Article

Publication Date

7-2021

Identifier

DOI: 10.1016/j.ejmg.2021.104243

Abstract

G-proteins are ubiquitously expressed heterotrimeric proteins consisting of α, β and γ subunits and mediate G-protein coupled receptor signalling cascades. The β subunit is encoded by one of five highly similar paralogs (GNB1-GNB5, accordingly). The developmental importance of G-proteins is highlighted by the clinical relevance of variants in genes such as GNB1, which cause severe neurodevelopmental disease (NDD). Recently the candidacy of GNB2 was raised in association with NDD in an individual with a de novo variant affecting a codon conserved across paralogs and recurrently mutated in GNB1-related disease, c.229G>A p.(Gly77Arg), in association with global developmental delay, intellectual disability and dysmorphic features. Here, we report a patient with strikingly similar facial features and NDD in association with a de novo GNB2 variant affecting the same codon, c.229G>T p.(Gly77Trp). In addition, this individual has epilepsy and overgrowth. Our report is the second to implicate a de novo GNB2 variant with a severe yet variable NDD.

Journal Title

Eur J Med Genet

Volume

64

Issue

7

First Page

104243

Last Page

104243

Keywords

Exome; G-proteins; GNB2; Neurodevelopmental disease; Variant

Library Record

Share

COinS