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Introduction: Bardet-Biedl Syndrome (BBS) is a ciliopathy causing developmental defects and progressive retinal dystrophy, whereas choroidal coloboma is a developmental defect causing structural deficiency in the posterior retina. Both are rarely reported together. Methods: Here, we describe the phenotype and genotype of three unrelated patients with co-occurrence of Bardet-Biedl Syndrome and chorioretinal coloboma and review the pertinent literature. Results: We describe three unrelated patients, with variable clinical features of Bardet Biedl syndrome. None had family history of BBS or coloboma. Each carried biallelic variants in BBS1, BBS9 and TTC8 gene, respectively. Two had unilateral chorioretinal coloboma, while one had bilateral chorioretinal coloboma. Discussion: Although there may be other explanatory factors yet to be revealed, our data suggests that chorioretinal coloboma may be associated with BBS. The Hedgehog (Hh) signaling pathway, an intercellular communicator for development of the eye, is dependent on the primary cilia and plays a crucial role in the closure of the optic fissure. Both disorders therefore involve disruption of primary cilia function which may explain their association. [ABSTRACT FROM AUTHOR]

Retinitis pigmentosa (RP) is the leading cause of heritable retinal visual impairment. Clinically, it is characterized by a variable onset of progressive night blindness and visual field constriction. RP is characterized by wide genetic heterogeneity with a broad range of potential genes involved in the genesis of this disease. Very few cases have been reported of RP due to pathogenic variants in AGBL5. We report two patients with RP and bilallelic pathogenic variants in AGBL5. Genetic sequencing showed one homozygous AGBL5 missense variant in one patient and a homozygous nonsense variant in the other. These patients presented with progressive peripheral vision loss and nyctalopia. Their RP phenotypes were similar to previous reports in literature. These two cases provide further evidence regarding the relationship of pathogenic variants in AGBL5 as a cause of autosomal recessive RP. [ABSTRACT FROM AUTHOR]

Retinitis pigmentosa (RP) is a major cause of blindness that affects 1.5 million people worldwide. Mutations in cyclic nucleotide-gated channel [beta] 1 (CNGB1) cause approximately 4% of autosomal recessive RP. Gene augmentation therapy shows promise for treating inherited retinal degenerations; however, relevant animal models and biomarkers of progression in patients with RP are needed to assess therapeutic outcomes. Here, we evaluated RP patients with CNGB1 mutations for potential biomarkers of progression and compared human phenotypes with those of mouse and dog models of the disease. Additionally, we used gene augmentation therapy in a CNG[beta]1-deficient dog model to evaluate potential translation to patients. CNGB1-deficient RP patients and mouse and dog models had a similar phenotype characterized by early loss of rod function and slow rod photoreceptor loss with a secondary decline in cone function. Advanced imaging showed promise for evaluating RP progression in human patients, and gene augmentation using adeno-associated virus vectors robustly sustained the rescue of rod function and preserved retinal structure in the dog model. Together, our results reveal an early loss of rod function in CNGB1-deficient patients and a wide window for therapeutic intervention. Moreover, the identification of potential biomarkers of outcome measures, availability of relevant animal models, and robust functional rescue from gene augmentation therapy support future work to move CNGB1-RP therapies toward clinical trials., Introduction Retinitis pigmentosa (RP) is a genetically heterogeneous cause of blindness, affecting approximately 1 in 4,000 individuals (1). Mutations for nonsyndromic RP have been identified in over 80 different genes [...]

Introduction: The etiologies of congenital and developmental cataracts are diverse. Most are not syndromic and have no identifiable cause, thus creating a diagnostic dilemma. We investigated the utility of chromosomal microarray in identifying the etiology of isolated childhood cataracts. Methods: Patients with congenital or developmental cataracts without other associated abnormalities received a single-nucleotide polymorphism (SNP) microarray. copy number variations (CNV) and regions of homozygosity (ROH) were compared with previous literature reports and analyzed for candidate genes to assess pathogenicity. Results: We enrolled 37 patients. The mean age of the patient population was 10.98 years old. Nineteen patients (51.4%) had bilateral cataract. Positive family history was found in 11 patients (29.7%). Eighteen patients (48.7%) had a variant on microarray: 10 (27%) with CNV, 5 (13.5%) with ROH, and 3 patients (8.1%) with both CNV and homozygosity. In five patients (13.5%), we found a potentially causative cataract gene within an ROH. Discussion: There is a high rate of notable findings among the CNV and ROH detected. Three patients were homozygous in a region known to have a cataract gene suggesting a possible autosomal recessive disease. In those with CNV, segregation would help to affirm the pathogenicity of these regions and may lead to the identification of new genes. Conclusion: SNP microarray had a surprisingly high rate of notable findings in patients with isolated cataract and may reveal the opportunities for genetic counseling, lead to discovering new cataract genes and identify additional affected genes that could lead to other clinical abnormalities. [ABSTRACT FROM AUTHOR]

Purpose: To report the occurrence of intraretinal cystoid spaces presumably due to retinal degeneration caused byCRB1mutations, and the response to treatment with carbonic anhydrase inhibitors. Materials: Retrospective case series. Methods: We report four patients with retinal degeneration and intraretinal cystoid spaces due toCRB1mutation. Of these patients, three were treated with topical carbonic anhydrase inhibitors. One of these three patients was changed to oral carbonic anhydrase inhibitor. Best corrected visual acuity and quantitative and qualitative macular optical coherence tomography results were recorded. Results: Three patients were compound heterozygous forCRB1mutations, and one had two mutations one of which was not found in the father. A total of seven different mutations were detected. All patients treated with carbonic anhydrase inhibitors experienced an improvement in visual acuity and decreased central retinal thickness, except in one eye in which retinal thickness paradoxically increased. Conclusions:CRB1mutations may be associated with intraretinal cystoid spaces. The use of carbonic anhydrase inhibitors can result in improved visual acuity in some patients. [ABSTRACT FROM AUTHOR]

Background: Leber congenital amaurosis (LCA) is most often an autosomal recessive disorder. We report a father and son with autosomal dominant LCA due to a mutation in the CRX gene. Materials and Methods: DNA screening using an allele specific assay of 90 of the most common LCA-causing variations in the coding sequences of AIPL1, CEP290, CRB1, CRX, GUCY2D, RDH12 and RPE65 was performed on the father. Automated DNA sequencing of his son examining exon 3 of the CRX gene was subsequently performed. Results: Both father and son have a heterozygous single base pair deletion of an adenine at codon 153 in the coding sequence of the CRX gene resulting in a frameshift mutation. Conclusion: Mutations involving the CRX gene may demonstrate an autosomal dominant inheritance pattern for LCA. [ABSTRACT FROM AUTHOR]

Organophosphates have rarely been reported to cause various ocular sequelae including retinal degeneration. Retinal manifestations have been rarely reported and poorly characterized. We describe a case of a 76-year-old man with vision loss beginning in his 20s due to acute on chronic exposure to dimethoate, an organophosphate. He presented with bilateral geographic macular atrophy and midperipheral pigmentary clumping which we characterized by dilated fundoscopic examination, optical coherence tomography, and fundus autofluorescence. [ABSTRACT FROM AUTHOR]

The cri-du-chat syndrome is a rare genetic disorder caused by deletions in the short arm of chromosome 5. It presents with a distinctive catlike high-pitched cry, psychomotor delays, microcephaly, craniofacial abnormalities, and, in many cases, ocular findings. We report the first child with cri-du-chat and the findings of unilateral corneal staphyloma due to Peters anomaly and retinal dysplasia., (Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Axenfeld-Rieger spectrum (ARS) includes the anterior segment abnormalities posterior embryotoxon, irido-corneal adhesions, corectopia, and other abnormalities of pupil size and shape. Glaucoma occurs in approximately 50% of affected children. It is often caused by mutations of FOXC1 or PITX2. Timing of expression and dosage of these transcription factors appear to be very critical in the development of the anterior segment. We report on one child with a deletion and another with a duplication involving 6p25, causing an anirdia-like phenotype. Classic anirdia is a pan-ophthalmic disorder caused by heterozygous mutations involving the paired homeobox gene PAX6 at 11p13. It is often associated with optic nerve hypoplasia, foveal hypoplasia, corneal pannus, nystagmus, and cataract. Microdeletion of 11p13 may be associated with life threatening Wilms tumor. Distinguishing these two syndromes has critical implications for prognosis and treatment. We demonstrate how chromosomal microarray can be instrumental in differentiating these phenotypes., (© 2015 Wiley Periodicals, Inc.)