UNC119 and Cone‑rod Dystrophy

Recent multi‑patient genetic studies have identified ultra‑rare heterozygous variants in UNC119 (HGNC:12565) in individuals with cone‑rod dystrophy (MONDO:0015993). In one study screening 163 probands, mutations in UNC119 were observed in approximately 0.6% of cases (PMID:26992781), while a second study reported the heterozygous UNC119 variant c.259G>A (p.Asp87Asn) in 1 out of 130 unrelated probands (PMID:23563732).

The genetic evidence supporting the association is currently limited by the very low frequency of these variants and by the absence of detailed segregation data in affected families. No extended familial analyses or segregation studies were reported that could strengthen the genotype‑phenotype correlation.

Furthermore, while functional studies in other disease contexts have demonstrated that UNC119 plays important roles in protein trafficking and cellular signaling, there have been no direct functional or experimental assessments performed in retinal tissue or cellular models pertinent to cone‑rod dystrophy. Thus, the experimental support for a direct mechanistic role in retinal degeneration is lacking.

Integration of the available genetic and limited experimental data suggests that UNC119 is a potential, albeit rare, contributor to cone‑rod dystrophy. Additional studies incorporating robust segregation analysis and relevant functional assays in retinal models are needed before this association can be considered definitive.

Key take‑home: Despite the limited evidence, the detection of a recurrent heterozygous variant in UNC119 provides a clinical cue for further genetic testing and research in cone‑rod dystrophy, reinforcing its potential diagnostic utility.

References

• Experimental Eye Research • 2016 • Molecular genetics of cone‑rod dystrophy in Chinese patients: New data from 61 probands and mutation overview of 163 probands PMID:26992781

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