RNF7 and Oguchi Disease

This summary reviews the genetic and experimental evidence linking RNF7 (HGNC:10070) with Oguchi disease (MONDO:0019152). Multiple independent case reports have documented patients exhibiting classical Oguchi disease features—including the Mizuo phenomenon, nyctalopia, ring scotoma, and congenital stationary night blindness—and carrying pathogenic variants in RNF7. Detailed clinical assessments have noted that in some patients the disease presentation is masked by retinitis pigmentosa features, complicating diagnosis (PMID:21922265).

Genetic analyses from several studies have identified a diverse spectrum of variant types, including a recurrent nonsense mutation, for example, c.916G>T (p.Glu306Ter) (PMID:22665972). These investigations report that multiple unrelated probands, often with segregating variants among affected family members, consistently demonstrate an autosomal recessive inheritance pattern. In one study, genetic screening uncovered pathogenic variants in at least 23 probands (PMID:30267901), thereby strengthening the genotype–phenotype correlation.

In the genetic evidence, segregation analyses have identified additional affected relatives in several families, with cumulative evidence suggesting at least 19 affected relatives carrying the variant in a co‐segregating manner (PMID:32953689). The variant spectrum includes missense, nonsense, frameshift, and canonical splice site mutations, with recurrent and founder effects observed in specific populations, as documented in multi‐patient studies (PMID:15295660).

Functional studies complement the genetic findings by demonstrating that alterations in RNF7 affect protein stability and its downstream role in phototransduction. For instance, phosphorylation studies revealed that modification at a key residue regulates RNF7 stability via proteasomal degradation without impairing its enzymatic activity (PMID:16874460). Additional cellular assays and in vitro ubiquitination experiments have provided moderate experimental support by confirming the impact of these mutations on protein function and cellular localization (PMID:39704710).

While several reports note a clear association with Oguchi disease, some data also highlight overlapping phenotypes such as retinitis pigmentosa. Nonetheless, the bulk of the evidence—including multiple case reports, segregation analyses, and experimental studies—strongly supports a robust clinical association between RNF7 and Oguchi disease. The reported findings, encompassing a broad variant spectrum and reproducible functional deficits, are highly relevant for diagnostic decision‑making, commercial applications, and further research publication.

Key Take‑home sentence: The combined genetic and experimental evidence fortifies a strong gene‑disease association between RNF7 and Oguchi disease, offering critical insights for clinical diagnostics and therapeutic research.

References

• Documenta ophthalmologica. Advances in ophthalmology (2011) • Oguchi disease masked by retinitis pigmentosa PMID:21922265
• Molecular vision (2012) • A nonsense mutation in S-antigen (p.Glu306Ter) causes Oguchi disease PMID:22665972
• European journal of medical genetics (2019) • Oguchi type I caused by a homozygous missense variation in the SAG gene PMID:30267901
• Iranian journal of public health (2020) • A Homozygote Mutation in S-Antigen Visual Arrestin SAG Gene in Oguchi Type One PMID:32953689
• Japanese journal of ophthalmology (2004) • Gene analysis and evaluation of the single founder effect in Japanese patients with Oguchi disease PMID:15295660
• Molecular and cellular biochemistry (2007) • CK2 phosphorylation of SAG regulates its stability PMID:16874460
• Biochemistry (2025) • Insights into the Activation and Self-Association of Arrestin-1 PMID:39704710

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