학술논문
A Retrospective Longitudinal Study of 460 Patients with ABCA4-Associated Retinal Disease.
Document Type
Academic Journal
Author
Fenner BJ; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa; Singapore National Eye Centre; Singapore Eye Research Institute; and Ophthalmology and Visual Sciences Academic Clinical Programme, SingHealth Duke-NUS Academic Medical Centre, Duke-NUS Graduate Medical School, Singapore, Republic of Singapore.; Whitmore SS; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.; DeLuca AP; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.; Andorf JL; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.; Daggett HT; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.; Luse MA; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.; Haefeli LM; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.; Riley JB; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.; Critser DB; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.; Wilkinson ME; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.; Dumitrescu AV; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.; Drack AV; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.; Boyce TM; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.; Russell JF; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.; Binkley EM; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.; Sohn EH; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.; Russell SR; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.; Boldt HC; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.; Mullins RF; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.; Tucker BA; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.; Scheetz TE; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.; Han IC; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa.; Stone EM; The University of Iowa Institute for Vision Research and the Department of Ophthalmology and Visual Sciences, Carver College of Medicine, The University of Iowa, Iowa City, Iowa. Electronic address: edwin-stone@uiowa.edu.
Source
Publisher: Elsevier Country of Publication: United States NLM ID: 7802443 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1549-4713 (Electronic) Linking ISSN: 01616420 NLM ISO Abbreviation: Ophthalmology Subsets: MEDLINE
Subject
Language
English
Abstract
Purpose: To investigate the distribution of genotypes and natural history of ABCA4-associated retinal disease in a large cohort of patients seen at a single institution.
Design: Retrospective, single-institution cohort review.
Participants: Patients seen at the University of Iowa between November 1986 and August 2022 clinically suspected to have disease caused by sequence variations in ABCA4.
Methods: DNA samples from participants were subjected to a tiered testing strategy progressing from allele-specific screening to whole genome sequencing. Charts were reviewed, and clinical data were tabulated. The pathogenic severity of the most common alleles was estimated by studying groups of patients who shared 1 allele. Groups of patients with shared genotypes were reviewed for evidence of modifying factor effects.
Main Outcome Measures: Age at first uncorrectable vision loss, best-corrected visual acuity, and the area of the I2e isopter of the Goldmann visual field.
Results: A total of 460 patients from 390 families demonstrated convincing clinical features of ABCA4-associated retinal disease. Complete genotypes were identified in 399 patients, and partial genotypes were identified in 61. The median age at first vision loss was 16 years (range, 4-76 years). Two hundred sixty-five families (68%) harbored a unique genotype, and no more than 10 patients shared any single genotype. Review of the patients with shared genotypes revealed evidence of modifying factors that in several cases resulted in a > 15-year difference in age at first vision loss. Two hundred forty-one different alleles were identified among the members of this cohort, and 161 of these (67%) were found in only a single individual.
Conclusions: ABCA4-associated retinal disease ranges from a very severe photoreceptor disease with an onset before 5 years of age to a late-onset retinal pigment epithelium-based condition resembling pattern dystrophy. Modifying factors frequently impact the ABCA4 disease phenotype to a degree that is similar in magnitude to the detectable ABCA4 alleles themselves. It is likely that most patients in any cohort will harbor a unique genotype. The latter observations taken together suggest that patients' clinical findings in most cases will be more useful for predicting their clinical course than their genotype.
Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
(Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
Design: Retrospective, single-institution cohort review.
Participants: Patients seen at the University of Iowa between November 1986 and August 2022 clinically suspected to have disease caused by sequence variations in ABCA4.
Methods: DNA samples from participants were subjected to a tiered testing strategy progressing from allele-specific screening to whole genome sequencing. Charts were reviewed, and clinical data were tabulated. The pathogenic severity of the most common alleles was estimated by studying groups of patients who shared 1 allele. Groups of patients with shared genotypes were reviewed for evidence of modifying factor effects.
Main Outcome Measures: Age at first uncorrectable vision loss, best-corrected visual acuity, and the area of the I2e isopter of the Goldmann visual field.
Results: A total of 460 patients from 390 families demonstrated convincing clinical features of ABCA4-associated retinal disease. Complete genotypes were identified in 399 patients, and partial genotypes were identified in 61. The median age at first vision loss was 16 years (range, 4-76 years). Two hundred sixty-five families (68%) harbored a unique genotype, and no more than 10 patients shared any single genotype. Review of the patients with shared genotypes revealed evidence of modifying factors that in several cases resulted in a > 15-year difference in age at first vision loss. Two hundred forty-one different alleles were identified among the members of this cohort, and 161 of these (67%) were found in only a single individual.
Conclusions: ABCA4-associated retinal disease ranges from a very severe photoreceptor disease with an onset before 5 years of age to a late-onset retinal pigment epithelium-based condition resembling pattern dystrophy. Modifying factors frequently impact the ABCA4 disease phenotype to a degree that is similar in magnitude to the detectable ABCA4 alleles themselves. It is likely that most patients in any cohort will harbor a unique genotype. The latter observations taken together suggest that patients' clinical findings in most cases will be more useful for predicting their clinical course than their genotype.
Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
(Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)