Publications by authors named "Sarah R Levi"

Article Synopsis
  • This study investigates genetic variants linked to outer retinal tubulation (ORT) by analyzing the prevalence and clinical consequences of ORT in patients with inherited retinal diseases (IRDs).
  • A cohort of 565 IRD patients underwent SD-OCT imaging, revealing that 104 exhibited ORT, primarily associated with specific genetic variants, especially in RPE-specific and some non-RPE-specific genes.
  • The findings show a strong correlation between ORT presence and IRDs caused by RPE-specific and non-RPE-specific genes, while no cases of ORT were found in patients with photoreceptor-specific gene variants.
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Purpose: Most individuals with a hereditary cancer syndrome are unaware of their genetic status to underutilization of hereditary cancer risk assessment. Chatbots, or programs that use artificial intelligence to simulate conversation, have emerged as a promising tool in health care and, more recently, as a potential tool for genetic cancer risk assessment and counseling. Here, we evaluated the existing literature on the use of chatbots in genetic cancer risk assessment and counseling.

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  • - The study investigates the link between germline pathogenic variants in the PALB2 gene and the development of ovarian cancer, given that 20% of ovarian cancers are hereditary.
  • - A systematic review and meta-analysis were conducted, analyzing 55 studies with data from nearly 48,194 ovarian cancer patients, revealing that only 0.4% had PALB2 pathogenic variants.
  • - The findings suggest that individuals with ovarian cancer are 2.48 times more likely to carry PALB2 pathogenic variants compared to the general population, indicating the need for further research on this gene's role in ovarian cancer.
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Mutations in collagen-encoding genes have been linked to numerous systemic diseases. Specifically, pathologic alterations in have been linked to Gould syndrome, a hereditary angiopathy affecting the brain, kidneys, and eyes. However, the ocular phenotype associated with -associated disease has yet to be fully characterized.

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Mutations in the Crumbs-homologue-1 (CRB1) gene lead to a spectrum of severe inherited retinal diseases, including retinitis pigmentosa (RP). The establishment of a genotype-phenotype correlation in CRB1 patients has been difficult due to the substantial variability and phenotypic overlap between CRB1-associated diseases. This phenotypic modulation may be due to several factors, including genetic modifiers, deep intronic mutations, isoform diversity, and copy number variations.

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Prime editing (PE) is a novel, double-strand break (DSB)-independent gene editing technology that represents an exciting avenue for the treatment of inherited retinal diseases (IRDs). Given the extensive and heterogenous nature of the 280 genes associated with IRDs, genome editing has presented countless complications. However, recent advances in genome editing technologies have identified PE to have tremendous potential, with the capability to ameliorate small deletions and insertions in addition to all twelve possible transition and transversion mutations.

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Purpose: To evaluate rates of familial disclosure of hereditary cancer syndrome information.

Methods: A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines (PROSPERO no.: CRD42020134276).

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Objectives: Approximately 1% of individuals have a hereditary cancer predisposition syndrome, however, the majority are not aware. Collecting a cancer family history (CFH) can triage patients to receive genetic testing. To rigorously assess different methods of CFH collection, we compared a web-based tool (WBT) to usual care (clinician collects CFH) in a randomized controlled trial.

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Mutations in the () gene lead to severe inherited retinal dystrophies (IRDs), accounting for nearly 80,000 cases worldwide. To date, there is no therapeutic option for patients suffering from -IRDs. Therefore, it is of great interest to evaluate gene editing strategies capable of correcting mutations.

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Article Synopsis
  • * CRISPR technology, particularly the recently approved EDIT-101, shows promise for treating IRDs by targeting genetic mutations, such as those in the CEP290 gene that cause Leber congenital amaurosis.
  • * This study explores prime editing as a cutting-edge method to correct specific mutations, demonstrating its potential through experiments on a mouse model with a mutation that leads to retinitis pigmentosa.
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Due to the clinically established safety and efficacy profile of recombinant adeno-associated viral (rAAV) vectors, they are considered the "go to" vector for retinal gene therapy. Design of a rAAV-mediated gene therapy focuses on cell tropism, high transduction efficiency, and high transgene expression levels to achieve the lowest therapeutic treatment dosage and avoid toxicity. Human retinal explants are a clinically relevant model system for exploring these aspects of rAAV-mediated gene delivery.

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Human retinal organoids derived from induced pluripotent stem cells (iPSCs) serve as a promising preclinical model for testing the safety and efficacy of viral gene therapy. Retinal organoids recapitulate the stratified multilayered epithelium structure of the developing and maturating human retina. As such, retinal organoids are unique tools to model retinal disease and to test therapeutic interventions toward their amelioration.

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The application of metabolomics in ophthalmology helps to identify new biomarkers and elucidate disease mechanisms in different eye diseases, as well as aiding in the development of potential treatment options. Extracting metabolites successfully is essential for potential further analysis using mass spectrometry. In this chapter, we describe how to extract metabolites from a variety of sources including (1) cells on a dish, (2) cell culture medium, and (3) tissues in vivo with and without stable isotope tracers.

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Insights into genome engineering in cells have allowed researchers to cultivate and modify cells as organoids that display structural and phenotypic features of human diseases or normal health status. The generation of targeted mutants is a crucial step toward studying the biomedical effect of genes of interest. Modified organoids derived from patients' tissue cells are used as models to study diseases and test novel drugs.

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Article Synopsis
  • Cascade genetic testing for hereditary cancer syndromes helps at-risk relatives access cancer screenings and preventive surgeries, reducing health risks while improving overall quality of life.
  • In a pilot study involving 95 participants, two years later, 76% followed up, and 44% of those found a genetic mutation were able to pursue recommended cancer screenings and surgeries.
  • Results displayed low anxiety and depression levels among participants, indicating that clinician-facilitated cascade testing is beneficial and should be further explored in larger studies.
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  • Bietti crystalline dystrophy (BCD) is a rare disorder that can cause blindness, making it important to track its progression effectively.
  • A study analyzed patients with BCD by comparing various measurements from optical coherence tomography to their best corrected visual acuity.
  • The findings suggested that certain structural measurements, like foveolar thickness and outer nuclear layer area, correlate with better visual acuity, highlighting the need for further research to refine outcome measurements for this condition.*
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  • The study looked for specific proteins in the eyes of patients with autoimmune retinopathy (AIR) to help diagnose the condition better.
  • Researchers compared eye samples from AIR patients to those with other eye issues, using special tests to find protein differences.
  • They found several proteins that were higher or lower in AIR patients, and one key protein called NrCAM may be important for diagnosis in the future.
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  • The study aims to compare the effects of hereditary optic neuropathies (e.g., LHON, OPA1, OPA13) on retinal photoreceptors and ganglion cells, focusing on mitochondrial dysfunction.
  • A retrospective evaluation of patients included assessments like visual acuity, imaging, and visual responses, revealing common characteristics in the examined optic neuropathies.
  • Results showed that retinal ganglion cells generally suffer first from mitochondrial dysfunction, while photoreceptor dysfunction varies, particularly significant in OPA13 after ganglion cell degeneration.
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Purpose: To report three cases of retinoschisis in patients with intermediate to advanced choroideremia.

Observations: Three patients were referred for evaluation of retinal detachment in the context of an inherited retinal degenerative disease. In all three cases, patients carried variants in the gene suspected to be pathogenic and exhibited the characteristic findings of choroideremia, including pigment clumping and chorioretinal atrophy with scleral exposure and prominent choroidal vessels.

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Background: Inherited retinal dystrophies describe a heterogeneous group of retinal diseases that lead to the irreversible degeneration of rod and cone photoreceptors and eventual blindness. Recessive loss-of-function mutations in Tubulin Tyrosine Ligase Like 5 (TTLL5) represent a recently described cause of inherited cone-rod and cone dystrophy. This study describes the unusual phenotypes of three patients with autosomal recessive mutations in TTLL5.

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Article Synopsis
  • * The mechanisms behind RGC degeneration are not fully understood but involve oxidative stress and mitochondrial dysfunction, which also play roles in other neurodegenerative disorders.
  • * The review covers various ocular conditions linked to RGC degeneration, experimental research methods, and explores antioxidants as a potential therapeutic strategy.
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Ciliopathies are a group of genetic dystrophies causing syndromic and non-syndromic retinal degeneration. We identified as the causative gene in a patient with childhood-onset retinal dystrophy without other systemic symptoms at the age of 20. This 20-year-old man presented with cone-rod dystrophy and homozygous in-frame duplication variants (c.

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Inherited retinal diseases (IRDs) are chronic, hereditary disorders that lead to progressive degeneration of the retina. Disease etiology originates from a genetic mutation-inherited or -with a majority of IRDs resulting from point mutations. Given the plethora of IRDs, to date, mutations that cause these dystrophies have been found in approximately 280 genes.

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