Best Vitelliform Macular Dystrophy Natural History Study Report 2: Fundus Autofluorescence and Optical Coherence Tomography.

Purpose: To analyze the retinal imaging findings and natural history of Best vitelliform macular dystrophy (BVMD).

Design: Single-center retrospective, consecutive, observational study.

Participants: Patients with a clinical diagnosis of BVMD, from pedigrees with a likely disease-causing monoallelic variant in BEST1.

Bi-allelic variants in three genes encoding distinct subunits of the vesicular AP-5 complex cause hereditary macular dystrophy.

Inherited retinal diseases (IRDs) are a genetically heterogeneous group of Mendelian disorders that often lead to progressive vision loss and involve approximately 300 distinct genes. Although variants in these loci account for the majority of molecular diagnoses, other genes associated with IRD await molecular identification. In this study, we uncover bi-allelic assortments of 23 different (22 loss-of-function) variants in AP5Z1, AP5M1, and AP5B1 as independent causes of recessive IRD in members of 19 families from nine countries.

Biallelic null variants in C19orf44 cause a unique late onset retinal dystrophy phenotype characterized by patchy perifoveal chorioretinal atrophy.

Purpose: To identify the genetic cause for disease in individuals affected with inherited retinal disease (IRD), to characterize their retinal phenotype and the properties of the underlying gene.

Methods: Participants underwent a comprehensive ophthalmological evaluation, including best-corrected visual acuity, visual field testing, fundus autofluorescence, optical coherence tomography and electroretinography. Genetic analyses included exome, genome and Sanger sequencing.

Values, Preferences, and Risk Tolerance of People Waitlisted for a Kidney Transplant Regarding Potential Deceased Donor Organ Profiles: A Systematic Review.

Background: Incorporating the views of people waitlisted for a kidney transplant is important when clinicians consider any donor kidney offer.

Methods: We conducted a systematic review of quantitative and qualitative studies in adult patients on, or under assessment for, the kidney waitlist. We focused on views of extended criteria, increased viral (blood-borne virus), or increased cancer risk in deceased donor kidneys.

Rare disease gene association discovery in the 100,000 Genomes Project.

Up to 80% of rare disease patients remain undiagnosed after genomic sequencing, with many probably involving pathogenic variants in yet to be discovered disease-gene associations. To search for such associations, we developed a rare variant gene burden analytical framework for Mendelian diseases, and applied it to protein-coding variants from whole-genome sequencing of 34,851 cases and their family members recruited to the 100,000 Genomes Project. A total of 141 new associations were identified, including five for which independent disease-gene evidence was recently published.