Phosphoribosyl pyrophosphate synthetase 1 () associated retinal degeneration: an international study.

Introduction: Phosphoribosyl pyrophosphate synthetase 1 () is an X-linked gene critical for nucleotide metabolism. Pathogenic variants cause three overlapping phenotypes: Arts syndrome (severe neurological disease), Charcot-Marie-Tooth type 5 [CMTX5] (peripheral neuropathy), and non-syndromic sensorineural hearing loss (SNHL). Each may be associated with retinal dystrophy.

A Comprehensive Report of Intrinsically Disordered Regions in Inherited Retinal Diseases.

Background/purpose: A comprehensive review of the degree of disorder in all genes in the Retinal Information Network (RetNet) Database is implicated in inherited retinal diseases (IRDs). Their association with a missense variation was evaluated.

Methods: IRD genes from RetNet were included in this study.

Expanding the phenotypic and genotypic spectrum of patients with -related retinopathy.

Background: Variants in HGSNAT have historically been associated with syndromic mucopolysaccharidosis type IIIC (MPSIIIC) but more recent studies demonstrate cases of HGSNAT-related non-syndromic retinitis pigmentosa. We describe and expand the genotypic and phenotypic spectrum of this disease.

Materials And Methods: This is a retrospective, observational, case series of 11 patients with pericentral retinitis pigmentosa due to variants in HGSNAT gene without a syndromic diagnosis of MPSIIIC.

Molecular and Clinical Characterization of and Genes in Brazilian Patients Affected with Achromatopsia.

Achromatopsia (ACHM) is a congenital cone photoreceptor disorder characterized by reduced visual acuity, nystagmus, photophobia, and very poor or absent color vision. Pathogenic variants in six genes encoding proteins composing the cone phototransduction cascade (, , , , ) and of the unfolded protein response () have been related to ACHM cases, while and alone are responsible for most cases. Herein, we provide a clinical and molecular overview of 42 Brazilian patients from 38 families affected with ACHM related to biallelic pathogenic variants in the and genes.

Improved Rod Sensitivity as Assessed by Two-Color Dark-Adapted Perimetry in Patients With RPE65-Related Retinopathy Treated With Voretigene Neparvovec-rzyl.

Purpose: The purpose of this study was to evaluate rod-mediated function with two-color dark-adapted perimetry (2cDAP) in patients with RPE65-related retinopathy treated with voretigene neparvovec-rzyl.

Methods: Following dilation and dark adaptation, 2cDAP and FST were performed. The 2cDAP was measured on an Octopus 900 perimeter (Haag-Streit) with cyan (500 nm wavelength) and red (650 nm wavelength) stimuli.

A patient with X-linked retinoschisis and exudative retinal detachment associated with a pathogenic hemizygous variant c.304c>T in .

Background: X-linked retinoschisis (XLRS) is a rare retinal dystrophy due to pathogenic variants in the RS1 gene. The hallmark of the disease is a foveal spoke-wheel appearance. The purpose of this report is to expand the phenotypic spectrum of XLRS reporting a patient with atypical phenotype of XLRS associated with Coats-like phenotype.

A DOUBLE HYPERAUTOFLUORESCENT RING IN A 33-YEAR-OLD-FEMALE PATIENT.

Purpose: To describe the clinical phenotype and molecular diagnosis of a patient with atypical presentation of enhanced S-cone syndrome.

Methods: This is a case report of a patient who underwent best-corrected visual acuity, slit-lamp exam, fundus examination, autofluorescence, optical coherence tomography, kinetic perimetry, and full-field electroretinography. Genetic testing was performed via next-generation sequencing.

Three-Year Safety Results of SAR422459 (EIAV-ABCA4) Gene Therapy in Patients With ABCA4-Associated Stargardt Disease: An Open-Label Dose-Escalation Phase I/IIa Clinical Trial, Cohorts 1-5.

Purpose: To report on the safety of the first 5 cohorts of a gene therapy trial using recombinant equine infectious anemia virus expressing ABCA4 (EIAV-ABCA4) in adults with Stargardt dystrophy due to mutations in ABCA4.

Design: Nonrandomized multicenter phase I/IIa clinical trial.

Methods: Patients received a subretinal injection of EIAVABCA4 in the worse-seeing eye at 3 dose levels and were followed for 3 years after treatment.

Effect of Pharmacological Pupil Dilation on Dark-Adapted Perimetric Sensitivity in Healthy Subjects Using an Octopus 900 Perimeter.

Purpose: To determine whether dilation status has a clinically meaningful effect on sensitivity in normal subjects undergoing two-color dark-adapted perimetry, which can be useful to assess rod function.

Methods: A perimeter measured naturally and pharmacologically dilated scotopic sensitivities using a test grid consisting of 16 points across the horizontal meridian ranging from 60° temporal to 45° nasal using cyan (500 nm wavelength) or red (650 nm wavelength) stimuli. The primary outcome was average overall sensitivity based on dilation status, which was compared using a linear mixed effect model for each color stimuli.

Variable expressivity of -associated autosomal dominant vitreoretinochoroidopathy (ADVIRC) in a three-generation pedigree.

Objective: Autosomal dominant vitreoretinochoroidopathy (ADVIRC) is associated with pathogenic variants in , which typically causes visual impairment in the late stage of disease. We present a pedigree with variable expressivity and the youngest case in the literature with visual impairment in early childhood.

Methods And Analysis: This is a retrospective, observational, case series describing multigenerational members of one family affected with ADVIRC.

Expanding the clinical phenotype in patients with disease causing variants associated with atypical Usher syndrome.

Atypical Usher syndrome (USH) is poorly defined with a broad clinical spectrum. Here, we characterize the clinical phenotype of disease caused by variants in , and .Chart review evaluating demographic, clinical, imaging, and genetic findings of 19 patients from 18 families with a clinical diagnosis of retinal disease and confirmed disease-causing variants in , or .

Characterization of the Spectrum of Ophthalmic Changes in Patients With Alagille Syndrome.

Purpose: The purpose of this study was to characterize the phenotypic spectrum of ophthalmic findings in patients with Alagille syndrome.

Methods: We conducted a retrospective, observational, multicenter, study on 46 eyes of 23 subjects with Alagille syndrome. We reviewed systemic and ophthalmologic data extracted from medical records, color fundus photography, fundus autofluorescence, optical coherence tomography, visual fields, electrophysiological assessments, and molecular genetic findings.

Expanding the Phenotypic and Genotypic Spectrum of Bietti Crystalline Dystrophy.

The rare form of retinal dystrophy, Bietti crystalline dystrophy, is associated with variations in , a member of the cytochrome P450 family. This study reports patients affected by typical and atypical Bietti crystalline dystrophy, expanding the spectrum of this disease. This is an observational case series of patients with a clinical and molecular diagnosis of Bietti crystalline dystrophy that underwent multimodal imaging.

- associated microcephaly and chorioretinopathy.

Microcephaly and chorioretinopathy (MCCRP) is a rare neuro-ophthalmologic disorder that causes microcephaly and chorioretinopathy. In a recessive inheritance pattern, there are three types: MCCRP1; MCCRP2 and MCCRP3. MCCRP3 results from pathogenic variants in the ( gene.

Synonymous Variant in the CHM Gene Causes Aberrant Splicing in Choroideremia.

Purpose: Choroideremia is an inherited retinal degeneration caused by 280 different pathogenic variants in the CHM gene. Only one silent/synonymous variant (c.1359C>T; p.