case_images: PMC10948171_01
case_images: PMC10948171_02
case_images: 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.
case_images: cop-2024-0015-0001-537997_F01.jpg
case_images: PMC10948171_02_cop-2024-0015-0001-537997_F01.jpg
case_images: F1
case_images: Slit-lamp examination revealed bilateral posterior cortical cataract, the ocular fundus characterized by bilateral reduced caliber of arterial vessels, bilateral "salt and pepper" retinopathy, and decreased foveolar reflex in the left eye caused by cystoid macular edema (shown in Fig. 1a, b). 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 (shown in Fig. 1e, f). Macular fundus autofluorescence was normal in the central 10  but was encircled by a hypoautofluorescent ring surrounded by a hyperautofluorescent zone delimited by vascular arcades; outside the latter, the retina was characterized by confluent hypofluorescent spots (shown in Fig. 1c, d).
case_images: 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.
case_images: cop-2024-0015-0001-537997_F02.jpg
case_images: PMC10948171_02_cop-2024-0015-0001-537997_F02.jpg
case_images: F2
case_images: Co-segregation analysis in the family revealed that the variant was absent from all available unaffected family members of the proband (shown in Fig. 2a, b), suggesting potential de novo inheritance, as it was the case for the two GNB1-associated ocular cases reported previously. The variant was classified as likely pathogenic using the ACMG classification for the neurological phenotype, according to criteria PM1, PM2, PM5, PP2, and PP3, the PM1 criterion being applicable since the variant lies within a mutational hotspot (shown in Fig. 2c). The variant also fulfilled the PM5 criterion since ClinVar included two entries for likely pathogenic variants affecting the same amino acid (Fig. 2c).