GNB1-Related Rod-Cone Dystrophy: A Case Report

Abstract

Introduction: The GNB1 (guanine nucleotide-binding protein, β1) gene encodes for the ubiquitous β1 subunit of heterotrimeric G proteins, which are associated with G-protein-coupled receptors (GPCRs). GNB1 mutations cause a neurodevelopmental disorder characterized by a broad clinical spectrum. A novel variant has recently been confirmed in a case of rod-cone dystrophy.

Case presentation: We describe the second confirmed case of a classical rod-cone dystrophy associated with a mutation located in exon 6 of GNB1 [NM_002074.5:c.217G>C, p.(Ala73Pro)] in a 56-year-old patient also presenting mild intellectual disability, attention deficit/hyperactivity disorder, and truncal obesity.

Conclusion: This paper confirms the role of GNB1 in the pathogenesis of a classic rod-cone dystrophy and highlights the importance of including this gene in the genetic analysis panel for inherited retinal diseases.

Keywords: Case report; GNB1; Inherited retinal disease; Retinitis pigmentosa; Rod-cone dystrophy.

Fig. 1.

a, b Fundus photographs demonstrating bilateral reduced caliber of arterial vessels, bilateral “salt and pepper” retinopathy. c, d Fundus autofluorescence (AF) photographs characterized by a hypoautofluorescent ring encircling the normal central 10° surrounded by a hyperautofluorescent zone delimited by vascular arcades and confluent hypofluorescent spots outside the latter. e, f EDI SD-OCT confirmed left cystoid macular edema and loss of parafoveolar photoreceptors in both eyes. The thickness of the choroid is slightly greater in the eye with cystoid macular edema (left eye) than in the right eye but otherwise still within normal range upon age.

Fig. 2.

Characteristics of the GNB1 missense variant identified. a Family pedigree showing co-segregation of this variant in the family and respective electropherograms (b). c Location and number of ClinVar pathogenic or likely pathogenic (PLP) missense in proximity of alanine 73, as well as protein alignment of this region of GNB1 in selected non-vertebrates, showing in yellow the non-conserved amino acids among the species.