CLINICAL CASE REPORT Unique retinal signaling defect in GNB5-related disease Zhuo Shao . Anupreet Tumber . Jason Maynes . Erika Tavares . Peter Kannu . Elise Heon . Ajoy Vincent Received: 24 July 2019 / Accepted: 5 November 2019 Ó Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Objective To report a unique retinal signaling defect in GNB5-related disease. Methods A 3-year-old female child underwent detailed systemic and ophthalmological evaluation. The eye examination included fundus photography, spectral domain optical coherence tomography and an extended protocol full-field electroretinography (ERG) including the ISCEV recommended standard steps. The dark-adapted (DA) ERGs were performed to a series of white flashes (range 0.006–30.0 cd s m -2 ) and two red flashes. The DA ERGs to higher stimulus intensities (3.0, 10.0 and 30.0 cd s m -2 ) were tested using a range of inter- stimulus intervals (ISI) of up to 60 s. In addition to standard light-adapted (LA) ERGs, a short-duration (0.5 s) LA 3.0 30-Hz flicker ERG and a long-duration LA ON–OFF ERG were also performed. Genetic testing included microarray, mitochondrial genome testing and whole exome sequencing. Results The child was diagnosed to have status epilepticus and bradycardia at 6 months of age. Subsequently, she was diagnosed to have global developmental delay and hypotonia. On ophthalmo- logical evaluation, the child fixes and follows light. Fundus evaluation showed mild optic disk pallor; macular SD-OCT was normal. The dim flash DA ERGs (DA 0.006 and DA 0.01 cd s m -2 ) were non- detectable. DA red flash ERGs showed the presence of an x-wave (cone component) and no rod component. The DA 3.0, 10.0 and 30.0 ERGs showed electroneg- ative configuration regardless of the ISI; the averaged a-wave amplitude (4 flashes) was smaller at shorter ISI but became normal at a prolonged ISI (60 s). The LA 30-Hz flicker ERG was severely reduced but detectable for the initial 0.5 s; this became non- detectable after 5 s of averaging. The LA 3.0 2-Hz ERG showed markedly reduced a- and b-wave ampli- tudes and a reduced b:a ratio; the LA ON–OFF ERGs were non-detectable. WES identified a homozygous null mutation in G protein subunit beta 5 (GNB5; c.1032C [ A/p.Tyr344*). Conclusion This report identifies for the first time a unique retinopathy associated with biallelic mutations in GNB5. The observed phenotype is consistent with a Z. Shao Á P. Kannu Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Canada A. Tumber Á E. Heon Á A. Vincent (&) Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, University of Toronto, Toronto, Canada e-mail: ajoy.vincent@sickkids.ca J. Maynes Division of Molecular Medicine, The Hospital for Sick Children Faculty of Medicine, University of Toronto, Toronto, Canada E. Tavares Á P. Kannu Á E. Heon Á A. Vincent Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada 123 Doc Ophthalmol https://doi.org/10.1007/s10633-019-09735-1