RDH11 – Retinitis Pigmentosa

RDH11 has been implicated in retinitis pigmentosa based on case‐level data from two independent studies. In the first study, three siblings of Italian‐American descent presented with atypical retinitis pigmentosa marked by retinal pigment epithelial mottling and other systemic features. (PMID:24916380)

Under an autosomal recessive inheritance model, compound heterozygous mutations in RDH11 were identified in the affected children. Specifically, one allele harbored a nonsense mutation and the second allele carried a distinct stop mutation, consistent with a loss‐of‑function mechanism. (PMID:24916380)

A second study expanded the phenotypic spectrum by reporting a Chinese patient with retinitis pigmentosa accompanied by additional findings such as rod‐cone dystrophy and juvenile cataracts. Trio‐based exome sequencing revealed compound heterozygosity, including a splice‐site variant that led to exon skipping and a missense change. (PMID:34988992)

Segregation analysis in the familial case provided evidence for co‐segregation in affected siblings, reinforcing the role of RDH11 mutations in disease pathogenesis. The recurrence of the nonsense mutation c.322C>T (p.Arg108Ter) further supports a mutational hotspot contributing to the retinal phenotype. (PMID:24916380)

Functional assessments, including immunofluorescence studies, demonstrated aberrant RDH11 protein localization and abnormal splicing, bolstering the hypothesis of a loss‐of‑function mechanism in retinal degeneration. Although these studies are observational, they provide important experimental support for the association. (PMID:34988992)

In summary, the convergence of genetic and functional evidence from two independent families establishes a moderate clinical validity for the association between RDH11 and retinitis pigmentosa. Key take‑home: RDH11 mutations under autosomal recessive inheritance offer a diagnostic marker for retinitis pigmentosa and can inform both clinical management and future research.

References

• Human Molecular Genetics • 2014 • New syndrome with retinitis pigmentosa is caused by nonsense mutations in retinol dehydrogenase RDH11 PMID:24916380
• Clinical Genetics • 2022 • A new phenotype of syndromic retinitis pigmentosa with myopathy is caused by mutations in retinol dehydrogenase 11 PMID:34988992

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