RLBP1 – Fundus Albipunctatus

Autosomal recessive biallelic variants in RLBP1, encoding cellular retinaldehyde‐binding protein (CRALBP), have been implicated in fundus albipunctatus with associated cone dystrophy. In a cohort of 13 patients affected by white-dot retinopathies, one individual presented with fundus albipunctatus and cone dystrophy harboring compound RLBP1 variants (e.g., c.893G>A (p.Gly298Asp)) ([PMID:22559933]). No additional unrelated fundus albipunctatus families with RLBP1 variants have been described, and segregation beyond the index case was not reported.

In vitro assays of CRALBP harboring p.Met225Lys and p.Arg233Trp demonstrate severely reduced or abolished 11-cis-retinoid binding and substrate carrier activity, confirming a loss-of-function mechanism ([PMID:12536144]). A zebrafish rlbp1a knockout recapitulates fundus white-dot lesions, subretinal lipid droplets, and cone photoreceptor dysfunction, mirroring human pathology and reinforcing pathogenicity ([PMID:34668483]). While functional concordance is robust, the paucity of clinical cases restricts the gene–disease association to a Limited level. RLBP1 genetic testing may aid diagnosis in suspected fundus albipunctatus cases, but further cohort studies are needed for definitive validation.

References

• Ophthalmology • 2012 • A homozygous frameshift mutation in LRAT causes retinitis punctata albescens. PMID:22559933
• The Journal of biological chemistry • 2003 • Disease-causing mutations in the cellular retinaldehyde binding protein tighten and abolish ligand interactions. PMID:12536144
• eLife • 2021 • Disturbed retinoid metabolism upon loss of rlbp1a impairs cone function and leads to subretinal lipid deposits and photoreceptor degeneration in the zebrafish retina. PMID:34668483

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