CHM/REP1 Transcript Expression and Loss of Visual Function in Patients Affected by Choroideremia.
Di Iorio Valentina, Esposito Gabriella, De Falco Francesca, Boccia Rosa, Fioretti Tiziana, Colucci Raffaella, De Rosa Giuseppe, Melillo Paolo, Salvatore Francesco, Simonelli Francesca
AI Summary
This study found choroideremia progresses slowly, but CHM/REP1 gene mutations causing absent mRNA lead to earlier, more severe vision and field loss, guiding prognosis and potential gene therapy.
Abstract
Purpose
To evaluate the disease progression in patients with clinical and genetic diagnoses of choroideremia during a long-term follow-up and to investigate the relationship between pathogenic variants in the CHM/REP1 gene and disease phenotypes.
Methods
We performed a retrospective longitudinal study on 51 affected men by reviewing medical charts at baseline and follow-up visits to extract the following ocular findings: best-corrected visual acuity, Goldmann visual field, optical coherence tomography, microperimetry. Data obtained from the analysis of DNA and mRNA were reevaluated for genetic classification of patients.
Results
The longitudinal analysis showed a significant (P < 0.001) worsening of best-corrected visual acuity with a mean rate of 0.011 logMar per year before 50 years and 0.025 logMar per year after 50 years. Similarly, V4e Goldmann visual field area significantly (P ≤ 0.01) decreased at a mean rate of 2.7% per year before 40 years and 5.7% after 40 years. Moreover, we observed a significant (P < 0.05) decrease of macular sensitivity with a mean rate of 5.0% per year and a decrease of mean macular thickness with a mean rate of 0.8% per year. We classified our patients into two groups according to the expression of the CHM/REP1 gene transcript and observed that mutations leading to mRNA absence are associated with an earlier best-corrected visual acuity and Goldmann visual field loss.
Conclusions
Our analysis of morphological and functional parameters in choroideremia patients showed a slow disease progression, particularly in the first decades of life. Overall, reevaluation of clinical and molecular data suggests exploring the genotype-phenotype relationship based on CHM/REP1 transcript expression.
MeSH Terms
Shields Classification
Key Concepts5
In patients with clinical and genetic diagnoses of choroideremia, best-corrected visual acuity worsened significantly (P < 0.001) at a mean rate of 0.011 logMar per year before 50 years of age and 0.025 logMar per year after 50 years of age.
In patients with clinical and genetic diagnoses of choroideremia, V4e Goldmann visual field area significantly (P ≤ 0.01) decreased at a mean rate of 2.7% per year before 40 years of age and 5.7% per year after 40 years of age.
In patients with clinical and genetic diagnoses of choroideremia, macular sensitivity significantly (P < 0.05) decreased at a mean rate of 5.0% per year.
In patients with clinical and genetic diagnoses of choroideremia, mean macular thickness significantly decreased at a mean rate of 0.8% per year.
In patients with clinical and genetic diagnoses of choroideremia, mutations leading to mRNA absence of the CHM/REP1 gene transcript are associated with an earlier best-corrected visual acuity and Goldmann visual field loss.
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