Novel mutation in gene causing autosomal recessive progressive rod-cone dystrophy.

BACKGROUND

Recent advances in genetic sequencing techniques have improved the overall diagnostic yield for finding genetic causes for inherited retinal dystrophies (IRD). Rod-cone dystrophy is the most common IRD and is characterized by the primary involvement of the rod photoreceptors. Over 80 causal genes have been identified so far giving clinicians insight into the pathogenesis. encodes a sodium bicarbonate cotransporter responsible acid disposal which, within the retina, is prevalent in the photoreceptor synaptic terminals. Thus far, there have been no published reports of variants in this gene known to cause rod-cone dystrophy.

MATERIAL AND METHODS

Case report of a rod-cone dystrophy patient with a novel mutation in , whole exome sequencing with CLIA-certified NGS and Sanger confirmation, and, review of a knockout mouse model phenotype.

RESULTS

A 66-year-old male presented with slowly progressing night blindness, constricted visual field and relatively stable visual acuity. Fundus examination showed diffuse intraretinal pigment in the mid- and peripheral retina, diffuse retinal pigment epithelial atrophy, and intact macula in both eyes. There has been mild macular edema in both eyes which remained stable with the use of topical dorzolamide eyedrops. Whole exome sequencing found, and a subsequent vision panel confirmed, the pathogenic variant to be a homozygous frameshift mutation in which results in termination of the protein.

CONCLUSIONS

We report a case of progressive rod-cone dystrophy caused by a novel mutation in , a gene coding the sodium bicarbonate cotransporter NBC3, underscoring the importance of ion homeostasis for photoreceptor function and maintenance.