https://scholars.lib.ntu.edu.tw/handle/123456789/567487
Title: | Genotypes predispose phenotypes—clinical features and genetic spectrum of abca4-associated retinal dystrophies | Authors: | Sung Y.-C. CHANG-HAO YANG CHUNG-MAY YANG CHAO-WEN LIN Huang D.-S. Huang Y.-S. FUNG-RONG HU PEI-LUNG CHEN TA-CHING CHEN |
Issue Date: | 2020 | Publisher: | MDPI AG | Journal Volume: | 11 | Journal Issue: | 12 | Start page/Pages: | 1-17 | Source: | Genes | Abstract: | The ABCA4 gene is one of the most common disease-causing genes of inherited retinal degeneration. In this study, we report different phenotypes of ABCA4-associated retinal dystrophies in the Taiwanese population, its clinical progression, and its relationship with genetic characteristics. Thirty-seven subjects were recruited and all patients underwent serial ophthalmic examinations at a single medical center. Fundus autofluorescence (FAF) images were quantified for clinical evaluation, and panel-based next-generation sequencing testing was performed for genetic diagnosis. Visual preservation, disease progression, and genotype–phenotype correlation were analyzed. In this cohort, ABCA4-associated retinal degeneration presented as Stargardt disease 1 (STGD1, 62.16%), retinitis pigmentosa (32.43%), and cone-rod dystrophy (5.41%). STGD1 could be further divided into central and dispersed types. In each phenotype, the lesion areas quantified by FAF increased with age (p < 0.01) and correlated with poorer visual acuity. However, three patients had the foveal sparing phenotype and had relatively preserved visual acuity. Forty-two ABCA4 variants were identified as disease-causing, with c.1804C>T (p.Arg602Trp) the most frequent (37.84%). Patients with a combination of severe/null variants could have more extensive phenotypes, such as arRP and dispersed STGD1. This is the first cohort study of ABCA4-associated retinal degeneration in Taiwan with wide spectrums of both genotypic and phenotypic characteristics. An extremely high prevalence of c.1804C>T, which has not been reported in East Asia before, was noted. The extensiveness of retinal involvement might be regarded as a spectrum of ABCA4-associated retinal dystrophies. Different types of genetic variations could lead to distinctive phenotypes, according to the coding impact of variants. ? 2020 by the authors. Licensee MDPI, Basel, Switzerland. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85097036243&doi=10.3390%2fgenes11121421&partnerID=40&md5=09e7fef520fe63697fc09665854371cc https://scholars.lib.ntu.edu.tw/handle/123456789/567487 |
ISSN: | 2073-4425 | DOI: | 10.3390/genes11121421 | SDG/Keyword: | retinal specific ATP binding cassette transporter; ABC transporter; ABCA4 protein, human; ABCA4 gene; adolescent; adult; age distribution; aged; Article; autofluorescence imaging; child; clinical article; clinical evaluation; clinical feature; cohort analysis; cone rod dystrophy; controlled study; disease course; eye examination; female; fundus autofluorescence imaging; genetic association; genetic variability; genotype phenotype correlation; high throughput sequencing; human; infant; male; mutational analysis; newborn; retina degeneration; retina dystrophy; retinitis pigmentosa; Stargardt disease; Taiwan; Taiwanese; visual acuity; diagnostic imaging; ethnic group; eye fundus; genetic association study; genetic heterogeneity; genetic predisposition; genetics; genotype; middle aged; pathology; physiology; preschool child; retina dystrophy; retina fovea; retinitis pigmentosa; Stargardt disease; visual system examination; young adult; Adolescent; Adult; Aged; ATP-Binding Cassette Transporters; Child; Child, Preschool; Cone-Rod Dystrophies; Diagnostic Techniques, Ophthalmological; Ethnic Groups; Female; Fovea Centralis; Fundus Oculi; Genetic Association Studies; Genetic Heterogeneity; Genetic Predisposition to Disease; Genotype; High-Throughput Nucleotide Sequencing; Humans; Male; Middle Aged; Retinal Dystrophies; Retinitis Pigmentosa; Stargardt Disease; Taiwan; Young Adult |
Appears in Collections: | 醫學系 |
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