CRB2 – Retinitis Pigmentosa

Retinitis pigmentosa (RP) is genetically heterogeneous. A Chinese consanguineous family was found to harbor a homozygous CRB2 missense variant, c.3745C>G (p.Arg1249Gly), in two affected siblings, with full segregation of the mutation and clinical RP phenotype confirmed by ophthalmic evaluations (PMID:30593785). However, analysis of CRB2 in 85 RP and 79 Leber congenital amaurosis patients identified sequence variants but no second‐allele hits, excluding autosomal recessive CRB2 variants as common causes of RP or LCA (PMID:15851977).

Functional studies in retinal pigment epithelium (RPE) cells showed that p.Arg1249Gly reduces CRB2 mRNA and protein stability, interferes with wild-type CRB2 expression, induces epithelial–mesenchymal transition, impairs RPE phagocytosis, and triggers apoptosis (PMID:30593785). These data support a loss-of-function mechanism for CRB2 in non-syndromic, autosomal recessive RP. Further replication in unrelated cohorts is needed to substantiate CRB2 as an RP gene. Key take-home: CRB2 screening may be warranted in consanguineous RP cases negative for established genes.

References

• Experimental eye research • 2019 • CRB2 mutation causes autosomal recessive retinitis pigmentosa. PMID:30593785
• Molecular vision • 2005 • Characterization of the Crumbs homolog 2 (CRB2) gene and analysis of its role in retinitis pigmentosa and Leber congenital amaurosis. PMID:15851977

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