Mutations in the Crumbs homologue 1 (CRB1) gene have been reported in patients with a variety of autosomal recessive retinal dystrophies, including retinitis pigmentosa (RP) with preserved paraarteriolar retinal pigment epithelium (PPRPE), RP with Coats-like exudative vasculopathy, early onset RP without PPRPE, and Leber congenital amaurosis (LCA). We extended our investigations of CRB1 in these retinal dystrophies, and identified nine novel CRB1 sequence variants. In addition, we screened patients with "classic" RP and classic Coats disease (without RP), but no pathologic sequence variants were found in the CRB1 gene. In total, 71 different sequence variants have been identified on 184 CRB1 alleles of patients with retinal dystrophies, including amino acid substitutions, frameshift, nonsense, and splice site mutations, in-frame deletions, and large insertions. Recent studies in two animal models, mouse and Drosophila, and in vivo high-resolution microscopy in patients with LCA, have shed light on the role of CRB1 in the pathogenesis of retinal dystrophies and its function in the photoreceptors. In this article, we provide an overview of the currently known CRB1 sequence variants, predict their effect, and propose a genotype-phenotype correlation model for CRB1 mutations.

The reading performance of most patients with RP is only moderately impaired. It correlates with contrast sensitivity, visual acuity, and visual field. It should be assessed in all cases, as disability can ensue, even when visual acuity is preserved. In patients with RP with poor reading performance, there is little potential for high-magnification devices because visual field constriction affects the reading rate.

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