Clinical and Molecular Characterization of Achromatopsia Patients: A Longitudinal Study
Autor: | Paolo Melillo, Raffaella Brunetti-Pierri, Sandro Banfi, Valentina Di Iorio, Gennarfrancesco Iaccarino, Antonella De Benedictis, Francesca Simonelli, Marianthi Karali, Francesco Testa |
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Přispěvatelé: | Brunetti-Pierri, R., Karali, M., Melillo, P., Di Iorio, V., De Benedictis, A., Iaccarino, G., Testa, F., Banfi, S., Simonelli, F. |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male Longitudinal study Achromatopsia genetic structures DNA Mutational Analysis CNGB3 Color Vision Defects lcsh:Chemistry chemistry.chemical_compound 0302 clinical medicine GNAT2 Longitudinal Studies lcsh:QH301-705.5 Spectroscopy Genetic disorder CNGA3 cone photoreceptors General Medicine Prognosis Heterotrimeric GTP-Binding Proteins Computer Science Applications Pedigree Phenotype Child Preschool Cohort Female achromatopsia Erg Tomography Optical Coherence Adult medicine.medical_specialty Adolescent Cyclic Nucleotide-Gated Cation Channels Catalysis Article Inorganic Chemistry 03 medical and health sciences Young Adult Ophthalmology medicine Humans Physical and Theoretical Chemistry Eye Proteins Molecular Biology Retrospective Studies Cyclic Nucleotide Phosphodiesterases Type 6 business.industry Organic Chemistry Retinal Cone photoreceptor medicine.disease eye diseases 030104 developmental biology chemistry lcsh:Biology (General) lcsh:QD1-999 Italian cohort Mutation 030221 ophthalmology & optometry sense organs business Progressive disease Biomarkers |
Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 1681, p 1681 (2021) Volume 22 Issue 4 |
ISSN: | 1422-0067 |
Popis: | Achromatopsia (ACHM) is a rare genetic disorder of infantile onset affecting cone photoreceptors. To determine the extent of progressive retinal changes in achromatopsia, we performed a detailed longitudinal phenotyping and genetic characterization of an Italian cohort comprising 21 ACHM patients (17 unrelated families). Molecular genetic testing identified biallelic pathogenic mutations in known ACHM genes, including four novel variants. At baseline, the patients presented a reduced best corrected visual acuity (BCVA), reduced macular sensitivity (MS), normal dark-adapted electroretinogram (ERG) responses and undetectable or severely reduced light-adapted ERG. The longitudinal analysis of 16 patients (mean follow-up: 5.4 ± 1.0 years) showed a significant decline of BCVA (0.012 logMAR/year) and MS (−0.16 dB/year). Light-adapted and flicker ERG responses decreased below noise level in three and two patients, respectively. Only two patients (12.5%) progressed to a worst OCT grading during the follow-up. Our findings corroborate the notion that ACHM is a progressive disease in terms of BCVA, MS and ERG responses, and affects slowly the structural integrity of the retina. These observations can serve towards the development of guidelines for patient selection and intervention timing in forthcoming gene replacement therapies. |
Databáze: | OpenAIRE |
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