A5034463469- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Glaucoma and retinal disorders
- Photoreceptor and optogenetics research
- Cell Adhesion Molecules Research
- Complement system in diseases
- Connexins and lens biology
- Cellular transport and secretion
- Retinal and Macular Surgery
- Retinal Imaging and Analysis
- RNA regulation and disease
- Mitochondrial Function and Pathology
- Retinopathy of Prematurity Studies
- Ocular Diseases and Behçet’s Syndrome
- melanin and skin pigmentation
- Advanced biosensing and bioanalysis techniques
- Retinal and Optic Conditions
- Retinoids in leukemia and cellular processes
- Adenosine and Purinergic Signaling
- Mosquito-borne diseases and control
- Renal Diseases and Glomerulopathies
- Phosphodiesterase function and regulation
- Molecular Biology Techniques and Applications
- Cholesterol and Lipid Metabolism
- Drug-Induced Ocular Toxicity
Columbia University
2015-2024
Columbia University Irving Medical Center
2018-2024
New America
2019
Ophthalmology Associates (United States)
2005-2017
University of California, Santa Barbara
2005
Queen's University Belfast
2005
University of Iowa
2005
Asper Biotech (Estonia)
2002-2003
Estonian Biocentre
1999-2002
University of Tartu
2002
Age-related macular degeneration (AMD) is the most frequent cause of irreversible blindness in elderly developed countries. Our previous studies implicated activation complement formation drusen, hallmark lesion AMD. Here, we show that factor H (HF1), major inhibitor alternative pathway, accumulates within drusen and synthesized by retinal pigmented epithelium. Because linkage analyses identified chromosome 1q25-32, which harbors gene ( HF1 / CFH ), as an AMD susceptibility locus, analyzed...
Genetic variation in the ABCR (ABCA4) gene has been associated with five distinct retinal phenotypes, including Stargardt disease/fundus flavimaculatus (STGD/FFM), cone-rod dystrophy (CRD), and age-related macular degeneration (AMD). Comparative genetic analyses of diagnostics have complicated by substantial allelic heterogeneity differences screening methods. To overcome these limitations, we designed a genotyping microarray (gene chip) for that includes all ∼400 disease-associated other...
Variants in the complement factor H gene (CFH) are associated with age-related macular degeneration (AMD). CFH and five CFH-related genes (CFHR1-5) lie within regulators of activation (RCA) locus on chromosome 1q32. Aims Methods. In this study, structural evolutionary relationships between these AMD was refined using a combined genetic, molecular immunohistochemical approach.We identify characterize large, common deletion that encompasses both CFHR1 CFHR3 genes. CFHR1, an abundant serum...
To quantify fundus autofluorescence (qAF) in patients with recessive Stargardt disease (STGD1).A total of 42 STGD1 (ages: 7-52 years) at least one confirmed disease-associated ABCA4 mutation were studied. Fundus AF images (488-nm excitation) acquired a confocal scanning laser ophthalmoscope equipped an internal fluorescent reference to account for variable power and detector sensitivity. The gray levels (GLs) each image calibrated the reference, zero GL, magnification, normative optical...
Background Variation in the ABCA4 gene is causal for, or associated with, a wide range of phenotypes from early onset Mendelian retinal dystrophies to late-onset complex disorders such as age-related macular degeneration (AMD). Despite substantial progress determining genetic variation, even complete sequencing entire open reading frame and splice sites identifies biallelic mutations only 60%–70% cases; 20%–25% remain with one mutation no are found 10%–15% cases clinically confirmed disease....
To describe the clinical and molecular characteristics of patients with childhood-onset Stargardt disease (STGD).Retrospective case series.Forty-two who were diagnosed STGD in childhood at a single institution between January 2001 2012.A detailed history comprehensive ophthalmic examination undertaken, including color fundus photography, autofluorescence imaging, spectral-domain optical coherence tomography (SD-OCT), pattern full-field electroretinograms. The entire coding region splice...
To find all possible disease-associated variants in coding sequences of the ABCA4 gene a large cohort patients diagnosed with ABCA4-associated diseases.One hundred sixty-eight who had been clinically Stargardt disease, cone-rod dystrophy, and other phenotypes were prescreened for mutations microarray, resulting finding 1 2 expected 111 0 57 patients. The next-generation sequencing (NGS) strategy was applied to these sequence entire region splice sites gene. Identified new confirmed or...
Autosomal recessive Stargardt disease (STGD1, MIM 248200) is caused by mutations in the ABCA4 gene. Complete sequencing of STGD patients identifies compound heterozygous or homozygous disease-associated alleles 65–70% and only one mutation 15–20% patients. This study was designed to find missing disease-causing variation a combination next-generation (NGS), array-Comparative Genome Hybridization (aCGH) screening, familial segregation silico analyses. The entire 140 kb genomic locus sequenced...
Purpose: We evaluated the incongruous observation whereby flecks in recessive Stargardt disease (STGD1) can exhibit increased short-wavelength autofluorescence (SW-AF) that originates from retinal pigment epithelium (RPE) lipofuscin, while near-infrared AF (NIR-AF), emitted primarily RPE melanin, is usually reduced or absent at fleck positions. Methods: Flecks SW- and NIR-AF images spectral-domain optical coherence tomography (SD-OCT) scans were studied 19 STGD1 patients carrying...
Leber congenital amaurosis (LCA) is an early-onset inherited disorder of childhood blindness characterized by visual impairment noted soon after birth. Variants in at least six genes (AIPL1, CRB1, CRX, GUCY2D, RPE65, and RPGRIP1) have been associated with a diagnosis consistent LCA or retinitis pigmentosa (RP). Genetically heterogeneous inheritance complicates the analyses cases, especially patients without family history disorder, conventional methods are limited value.To overcome these...
We evaluated the pathogenicity of G1961E mutation in ABCA4 gene, and present range retinal phenotypes associated with this homozygosity a patient cohort ABCA4-associated phenotypes.Patients were enrolled from disease database at Columbia University or by inquiry collaborating physicians. Only patients homozygous for enrolled. The entire gene open reading frame, including all exons flanking intronic sequences, was sequenced patients. Phenotype data obtained clinical history examination,...
Purpose.: Short-wavelength (SW) fundus autofluorescence (AF) is considered to originate from lipofuscin in retinal pigment epithelium (RPE) and near-infrared (NIR) AF melanin. In patients with recessive Stargardt disease (STGD1), we correlated SW-AF NIR-AF structural information obtained by spectral-domain optical coherence tomography (SD-OCT). Methods.: Twenty-four STGD1 (45 eyes; age 8 61 years) carrying confirmed disease-associated ABCA4 mutations were studied prospectively. AF, NIR-AF,...
Autosomal recessive Stargardt disease (STGD1, MIM 248200) is caused by mutations in the ABCA4 gene. Complete sequencing of locus STGD1 patients identifies two expected disease-causing alleles ∼75% and only one mutation ∼15% patients. Recently, many possibly pathogenic variants deep intronic sequences have been identified latter group. We extended our analyses determined that these, c.4253+43G>A (rs61754045), present 29/1155 (2.6%) The variant found at statistically significantly higher...
Over 1200 variants in the ABCA4 gene cause a wide variety of retinal disease phenotypes, best known which is autosomal recessive Stargardt (STGD1). Disease-causing variation encompasses all mutation categories, from large copy number to very mild, hypomorphic missense variants. The most prevalent disease-causing variant, present ~ 20% cases European descent, c.5882G > A p.(Gly1961Glu), has been subject controversy since its minor allele frequency (MAF) as high 0.1 certain populations,...
Identification of mutations in the tumor suppressor gene TP53 has implications for molecular epidemiology and pathology human cancer. We have developed evaluated an arrayed primer extension assay covering both strands a region coding sequence containing more than 95% described so far TP53. On average, 97.5% can be analyzed from either sense or antisense strands, 81% strands. A patient DNA sample is amplified annealed to primers, which then promote polymerase reactions with four fluorescently...
To describe pathologic changes of the external limiting membrane (ELM) in young patients with early-onset Stargardt (STGD1) disease.Twenty-six STGD1 aged younger than 20 years confirmed disease-causing adenosine triphosphate-binding cassette, subfamily A, member 4 (ABCA4) alleles and 30 age-matched unaffected individuals were studied. Spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (AF), color photography (CFP) images, as well full-field electroretinograms...
To assess whether quantitative fundus autofluorescence (qAF), a measure of RPE lipofuscin, and spectral-domain optical coherence tomography (SD-OCT) can aid in the differentiation patients with features that could either be related to ABCA4 mutations or part phenotypic spectrum pattern dystrophies.Autofluorescence images (30°, 488-nm excitation) from 39 (67 eyes) were acquired confocal scanning laser ophthalmoscope equipped an internal fluorescent reference quantified as previously...
NR2E3, a photoreceptor-specific nuclear receptor (PNR), represses cone-specific genes and activates several rod-specific genes. In humans, mutations in NR2E3 have been associated with the recessively-inherited enhanced short-wavelength sensitive S-cone syndrome (ESCS) and, recently, autosomal dominant (ad) retinitis pigmentosa (RP) (adRP). present work, we describe two additional families affected by adRP that carry heterozygous c.166G>A (p.G56R) mutation gene. Functional analysis determined...