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Three novel gene variants (REEP6) found within a population of autosomal recessive retinitis pigmentosa (arRP) patients

Researchers, at the Henan Clinical Research Centre for Ophthalmic Diseases, Zhengzhou University, have reported a recent study identifying novel gene variants of the “REEP6” gene, encoding a protein for the development of photoreceptors leading to arRP (autosomal recessive retinitis pigmentosa).  The relevant protein, “receptor expressions-enhancing protein 6”, is understood to be involved in the transport of receptors from the endoplasmic reticulum to the cell surface. The REEP6 gene is required for the proper development of retinal rods and photoreceptors, and the gene is located on chromosome 19p13.3, associated with retinitis pigmentosa 77.  The novel findings of three variants in the REEP6 gene – a missense, frameshift and splicing variant – are now to be reported as “likely pathogenic” by the American College of Medical Genetics and Genomics (ACMG).


The research study used targeted next-generation sequencing (NGS), including both computational assessment and animal models, for the assessment of arRP subjects. According to the researchers, multiple lines of computational predictions, combined with in vitro lab work, were applied to assess the pathogenicity of the variants. Three novel variants found in the REEP6 gene included one missense variant (c.268G>C), one frameshift variant, (c.468delC), and one splicing variant (c.598+1G>C).  In addition to the NGS data, REEP6 variant proteins (c.268G>C and c.468delC) showed that in cultured cells these mutations destabilized the REEP6 protein and induced intracellular inclusions. Consequently, the data suggested that REEP6 c.268G>C may be a recurrent causative variant in Chinese autosomal recessive retinitis pigmentosa patients.


While eighty-nine (89) RP related genes have been identified to date (since Feb. 18th, 2021), ten causative REEP6 variants leading to RP have now been collated.  Accordingly, the ten causative variants in REEP6, associated with autosomal recessive retinitis pigmentosa, include five missense variants, two frameshift deletions, one duplication, one splicing variant, and one genomic rearrangement.   In terms of clinical evaluation, the researchers also showed that nyctalopia and gradually constricted visual fields were initial symptoms found in this cohort of adRP patients, followed by reduced visual acuity in all affected individuals in the ten families. In addition, fundus photography showed narrowed retinal vessels and bone-spicule deposits.  Finally, the report may now assist identifying several pedigrees within other populations.