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Título

A NOVEL MISSENSE VARIANT IN GRM6 LEADS TO AUTOSOMAL RECESSIVE SCHUBERT BORNSCHEIN CONGENITAL STATIONARY NIGHT BLINDNESS

Resumo

INTRODUCTION: Congenital Stationary Night Blindness (CSNB) is a heterogeneous group of rare genetic disorders manifesting with nyctalopia(1). Complete CSNB is characterized by a defect on ON bipolar cells, leading to a dysfunction in transmission through these cells which is evidenced by a lack of the b-wave on scotopic ERG (2,3). The disease is very rare, and sporadic cases have been reported in the world literature until now. PURPOSE: To present the clinical and molecular aspects of three cases and two families, the first complete CSNB Brazilian cases reported in the literature. METHODS: Retrospective review of the medical records of consented patients. All studies were performed for clinical and not research indications. Examination included central fundus photography, fundus autofluorescence (FAF), spectral-density optical coherence tomography (OCT), ERG in accordance with the International Society for Clinical Electrophysiology of Vision Standards. All patients were tested with a sponsored IRD NGS testing of 330 genes. RESULTS: Three patients (two female and one male) from two different families presented to the ophthalmologic evaluation with lifelong nyctalopia. No strabismus and no nystagmus were present. The visual acuity ranged from 20/20 to 20/50-1. Two patients presented myopic fundus changes; one had a normal fundus examination. All three patients presented normal FAF and normal OCT. The full-field ERG showed a reduced rod-specific b wave and an electronegative waveform in the dark-adapted bright-flash ERG. Photopic responses were within normal limits. The retinal gene analyses revealed a homozygous variant, namely GRM6: c.2003T>C (p.Leu668Pro), of autosomal recessive inheritance that is associated with the complete form of CSNB. CONCLUSION: A full-field electroretinogram is essential in the clinical diagnosis of CSNB. It should be indicated in patients with visual difficulties in the dark and in myopic patients who do not achieve normal visual acuity for their age. CSNB is a rare disease, but the series presented here, one case without myopia and with normal visual acuity, demonstrate how the diagnosis can go unnoticed in daily practice and suggest that CSNB may be an underdiagnosed condition. Our findings add a variant in GRM6 associated with autosomal recessive complete CSNB, the first series in Brazilian population.

Referências Bibliográficas

1. Zeitz C, Robson AG, Audo I. Congenital stationary night blindness: An analysis and update of genotype–phenotype correlations and pathogenic mechanisms. Prog Retin Eye Res. março de 2015;45:58–110.
2. Godara P, Cooper RF, Sergouniotis PI, Diederichs MA, Streb MR, Genead MA, et al. Assessing Retinal Structure in Complete Congenital Stationary Night Blindness and Oguchi Disease. Am J Ophthalmol. dezembro de 2012;154(6):987-1001.e1.
3. Tsang SH, Sharma T. Congenital Stationary Night Blindness. Em: Tsang SH, Sharma T, organizadores. Atlas of Inherited Retinal Diseases [Internet]. Cham: Springer International Publishing; 2018 [citado 19 de maio de 2023]. p. 61–4. (Advances in Experimental Medicine and Biology; vol. 1085).

Área

RETINA (Trabalhos)