Novel BEST1 Variant Characterization in a Large French Cohort in Light of Updated Bestrophin-1 Structure-Function Correlation.

Purpose: To update knowledge on bestrophin-1 structure and function with the aim of assessing the pathogenicity of variants reported in the Leiden Open Variation Database (LOVD) and in a large French cohort of bestrophinopathies.

Methods: All unique variants reported in the latest version (October 2024) of the BEST1-LOVD database were uploaded and curated. We described all BEST1 variants identified in French patients analyzed at Lille University Hospital, between 2008 and 2024.

Generation of a human iPSC line, INMi007-A, carrying compound heterozygous DCT variants associated with oculocutaneous albinism type 8.

Pathogenic variants in the Dopachrome tautomerase (DCT) gene (NM_001129889.2) have recently been associated with a novel oculocutaneous albinism (OCA) subgroup, type 8 (OCA8). Here, we report the establishment of an induced pluripotent stem cell (iPSC) line, INMi007-A, derived from the skin fibroblasts of an individual compound heterozygous for two pathogenic variants in DCT, using the non-integrative Sendai virus reprogramming method.

[Monogenic autoinflammatory uveitis].

Monogenic autoinflammatory uveitis belongs to the spectrum of monogenic autoinflammatory diseases. When early-onset uveitis is associated with specific extra-ocular manifestations, particularly in a familial or geographical context, it guides the clinician towards a diagnosis of a monogenic autoinflammatory disease. The clinical presentation and mode of inheritance will help identify the underlying cause, and the detection of a pathogenic variant will confirm the diagnosis and guide the management approach.

Identification of IDH3G, encoding the gamma subunit of mitochondrial isocitrate dehydrogenase, as a novel candidate gene for X-linked retinitis pigmentosa.

Purpose: Retinitis pigmentosa (RP) is a genetically heterogeneous group of retinal degenerative disorders characterized by the loss of rod and cone photoreceptors, leading to visual impairment and blindness. To date, to our knowledge, X-linked RP has been associated with variants in 3 genes (RPGR, RP2, and OFD1), whereas genetic defects at 3 loci (RP6, RP24, and RP34) are yet unidentified. The aim of this study was to identify a novel candidate gene underlying X-linked RP.

Voretigene neparvovec in RPE65-related inherited retinal dystrophy: the 1-year real-world study LIGHT.

Background: This retrospective real-world study evaluated the effectiveness and safety of subretinal voretigene neparvovec (VN) in French patients (six children, six adults) with inherited retinal dystrophies.

Methods: Data were collected from medical records for the year following bilateral treatment with subretinal VN. Functional vision was assessed using the Streetlab mobility course with obstacles.

Sodium valproate, a potential repurposed treatment for the neurodegeneration in Wolfram syndrome (TREATWOLFRAM): trial protocol for a pivotal multicentre, randomised double-blind controlled trial.

Introduction: Wolfram syndrome (Spectrum Disorder) is an ultra-rare monogenic form of progressive neurodegeneration and diabetes mellitus. In common with most rare diseases, there are no therapies to slow or stop disease progression. Sodium valproate, an anticonvulsant with neuroprotective properties, is anticipated to mediate its effect via alteration of cell cycle kinetics, increases in p21 expression levels and reduction in apoptosis and increase in Wolframin protein expression.

Elevated Plasma Complement Factors in CRB1-Associated Inherited Retinal Dystrophies.

Purpose: To determine the profile of inflammation-related proteins and complement system factors in the plasma of CRB1-associated inherited retinal dystrophies (CRB1-IRDs).

Methods: We used the Olink Explore 384 Inflammation II panel for targeted proteomics in 30 cases and 29 controls (cohort I) to identify immune pathways involved in CRB1-IRDs. Genotyping was performed in cohort I and a second cohort of 123 patients from 14 countries and 1292 controls (cohort II).

Interim estimates of vaccine effectiveness against influenza A(H1N1)pdm09 and A(H3N2) during a delayed influenza season, Canada, 2024/25.

The Canadian Sentinel Practitioner Surveillance Network (SPSN) reports interim 2024/25 vaccine effectiveness (VE) against acute respiratory illness due to laboratory-confirmed influenza during a delayed season of predominant A(H1N1)pdm09 and lower A(H3N2) co-circulation. Through mid-January, the risk of outpatient illness due to influenza A is reduced by about half among vaccinated vs unvaccinated individuals. Adjusted VE is 53% (95% CI: 36-65) against A(H1N1)pdm09, comprised of clades 5a.

De novo and inherited dominant variants in U4 and U6 snRNAs cause retinitis pigmentosa.

The U4 small nuclear RNA (snRNA) forms a duplex with the U6 snRNA and, together with U5 and ~30 proteins, is part of the U4/U6.U5 tri-snRNP complex, located at the core of the major spliceosome. Recently, recurrent variants in the U4 RNA, transcribed from the gene, and in at least two other genes were discovered to cause neurodevelopmental disorder.

The phenotypic spectrum of gene variants.

Introduction: Classically, Usher syndrome is characterized by the association of sensorineural hearing loss (SNHL), retinitis pigmentosa (RP) and possible vestibular dysfunction. Pathogenic bi-allelic variants in cause atypical autosomal recessive Usher syndrome, which is associated with SNHL and photoreceptors dysfunction without vestibular signs. To date, only 19 scattered descriptions have been reported.

Extensive macular atrophy with pseudodrusen-like appearance (EMAP) clinical characteristics, diagnostic criteria, and insights from allied inherited retinal diseases and age-related macular degeneration.

Extensive macular atrophy with pseudodrusen-like appearance (EMAP) was first described in France in 2009 as a symmetric and rapidly progressive form of macular atrophy primarily affecting middle-aged individuals. Despite the recent identification of a significant number of cases in Italy and worldwide, EMAP remains an underrecognized condition. The clinical triad typical of EMAP consists of vertically oriented macular atrophy with multilobular borders, pseudodrusen-like deposits across the posterior pole and mid-periphery, and peripheral pavingstone degeneration.

XOLARIS: A 24-Month, Prospective, Natural History Study of 201 Participants with -Associated X-Linked Retinitis Pigmentosa.

Objective: To improve the understanding of the natural disease progression of ()associated X-linked retinitis pigmentosa (XLRP).

Design: A multicenter, prospective, observational natural history study over 24 months.

Participants: Male participants aged ≥7 years with a pathogenic variant in the gene, a best-corrected visual acuity (BCVA) score of ≥34 ETDRS letters, and a mean 68-loci retinal sensitivity (assessed by microperimetry) of 0.

Differential pathogenetic mechanisms of mutations in helix 2 and helix 6 of rhodopsin.

Variants in rhodopsin (RHO) have been linked to autosomal dominant congenital stationary night blindness (adCSNB), which affects the ability to see in dim light, and the pathogenetic mechanism is still not well understood. In this study we report two novel RHO variants found in adCSNB families, p.W265R and p.

Novel and Recurrent Copy Number Variants in -Associated Retinopathy.

is the most frequently mutated gene leading to inherited retinal disease (IRD) with over 2200 pathogenic variants reported to date. Of these, ~1% are copy number variants (CNVs) involving the deletion or duplication of genomic regions, typically >50 nucleotides in length. An in-depth assessment of the current literature based on the public database LOVD, regarding the presence of known CNVs and structural variants in , and additional sequencing analysis of using single-molecule Molecular Inversion Probes (smMIPs) for 148 probands highlighted recurrent and novel CNVs associated with -associated retinopathies.

A Prospective, Observational, Non-interventional Clinical Study of Participants With Choroideremia: The NIGHT Study.

Purpose: The NIGHT study aimed to assess the natural history of choroideremia (CHM), an X-linked inherited chorioretinal degenerative disease leading to blindness, and determine which outcomes would be the most sensitive for monitoring disease progression.

Design: A prospective, observational, multicenter cohort study.

Methods: Males aged ≥18 years with genetically confirmed CHM, visible active disease within the macular region, and best-corrected visual acuity (BCVA) ≥34 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline were assessed for 20 months.

TBC1D32 variants disrupt retinal ciliogenesis and cause retinitis pigmentosa.

Retinitis pigmentosa (RP) is the most common inherited retinal disease (IRD) and is characterized by photoreceptor degeneration and progressive vision loss. We report 4 patients presenting with RP from 3 unrelated families with variants in TBC1D32, which to date has never been associated with an IRD. To validate TBC1D32 as a putative RP causative gene, we combined Xenopus in vivo approaches and human induced pluripotent stem cell-derived (iPSC-derived) retinal models.

variants causing retinitis pigmentosa or Usher syndrome provoke differential retinal phenotypes in disease-specific organoids.

There is an emblematic clinical and genetic heterogeneity associated with inherited retinal diseases (IRDs). The most common form is retinitis pigmentosa (RP), a rod-cone dystrophy caused by pathogenic variants in over 80 different genes. Further complexifying diagnosis, different variants in individual RP genes can also alter the clinical phenotype.

Mutational Spectrum, Ocular and Olfactory Phenotypes of -Related RP-Olfactory Dysfunction Syndrome in a Multiethnic Cohort.

gene mutations are a well-known cause of autosomal recessive retinitis pigmentosa (RP), which was recently associated with olfactory dysfunction. The purpose of this study was to report the molecular spectrum and the ocular and olfactory phenotypes of a multiethnic cohort with -associated RP. A cross-sectional case series was conducted at two ophthalmic genetics referral centers.