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
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