Clinical, Genetic, and Histopathological Characteristics of CRX-associated Retinal Dystrophies.

Purpose: To describe phenotypic, genotypic, and histopathological features of inherited retinal dystrophies associated with the CRX gene (CRX-RDs).

Design: Retrospective multicenter cohort study including histopathology.

Subjects: Thirty-nine patients from 31 families with pathogenic variants in the CRX gene.

Utilization of automated cilia analysis to characterize novel INPP5E variants in patients with non-syndromic retinitis pigmentosa.

INPP5E encodes inositol polyphosphate-5-phosphatase E, an enzyme involved in regulating the phosphatidylinositol (PIP) makeup of the primary cilium membrane. Pathogenic variants in INPP5E hence cause a variety of ciliopathies: genetic disorders caused by dysfunctional cilia. While the majority of these disorders are syndromic, such as the neuronal ciliopathy Joubert syndrome, in some cases patients will present with an isolated phenotype-most commonly non-syndromic retinitis pigmentosa (RP).

GNB1 and obesity: Evidence for a correlation between haploinsufficiency and syndromic obesity.

Most patients with GNB1 encephalopathy have developmental delay and/or intellectual disability, brain anomalies and seizures. Recently, two cases with GNB1 encephalopathy caused by haploinsufficiency have been reported that also show a Prader-Willi-like phenotype of childhood hypotonia and severe obesity. Here we present three new cases from our expert centre for genetic obesity in which GNB1 truncating and splice variants, probably leading to haploinsufficiency, were identified.

Efficacy of Carbonic Anhydrase Inhibitors on Cystoid Fluid Collections and Visual Acuity in Patients with X-Linked Retinoschisis.

Purpose: To date, there is no standard treatment regimen for carbonic anhydrase inhibitors (CAIs) in X-linked retinoschisis (XLRS) patients. This retrospective study aims to evaluate the efficacy of CAIs on visual acuity and cystoid fluid collections (CFC) in XRLS patients in Dutch and Belgian tertiary referral centers.

Design: Retrospective cohort study.

The Natural History of Leber Congenital Amaurosis and Cone-Rod Dystrophy Associated with Variants in the GUCY2D Gene.

Objective: To describe the spectrum of Leber congenital amaurosis (LCA) and cone-rod dystrophy (CORD) associated with the GUCY2D gene and to identify potential end points and optimal patient selection for future therapeutic trials.

Design: International, multicenter, retrospective cohort study.

Subjects: Eighty-two patients with GUCY2D-associated LCA or CORD from 54 families.

The Phenotypic and Mutational Spectrum of the FHONDA Syndrome and Oculocutaneous Albinism: Similarities and Differences.

Purpose: The purpose of this study was to further expand the mutational spectrum of the Foveal Hypoplasia, Optic Nerve Decussation defect, and Anterior segment abnormalities (FHONDA syndrome), to describe the phenotypic spectrum, and to compare it to albinism.

Subjects And Methods: We retrospectively collected molecular, ophthalmic, and electrophysiological data of 28 patients molecularly confirmed with FHONDA from the Netherlands (9), Israel (13), France (2), and the United States of America (4). We compared the data to that of 133 Dutch patients with the 3 most common types of albinism in the Netherlands: oculocutaneous albinism type 1 (49), type 2 (41), and ocular albinism (43).

X-Linked Retinoschisis: Novel Clinical Observations and Genetic Spectrum in 340 Patients.

Purpose: To describe the natural course, phenotype, and genotype of patients with X-linked retinoschisis (XLRS).

Design: Retrospective cohort study.

Participants: Three hundred forty patients with XLRS from 178 presumably unrelated families.

The Phenotypic Spectrum of Patients with PHARC Syndrome Due to Variants in : An Ophthalmic Perspective.

This study investigated the phenotypic spectrum of PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa and early-onset cataract) syndrome caused by biallelic variants in the gene. A total of 15 patients from 12 different families were included, with a mean age of 36.7 years (standard deviation [SD] ± 11.

Genotype-phenotype correlation in pseudoxanthoma elasticum.

Background And Aims: Pseudoxanthoma elasticum (PXE) is caused by variants in the ABCC6 gene. It results in calcification in the skin, peripheral arteries and the eyes, but has considerable phenotypic variability. We investigated the association between the ABCC6 genotype and calcification and clinical phenotypes in these different organs.

CLINICAL CHARACTERISTICS AND NATURAL HISTORY OF RHO-ASSOCIATED RETINITIS PIGMENTOSA: A Long-Term Follow-Up Study.

Purpose: To investigate the natural history of RHO-associated retinitis pigmentosa (RP).

Methods: A multicenter, medical chart review of 100 patients with autosomal dominant RHO-associated RP.

Results: Based on visual fields, time-to-event analysis revealed median ages of 52 and 79 years to reach low vision (central visual field <20°) and blindness (central visual field <10°), respectively.

-Associated Dystrophies: Clinical, Genetic, and Histopathological Features.

This study describes the clinical, genetic, and histopathological features in patients with -associated retinal dystrophies. Nine male patients from eight unrelated families underwent a comprehensive ophthalmic examination. Additionally, the histopathology of the right eye from a patient with an end-stage cone-rod-dystrophy (CRD)/sector retinitis pigmentosa (RP) phenotype was examined.

Long-Term Follow-Up of Retinal Degenerations Associated With Mutations and Their Comparability to Phenotypes Associated With Mutations.

Purpose: To investigate the natural history in patients with -associated retinal degenerations (RDs), in the advent of clinical trials testing treatment options.

Methods: A retrospective cohort of 13 patients with -RDs.

Results: Twelve patients from a genetic isolate carried a homozygous c.

The Spectrum of Structural and Functional Abnormalities in Female Carriers of Pathogenic Variants in the RPGR Gene.

Purpose: The purpose of this study was to investigate the phenotype and long-term clinical course of female carriers of RPGR mutations.

Methods: This was a retrospective cohort study of 125 heterozygous RPGR mutation carriers from 49 families.

Results: Eighty-three heterozygotes were from retinitis pigmentosa (RP) pedigrees, 37 were from cone-/cone-rod dystrophy (COD/CORD) pedigrees, and 5 heterozygotes were from pedigrees with mixed RP/CORD or unknown diagnosis.

The Phenotypic Spectrum of Albinism.

Purpose: To describe the phenotypic spectrum of a large cohort of albino patients, to investigate the relationship between the ocular abnormalities and the visual acuity (VA), and to define diagnostic criteria for the white population. We also estimated the prevalence of albinism in The Netherlands.

Design: Retrospective cohort study.

CLINICAL AND GENETIC CHARACTERISTICS OF MALE PATIENTS WITH RPGR-ASSOCIATED RETINAL DYSTROPHIES: A Long-Term Follow-up Study.

Purpose: To describe the phenotype and clinical course of patients with RPGR-associated retinal dystrophies, and to identify genotype-phenotype correlations.

Methods: A multicenter medical records review of 74 male patients with RPGR-associated retinal dystrophies.

Results: Patients had retinitis pigmentosa (RP; n = 52; 70%), cone dystrophy (COD; n = 5; 7%), or cone-rod dystrophy (CORD; n = 17; 23%).

LONG-TERM FOLLOW-UP OF PATIENTS WITH CHOROIDEREMIA WITH SCLERAL PITS AND TUNNELS AS A NOVEL OBSERVATION.

Purpose: To evaluate the long-term clinical course and visual outcome of patients with choroideremia.

Methods: Clinical examination, a social questionnaire, and medical records review of 21 patients with choroideremia from 14 families.

Results: The mean follow-up time was 25.

Genotypic and Phenotypic Characteristics of CRB1-Associated Retinal Dystrophies: A Long-Term Follow-up Study.

Purpose: To describe the phenotype, long-term clinical course, clinical variability, and genotype of patients with CRB1-associated retinal dystrophies.

Design: Retrospective cohort study.

Participants: Fifty-five patients with CRB1-associated retinal dystrophies from 16 families.

LONG-TERM FOLLOW-UP OF PATIENTS WITH RETINITIS PIGMENTOSA TYPE 12 CAUSED BY CRB1 MUTATIONS: A Severe Phenotype With Considerable Interindividual Variability.

Purpose: To examine the long-term clinical course and variability in a large pedigree segregating CRB1 type autosomal recessive retinitis pigmentosa.

Methods: An observational case study of 30 patients with CRB1 type autosomal recessive retinitis pigmentosa, homozygous for the CRB1 c.3122T > C; p.

Retinitis pigmentosa, cutis laxa, and pseudoxanthoma elasticum-like skin manifestations associated with GGCX mutations.

Gamma-glutamyl carboxylase (GGCX) mutations have been reported in patients with a pseudoxanthoma elasticum (PXE)-like phenotype, loose redundant skin, and multiple vitamin K-dependent coagulation factor deficiencies. We report on the clinical findings and molecular results in 13 affected members of two families who had a uniform phenotype consisting of (PXE)-like skin manifestations in the neck and trunk, loose sagging skin of the trunk and upper limbs, and retinitis pigmentosa confirmed by electroretinographies in 10 affected individuals. There were no coagulation abnormalities.

Ultrastructural localization of GPR179 and the impact of mutant forms on retinal function in CSNB1 patients and a mouse model.

Purpose: Complete congenital stationary night blindness (CSNB1) is characterized by loss of night vision due to a defect in the retinal ON-bipolar cells (BCs). Mutations in GPR179, encoding the G-protein-coupled receptor 179, have been found in CSNB1 patients. In the mouse, GPR179 is localized to the tips of ON-BC dendrites.

Genotype and phenotype of 101 dutch patients with congenital stationary night blindness.

Objective: To investigate the relative frequency of the genetic causes of the Schubert-Bornschein type of congenital stationary night blindness (CSNB) and to determine the genotype-phenotype correlations in CSNB1 and CSNB2.

Design: Clinic-based, longitudinal, multicenter study.

Participants: A total of 39 patients with CSNB1 from 29 families and 62 patients with CSNB2 from 43 families.

Autosomal recessive bestrophinopathy: differential diagnosis and treatment options.

Objective: To describe the clinical and genetic characteristics of patients with autosomal recessive bestrophinopathy (ARB).

Design: Retrospective case series.

Participants: Ten patients with ARB from 7 different families.