Protocol for Health Risk Information Technology-Assisted Genetic Evaluation (HeRITAGE): a randomised controlled trial of digital genetic cancer risk assessment in a diverse underserved gynaecology clinic.

Introduction: In the USA, up to 95% of individuals harbouring cancer-predisposing germline pathogenic variants have not been identified despite recommendations for screening at the primary care level.

Methods And Analysis: Our primary objective is to use a two-arm, single-institution randomised controlled trial to compare the proportion of eligible patients that are recommended genetic testing for hereditary cancer syndromes using a digital tool versus clinician interview for genetic cancer risk assessment in an urban academic gynaecology clinic. New gynaecology patients will be consented and randomised 1:1 to either the intervention arm, in which a digital tool is used for genetic cancer risk assessment, or usual care, in which the clinician performs genetic cancer risk assessment.

Integration and usability of a digital cancer risk stratification tool to optimize identification of patients at risk for hereditary cancers: A pilot study.

Background: Patients with a personal or family history of cancer may have elevated risk of developing future cancers, which often remains unrecognized due to lapses in screening. This pilot study assessed the usability and clinical outcomes of a cancer risk stratification tool in a gynecologic oncology clinic.

Methods: New gynecologic oncology patients were prompted to complete a commercially developed personal and family history-based risk stratification tool to assess eligibility for genetic testing using National Comprehensive Cancer Network criteria and estimated lifetime breast cancer risk using the Tyrer-Cuzick model.

Chatbot Artificial Intelligence for Genetic Cancer Risk Assessment and Counseling: A Systematic Review and Meta-Analysis.

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.

Venous Tortuosity in -Associated Gould Syndrome.

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.

Generation of CRB1 RP Patient-Derived iPSCs and a CRISPR/Cas9-Mediated Homology-Directed Repair Strategy for the CRB1 c.2480G>T Mutation.

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.

Generation of an Avian Myeloblastosis Virus (AMV) Reverse Transcriptase Prime Editor.

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.

Do people with hereditary cancer syndromes inform their at-risk relatives? A systematic review and meta-analysis.

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).

Patient perspectives on risk-reducing salpingectomy with delayed oophorectomy for ovarian cancer risk-reduction: A systematic review of the literature.

Objective: Increasing evidence suggests the fallopian tube as the site of origin of BRCA1/2-associated high-grade ovarian cancers. Several ongoing trials are evaluating salpingectomy with delayed oophorectomy (RRSDO) for ovarian cancer risk reduction and patients are beginning to ask their clinicians about this surgical option. This study sought to systematically review the available literature examining patient preferences regarding RRSDO and risk-reducing salpingo-oophorectomy (RRSO) to provide clinicians with an understanding of patient values, concerns, and priorities surrounding ovarian cancer risk-reducing surgery.

Web-based tool for cancer family history collection: A prospective randomized controlled trial.

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.

Clinical and Therapeutic Evaluation of the Ten Most Prevalent Mutations.

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.

Culture of Human Retinal Explants for Ex Vivo Assessment of AAV Gene Delivery.

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.

Generation of Human iPSC-Derived Retinal Organoids for Assessment of AAV-Mediated Gene Delivery.

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.

Metabolite Extraction from RPE Cells and Retinas Related to Retinitis Pigmentosa.

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.

CRISPR Manipulations in Stem Cell Lines.

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.

Multimodal imaging reveals retinoschisis masquerading as retinal detachment in patients with choroideremia.

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.

Expanding the phenotype of TTLL5-associated retinal dystrophy: a case series.

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.