Spectrum of Disease Severity in Nonsyndromic Patients With Mutations in the CEP290 Gene: A Multicentric Longitudinal Study
| Autor: | Sandro Banfi, Raffaella Brunetti-Pierri, Vittoria Murro, Enza Maria Valente, Paolo Melillo, Valentina Di Iorio, Francesco Testa, Andrea Sodi, Francesca Simonelli, Marianthi Karali, Sabrina Signorini |
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| Přispěvatelé: | Testa, F., Sodi, A., Signorini, S., Di Iorio, V., Murro, V., Brunetti-Pierri, R., Valente, E. M., Karali, M., Melillo, P., Banfi, S., Simonelli, F. |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male Longitudinal study Time Factors genetic structures DNA Mutational Analysis Cell Cycle Proteins Nystagmus Leber congenital amaurosi Severity of Illness Index chemistry.chemical_compound 0302 clinical medicine Child medicine.diagnostic_test Pedigree Phenotype Child Preschool Female medicine.symptom Erg Retinal Dystrophies Tomography Optical Coherence Cohort study medicine.medical_specialty Adolescent CEP290 gene Leber congenital amaurosis Retina 03 medical and health sciences Young Adult Antigens Neoplasm Ophthalmology retinitis pigmentosa Severity of illness medicine Electroretinography Humans business.industry Retinal DNA eye diseases Cytoskeletal Proteins 030104 developmental biology chemistry Mutation 030221 ophthalmology & optometry business Follow-Up Studies early onset severe retinal dystrophy |
| Zdroj: | Investigative Ophthalmology & Visual Science |
| ISSN: | 1552-5783 |
| Popis: | PURPOSE. The purpose of this study was to perform a detailed longitudinal phenotyping and genetic characterization of 32 Italian patients with a nonsyndromic retinal dystrophy and mutations in the CEP290 gene. METHODS. We reviewed the clinical history and examinations of 32 patients with a nonsyndromic retinal dystrophy due to mutations in the CEP290 gene, followed up (mean followup: 5.9 years) at 3 Italian centers. The clinical examinations included: best corrected visual acuity (BCVA), optical coherence tomography (OCT), and full-field electroretinogram (ERG). RESULTS. Patients (mean age = 19.0 ± 3.4 years) had a mean BCVA of 1.73 ± 0.20 logMAR. Longitudinal analysis of BCVA showed a nonsignificant decline. Central retinal thickness (CRT) declined significantly with age at an exponential rate of 1.0%/year (P = 0.001). At disease onset, most patients (19/32; 49.4%) had nystagmus. The absence of nystagmus was significantly associated with better BCVA and more preserved CRT (P < 0.05). ERG showed undetectable responses in most patients (64.0%), whereas reduced scotopic and photopic responses were observed in four patients (16.0%) who had no nystagmus. We identified 35 different variants, among which 12 were novel. Our genotype-phenotype correlation analysis shows a significantly worse BCVA in patients harboring a loss-of-function mutation and the deep-intronic variant c.2991+1655A>G. CONCLUSIONS. Our study highlights a mild phenotype of the disease, characterized by absence of nystagmus, good visual acuity, considerably preserved retinal morphology, and recordable ERG, confirming the wide spectrum of CEP290-related retinal dystrophies. Finally, in our cohort, the deep intronic variant c.2991+1655A>G was associated with a more severe phenotype. |
| Databáze: | OpenAIRE |
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