Dataset Information

Clinical and Molecular Characterization of Achromatopsia Patients: A Longitudinal Study.

ABSTRACT: 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.

SUBMITTER: Brunetti-Pierri R

PROVIDER: S-EPMC7914547 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Clinical and Molecular Characterization of Achromatopsia Patients: A Longitudinal Study.

Brunetti-Pierri Raffaella R Karali Marianthi M Melillo Paolo P Di Iorio Valentina V De Benedictis Antonella A Iaccarino Gennarfrancesco G Testa Francesco F Banfi Sandro S Simonelli Francesca F

International journal of molecular sciences 20210207 4

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 correc ...[more]

PMID: 33562422

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Project description:Objectives: To characterize the temporal characteristics of clinical variables with time lock to mortality and build a predictive model of mortality associated with COVID-19 using clinical variables. Design: Retrospective cohort study of the temporal characteristics of clinical variables with time lock to mortality. Setting: Stony Brook University Hospital (New York) and Tongji Hospital. Patients: Patients with confirmed positive for severe acute respiratory syndrome coronavirus-2 using polymerase chain reaction testing. Patients from the Stony Brook University Hospital data were used for training (80%, N = 1,002) and testing (20%, N = 250), and 375 patients from the Tongji Hospital (Wuhan, China) data were used for testing. Intervention: None. Measurements and Main Results: Longitudinal clinical variables were analyzed as a function of days from outcome with time-lock-to-day of death (non-survivors) or discharge (survivors). A predictive model using the significant earliest predictors was constructed. Performance was evaluated using receiver operating characteristics area under the curve (AUC). The predictive model found lactate dehydrogenase, lymphocytes, procalcitonin, D-dimer, C-reactive protein, respiratory rate, and white-blood cells to be early predictors of mortality. The AUC for the zero to 9 days prior to outcome were: 0.99, 0.96, 0.94, 0.90, 0.82, 0.75, 0.73, 0.77, 0.79, and 0.73, respectively (Stony Brook Hospital), and 1.0, 0.86, 0.88, 0.96, 0.91, 0.62, 0.67, 0.50, 0.63, and 0.57, respectively (Tongji Hospital). In comparison, prediction performance using hospital admission data was poor (AUC = 0.59). Temporal fluctuations of most clinical variables, indicative of physiological and biochemical instability, were markedly higher in non-survivors compared to survivors (p < 0.001). Conclusion: This study identified several clinical markers that demonstrated a temporal progression associated with mortality. These variables accurately predicted death within a few days prior to outcome, which provides objective indication that closer monitoring and interventions may be needed to prevent deterioration.

Dataset Information

Clinical and Molecular Characterization of Achromatopsia Patients: A Longitudinal Study.

Publications

Clinical and Molecular Characterization of Achromatopsia Patients: A Longitudinal Study.

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