A Carrier Female Manifesting an Unusual X-Linked Retinoschisis Phenotype Associated with the Pathogenic Variant c.266delA, p.(Tyr89LeufsTer37) in , and Skewed X-Inactivation.

X-linked retinoschisis (XLRS) is the most common juvenile macular degeneration in males. Unlike most other X-linked retinal dystrophies, carrier heterozygous females are very rarely reported to show clinical features of the disease. Herein, we describe unusual retinal features in a 2-year-old female infant with family history and genetic testing consistent with XLRS.

Intraretinal Microvascular Abnormalities and Venous Beading Have Different Genetic Profiles in Caucasian Patients with Non-Proliferative Diabetic Retinopathy.

Diabetic Retinopathy (DR) is a leading cause of preventable visual impairment in the working age population. Despite the increasing prevalence of DR, there remain gaps in our understanding of its pathophysiology. This is a prospective case-control study comparing the genetic profiles of patients with no DR vs.

Phenotypic and Genetic Characteristics in a Cohort of Patients with Usher Genes.

Background: This study aimed to compare phenotype−genotype correlation in patients with Usher syndrome (USH) to those with autosomal recessive retinitis pigmentosa (NS-ARRP) caused by genes associated with Usher syndrome. Methods: Case notes of patients with USH or NS-ARRP and a molecularly confirmed diagnosis in genes associated with Usher syndrome were reviewed. Phenotypic information, including the age of ocular symptoms, hearing impairment, visual acuity, Goldmann visual fields, fundus autofluorescence (FAF) imaging and spectral domain optical coherence tomography (OCT) imaging, was reviewed.

The role of multimodal imaging and vision function testing in -related retinopathies and their relevance to future therapeutic interventions.

The aim of this review article is to describe the specific features of Stargardt disease and retinopathies (ABCA4R) using multimodal imaging and functional testing and to highlight their relevance to potential therapeutic interventions. Standardised measures of tissue loss, tissue function and rate of change over time using formal structured deep phenotyping in Stargardt disease and ABCA4R are key in diagnosis, and prognosis as well as when selecting cohorts for therapeutic intervention. In addition, a meticulous documentation of natural history will be invaluable in the future to compare treated with untreated retinas.

Whole genome sequencing in a Knobloch syndrome family confirms the molecular diagnosis.

Background: To establish the molecular diagnosis in two brothers presenting with the ocular features of Knobloch Syndrome using whole genome sequencing (WGS).

Methods: Clinical examination and ophthalmological phenotyping were completed under general anaesthesia. DNA samples were tested on a targeted retinal dystrophy next-generation sequencing panel.

An Overview of the Genetics of Retinopathies, an Evolving Story.

Stargardt disease (STGD1) and retinopathies (ABCA4R) are caused by pathogenic variants in the gene inherited in an autosomal recessive manner. The gene encodes an importer flippase protein that prevents the build-up of vitamin A derivatives that are toxic to the RPE. Diagnosing ABCA4R is complex due to its phenotypic variability and the presence of other inherited retinal dystrophy phenocopies.

SPIKE-1: A Randomised Phase II/III trial in a community setting, assessing use of camostat in reducing the clinical progression of COVID-19 by blocking SARS-CoV-2 Spike protein-initiated membrane fusion.

Objectives: The primary objective is to evaluate the efficacy of camostat to prevent respiratory deterioration in patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Secondary objectives include assessment of the ability of camostat to reduce the requirement for Coronavirus disease 2019 (COVID-19) related hospital admission and to reduce the requirement for supplementary oxygen and ventilation as treatment for SARS-CoV-2 infection, to evaluate overall mortality related to COVID-19 and to evaluate the efficacy of camostat by effect on clinical improvement. Research objectives include to assess change in COVID-19 symptom severity, to evaluate the ability of camostat to reduce viral load throughout duration of illness as well as translational research on host and viral genomics, serum antibody production, COVID-19 diagnostics, and validation of laboratory testing methods and biomarkers.

Targeted next generation sequencing and family survey enable correct genetic diagnosis in CRX associated macular dystrophy - a case report.

Background: We present 3 members of a family with macular dystrophy, originally diagnosed as Stargardt disease, with a significantly variable age at onset, caused by a heterozygous mutation in CRX.

Case Presentation: A 43-year-old female with bull's eye maculopathy, whose sister was diagnosed with Stargardt disease previously at another centre, was found to have a single ABCA4 variant. Further examination of the family revealed that the asymptomatic father was also affected, indicating a dominant pattern of inheritance.

Genetic and Clinical Findings in an Ethnically Diverse Cohort with Retinitis Pigmentosa Associated with Pathogenic Variants in CERKL.

Autosomal recessive retinitis pigmentosa is caused by mutations in over 40 genes, one of which is the ceramide kinase-like gene (). We present a case series of six patients from six unrelated families diagnosed with inherited retinal dystrophies (IRD) and with two variants in recruited from a multi-ethnic British population. A retrospective review of clinical data in these patients was performed and included colour fundus photography, fundus autofluorescence (AF) imaging, spectral domain-optical coherence tomography (SD-OCT), visual fields and electroretinogram (ERG) assessment where available.

Novel Pathogenic Sequence Variants in and Clinical Findings in Three Patients.

A retrospective review of the clinical records of patients seen at the Oxford Eye Hospital identified as having mutations was performed. The data included symptoms, best-corrected visual acuity, multimodal retinal imaging, visual fields and electrophysiology testing. Three participants were identified with biallelic pathogenic sequence variants detected using a targeted NGS gene panel, two of which were novel.

From Africa to the USA: A Combined Strategy for Nursing Education.

Engaging students in class when first-hand experience is not available is challenging. Three teaching strategies, flipped classroom, a guest speaker, and technology, engaged students during a global health class. Students were given a graded preclass assignment, which was used to guide the class session when an expert physician from Zambia joined us using technology.

"Genetic and clinical findings in an ethnically diverse retinitis pigmentosa cohort associated with pathogenic variants in EYS".

Background And Objectives: The EYS gene is an important cause of autosomal recessive retinitis pigmentosa (arRP). The objective of this study is to report on novel pathogenic variants in EYS and the range of associated phenotypes.

Subjects And Methods: This retrospective case series at a tertiary referral centre for inherited retinal diseases describes patients with an IRD and at least two variants in the EYS gene.

How gains for SRHR in the UN have remained possible in a changing political climate.

As right-wing populist movements make electoral gains around the world, one might expect that resultant policy and legislative reversals against sexual and reproductive health and rights (SRHR) would be mirrored by a similar backlash in United Nations (UN) human rights negotiations. Yet the past five years have seen unprecedented advances for SRHR within the UN Human Rights Council (HRC), treaty bodies, and special procedures. In this article, we provide an overview of SRHR gains and setbacks within the HRC and analyse their broader significance, particularly as socially conservative nation states and non-governmental organisations seek to challenge them.

Association of Clinical and Genetic Heterogeneity With BEST1 Sequence Variations.

Importance: Detailed phenotypic information on the spectrum of fundus abnormalities and clinical variability of all phenotypes associated with sequence variations in BEST1 is limited.

Objective: To report a detailed phenotypic and genetic analysis of a patient cohort with sequence variations in BEST1.

Design, Setting, And Participants: This retrospective case series took place at the Oxford Eye Hospital in Oxford, UK.

Correction: A case of malignant hyperlactaemic acidosis appearing upon treatment with the mono-carboxylase transporter 1 inhibitor AZD3965.

Since the publication of this paper the authors noticed an error in the listed authors, where Alexandros Siskos was listed as Alexandros Sitkos. This has now been corrected.

A case of malignant hyperlactaemic acidosis appearing upon treatment with the mono-carboxylase transporter 1 inhibitor AZD3965.

A 47-year-old man with metastatic melanoma presented with refractory hyperlactaemic acidosis following the first dose of the mono-carboxylase transporter 1 inhibitor AZD3965 within a "first time in man" clinical trial. The mechanism of the agent and the temporal relationship suggested that this event was potentially drug related and recruitment was suspended. However, urinary metabolomics showed extensive abnormalities even prior to drug administration, leading to investigations for an underlying metabolic disorder.

Targeted deletion of an NRL- and CRX-regulated alternative promoter specifically silences FERM and PDZ domain containing 1 (Frmpd1) in rod photoreceptors.

Regulation of cell type-specific gene expression is critical for generating neuronal diversity. Transcriptome analyses have unraveled extensive heterogeneity of transcribed sequences in retinal photoreceptors because of alternate splicing and/or promoter usage. Here we show that Frmpd1 (FERM and PDZ domain containing 1) is transcribed from an alternative promoter specifically in the retina.

Novel homozygous splicing mutations in cause autosomal recessive retinitis pigmentosa.

Purpose: Mutations in encoding ADP-ribosylation factor-like 2 binding protein, have recently been implicated as a cause of autosomal recessive retinitis pigmentosa (arRP), with three homozygous variants identified to date. In this study, we performed next-generation sequencing to reveal additional arRP cases associated with variants.

Methods: Whole-genome sequencing (WGS) or whole-exome sequencing (WES) was performed in 1,051 unrelated individuals recruited for the UK Inherited Retinal Disease Consortium and NIHR-BioResource Rare Diseases research studies.