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Clinical and mutational signatures of CRB1-associated retinopathies: a multicentre study
Mo-Ying Wang1,2,3, Feng-Juan Gao1,2,3, Yu-Qiao Ju1,2,3
1Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.
Insights
CRB1-associated retinopathies present distinct clinical signs like geographic macular degeneration and retinal thinning. Identifying these signatures aids in diagnosing CRB1 mutations and developing future therapies for inherited retinal diseases.
Area of Science:
- Ophthalmology
- Genetics
- Retinal Diseases
Background:
- CRB1 mutations are a cause of inherited retinal diseases (IRDs).
- Understanding the clinical and genetic characteristics of CRB1-associated retinopathies is crucial for diagnosis and treatment.
- This study aimed to delineate the specific signatures associated with CRB1 mutations.
Purpose of the Study:
- To identify and characterize the clinical and mutational signatures in patients with CRB1-associated retinopathies.
- To compare these signatures with other forms of inherited retinal diseases.
- To establish genotype-phenotype correlations for CRB1 mutations.
Main Methods:
- A multicentre retrospective cohort study involving 40 patients with CRB1 mutations and 40 controls with other inherited retinal diseases.
- Detailed phenotyping and genotyping were performed.
- Genotype-phenotype correlations were analyzed.
Main Results:
- Common clinical signatures in CRB1 patients include yellowish geographic macular degeneration, retinal dots, hyperopia, abnormal retinal lamination, epiretinal membrane, and pigment deposits.
- These signatures were significantly more prevalent in CRB1 patients compared to other IRDs.
- Null mutations correlated with early-onset severe retinal dystrophy/Leber congenital amaurosis, while missense mutations were more common in retinitis pigmentosa and macular dystrophy.
Conclusions:
- Distinct clinical and mutational signatures for CRB1-associated retinopathies were identified.
- These findings provide a comprehensive update for diagnosing CRB1-related conditions.
- The study lays the groundwork for future therapeutic interventions targeting CRB1 mutations.
Background:
To delineate the clinical and mutational signatures of patients with CRB1-associated retinopathies.
Methods:
This multicentre retrospective cohort study involved 40 patients with CRB1 mutations and 40 age-matched and gender-matched inherited retinal diseases (IRDs). The detailed phenotyping and genotyping characteristics and genotype‒phenotype correlations of the patients were analysed.
Results:
The mean age of CRB1 cohort was 27.33±14.63 years. Results showed that yellowish geographic macular degeneration (66.67%), small white or yellow dots (65.6%), hyperopia (62.5%), abnormally laminated retina (61.61%), epiretinal membrane (60.6%) and nummular pigment deposits (50%) were the most common signatures in patients with CRB1 mutations. These clinical signatures were notably more prevalent among CRB1 patients than among individuals in other IRD groups (p<0.001). Early-onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA) patients are more likely to present these signatures than retinitis pigmentosa (RP) and macular dystrophy (MD) patients. Furthermore, a significant reduction in central foveal thickness coupled with pronounced thickening of the peripheral retina was observed more distinctly in patients with EOSRD/LCA (p<0.001). The choroidal thickness was not significantly altered compared to the normal controls, but was markedly reduced in the other IRD groups (p<0.001). 55 pathogenic variants were identified, 20 of which were novel. Null mutations were associated with EOSRD/LCA patients, and missense mutations were more prevalent in MD and RP patients.
Conclusions:
Key clinical and mutational signatures were demonstrated in this study, providing a comprehensive update on CRB1-associated retinopathies that will aid in diagnosis and lay the foundation for future therapeutic studies.
