The Clinical and Mutational Spectrum of Bardet-Biedl Syndrome in Saudi Arabia.

The retinal features of Bardet-Biedl syndrome (BBS) are insufficiently characterized in Arab populations. This retrospective study investigated the retinal features and genotypes of BBS in Saudi patients managed at a single tertiary eye care center. Data analysis of the identified 46 individuals from 31 families included visual acuity (VA), systemic manifestations, multimodal retinal imaging, electroretinography (ERG), family pedigrees, and genotypes.

Enhanced Learning and Memory in Patients with Retinopathy.

Unlabelled: Mutations in the gene are associated with a diverse spectrum of retinopathies with phenotypic variability causing severe visual impairment. The gene has a role in retinal development and is expressed in the cerebral cortex and hippocampus, but its role in cognition has not been described before. This study compares cognitive function in retinopathy individuals with subjects with other retinopathies and the normal population.

-associated retinopathy: a diagnostic odyssey.

Purpose: This study describes how the diagnosis of Usher syndrome was revised to PRPS1-associated retinopathy and Charcot-Marie-Tooth disease type 5.

Case Report: A 38-year-old female with bilaterally subnormal vision and non-congenital hearing loss was initially diagnosed with Usher syndrome, based on finding variants in three genes (MYO7A, USH2A, and PCDH15), was re-evaluated at the inherited retinal disorders clinic. She had asymmetric retinopathy and right macular pseudocoloboma.

CERKL-Associated Retinal Dystrophy: Genetics, Phenotype, and Natural History.

Purpose: To analyze the clinical characteristics, natural history, and genetics of CERKL-associated retinal dystrophy in the largest series to date.

Design: Multicenter retrospective cohort study.

Subjects: Forty-seven patients (37 families) with likely disease-causing CERKL variants.

Phenotypic and genotypic features of -associated cone dystrophy.

Purpose: Patients with cone dystrophy (CD) can present with virtually normal retinal appearance, which may delay diagnosis. This study describes the inconspicuous clinical features of -associated CD in two Saudi families.

Methods: This is a retrospective case study.

Broadening INPP5E phenotypic spectrum: detection of rare variants in syndromic and non-syndromic IRD.

Pathogenic variants in INPP5E cause Joubert syndrome (JBTS), a ciliopathy with retinal involvement. However, despite sporadic cases in large cohort sequencing studies, a clear association with non-syndromic inherited retinal degenerations (IRDs) has not been made. We validate this association by reporting 16 non-syndromic IRD patients from ten families with bi-allelic mutations in INPP5E.

CNGB1-related rod-cone dystrophy: A mutation review and update.

Cyclic nucleotide-gated channel β1 (CNGB1) encodes the 240-kDa β subunit of the rod photoreceptor cyclic nucleotide-gated ion channel. Disease-causing sequence variants in CNGB1 lead to autosomal recessive rod-cone dystrophy/retinitis pigmentosa (RP). We herein present a comprehensive review and analysis of all previously reported CNGB1 sequence variants, and add 22 novel variants, thereby enlarging the spectrum to 84 variants in total, including 24 missense variants (two of which may also affect splicing), 21 nonsense, 19 splicing defects (7 at noncanonical positions), 10 small deletions, 1 small insertion, 1 small insertion-deletion, 7 small duplications, and 1 gross deletion.

Ceramide synthase TLCD3B is a novel gene associated with human recessive retinal dystrophy.

Purpose: Previous studies suggest that ceramide is a proapoptotic lipid as high levels of ceramides can lead to apoptosis of neuronal cells, including photoreceptors. However, no pathogenic variant in ceramide synthases has been identified in human patients and knockout of various ceramide synthases in mice has not led to photoreceptor degeneration.

Methods: Exome sequencing was used to identify candidate disease genes in patients with vision loss as confirmed by standard evaluation methods, including electroretinography (ERG) and optical coherence tomography.

Macula-predominant retinopathy associated with biallelic variants in .

Purpose: To describe the clinical, electrophysiological, and molecular features of an unusual macula-predominant retinopathy in two unrelated probands with biallelic variants in .

Methods: Retrospective case series.

Results: A 29-year-old female presented with visual loss since the age of 14 years.

A genetic and clinical study of individuals with nonsyndromic retinopathy consequent upon sequence variants in HGSNAT, the gene associated with Sanfilippo C mucopolysaccharidosis.

Pathogenic variants in the gene HGSNAT (heparan-α-glucosaminide N-acetyltransferase) have been reported to underlie two distinct recessive conditions, depending on the specific genotype, mucopolysaccharidosis type IIIC (MPSIIIC)-a severe childhood-onset lysosomal storage disorder, and adult-onset nonsyndromic retinitis pigmentosa (RP). Here we describe the largest cohort to-date of HGSNAT-associated nonsyndromic RP patients, and describe their retinal phenotype, leukocyte enzymatic activity, and likely pathogenic genotypes. We identified biallelic HGSNAT variants in 17 individuals (15 families) as the likely cause of their RP.

A clinical study of patients with novel CDHR1 genotypes associated with late-onset macular dystrophy.

Purpose: To describe the clinical and electrophysiological features of adult-onset macular dystrophy, due to novel combinations of CDHR1 alleles, and compare the associated phenotypes with previous reports.

Methods: The clinical records of patients with macular dystrophy and biallelic variants in CDHR1 were reviewed. Data analysed included best corrected visual acuity (BCVA), fundus images: autofluorescence (AF) and optical coherence tomography (OCT); full field electroretinography (ERG) and pattern ERG (PERG).

MONOZYGOTIC TWINS DISCORDANT FOR ASYMMETRIC PIGMENTED PARAVENOUS CHORIORETINAL ATROPHY.

Purpose: To demonstrate phenotypic discordance between a monozygotic twin pair, one of whom exhibited pigmented paravenous chorioretinal atrophy (PPCRA).

Methods: A patient and his identical twin brother, attending Moorfields Eye Hospital, were reviewed. Clinical assessment included visual acuity and color vision testing, fundus imaging including autofluorescence, spectral-domain optical coherence tomography, and static perimetry.

Genetic Basis of Inherited Retinal Disease in a Molecularly Characterized Cohort of More Than 3000 Families from the United Kingdom.

Purpose: In a large cohort of molecularly characterized inherited retinal disease (IRD) families, we investigated proportions with disease attributable to causative variants in each gene.

Design: Retrospective study of electronic patient records.

Participants: Patients and relatives managed in the Genetics Service of Moorfields Eye Hospital in whom a molecular diagnosis had been identified.

Macular maldevelopment in -mediated retinal dysfunction.

: Achromatopsia has been previously associated with mutations in the gene. Rod-monochromatism, foveal hypoplasia, and disruption of the subfoveal photoreceptor layer are described as phenotypical features. We report detailed structural and electrophysiological assessment of two patients from two families, one manifesting severe macular maldevelopment and one with foveal hypoplasia.

Reanalysis of Association of Pro50Leu Substitution in Guanylate Cyclase Activating Protein-1 With Dominant Retinal Dystrophy.

Importance: As genetic and genomic screening is becoming more widely accessed, correctly distinguishing pathogenic from nonpathogenic variants is of increasing relevance.

Objective: To reevaluate a previously reported family in whom the p.(Pro50Leu) variant in the gene GUCA1A was associated with a dominant retinal dystrophy, in light of new examination findings in the proband's daughter.

Isolated rod dysfunction associated with a novel genotype of .

Purpose: To describe the clinical and electrophysiological features of an unusual retinopathy in a patient with a novel genotype of , mutations in which are implicated in autosomal recessive retinitis pigmentosa (rod-cone dystrophy).

Observations: A 61-year old asymptomatic woman was referred to the inherited retinal disorders clinic because of peripheral retinal pigmentary changes. She had normal visual acuity and color vision.

Clinical Features of a Retinopathy Associated With a Dominant Allele of the RGR Gene.

Purpose: We describe the clinical features in two pedigrees with dominantly inherited retinopathy segregating the previously reported frameshifting mutation, c.836dupG (p.Ile280Asn*78) in the terminal exon of the RGR gene, and compare their haplotypes to that of the previously reported pedigree.

Retinal Architecture in ​RGS9- and ​R9AP-Associated Retinal Dysfunction (Bradyopsia).

Purpose: To characterize photoreceptor structure and mosaic integrity in subjects with ​RGS9- and R9AP-associated retinal dysfunction (bradyopsia) and compare to previous observations in other cone dysfunction disorders such as oligocone trichromacy.

Design: Observational case series.

Methods: setting: Moorfields Eye Hospital (United Kingdom) and Medical College Wisconsin (USA).

Prph2 mutations as a cause of electronegative ERG.

Purpose: To describe the phenotypic and genotypic features in patients with PRPH2 mutations and negative electroretinograms.

Methods: Retrospective observational case series. Records of patients with a confirmed molecular diagnosis of PRPH2 mutation, and an electronegative electroretinogram (reduced b-wave to a-wave amplitude ratio) under either photopic or scotopic conditions, were identified.

Clinical characteristics of early retinal disease due to CDHR1 mutation.

Purpose: To describe the early clinical and electrophysiological features of cone-rod dystrophy due to a mutation of cadherin-related family member 1 (CDHR1).

Methods: Three affected siblings from a consanguineous family were ascertained. The clinical data included retinal examination, Goldmann visual fields, fundus autofluorescence imaging, optical coherence tomography (OCT), and pattern and full-field electroretinograms.