Identification of autosomal recessive novel genes and retinal phenotypes in members of the solute carrier (SLC) superfamily

Abstract

This study aimed to investigate the clinical and genetic aspects of solute carrier (SLC) genes in inherited retinal diseases (IRDs). Exome sequencing data were filtered to identify pathogenic variants in SLC genes. Analysis of transcript and protein expression was performed on fibroblast cell lines and retinal sections. Comprehensive analysis of 433 SLC genes in 913 exome sequencing IRD samples revealed homozygous pathogenic variants in 6 SLC genes, including 2 candidate novel genes, which were 2 variants in SLC66A1, causing autosomal recessive retinitis pigmentosa (ARRP), and a variant in SLC39A12, causing autosomal recessive mild widespread retinal degeneration with marked macular involvement. In addition, we present 4 families with ARRP and homozygous null variants in SLC37A3 that were previously suggested to cause retinitis pigmentosa, 2 of which cause exon skipping. The recently reported SLC4A7- c.2007dup variant was found in 2 patients with ARRP resulting in the absence of protein. Finally, variants in SLC24A1 were found in 4 individuals with either ARRP or congenital stationary night blindness. We report on SLC66A1 and SLC39A12 as candidate novel IRD genes, establish SLC37A3 pathogenicity, and provide further evidence of SLC4A7 as IRD genes. We extend the phenotypic spectrum of SLC24A1 and suggest that its ARRP phenotype may be more common than previously reported.