Ophthalmic Genetics

PURPOSE: To assess age at 1st central retinal vein occlusion (CRVO) in carriers ≤ 45 years old of the methylenetetrahydrofolate reductase (MTHFR) C667T genotype compared to heterozygous and wild type, and to identify predictors of age at CRVO. METHODS: Retrospective cohort study consisting of 18 MTHFR TT, 23 MTHFR TC and 28 MTHFR CC participants; information regarding age, sex, age at CRVO, history of dyslipidaemia, hypertension, smoking and plasma HC measured by immunoassay were collected...

PURPOSE: This study aims to evaluate the ABCA4 variants in patients diagnosed with Stargardt disease. METHODS: This is a retrospective study designed to investigate variants in the ABCA4 in Stargardt disease and the clinical findings of the cases. Sex, age, age of onset of symptoms, best-corrected visual acuity, color fundus photography, optical coherence tomography, and visual field test of the patients were recorded. Genetic analyses were screened, and patients with at least two variants in the ABCA4 were included in this study...

No abstract text is available yet for this article.

INTRODUCTION: Biotinidase deficiency (BD) is an inherited autosomal recessive metabolic disorder. BD has been associated with optic nerve atrophy, eye infections, and retinopathy. The most prevalent ophthalmic manifestation of BD is optic atrophy, which might be misdiagnosed as multiple sclerosis or neuromyelitis optica, especially in late-onset BD cases. METHODS: In this article, we report a 9-year-old boy with gradual vision loss. Ophthalmologic examination, Brain MRI, and several laboratory tests such as Aquaporin-4 IgG level and biotinidase level were done on the patient...

INTRODUCTION: Mutations in the retinal pigment epithelial 65 kilodalton protein ( RPE65 ) gene are associated with various inherited retinal diseases (IRDs), including Leber congenital amaurosis (LCA), early-onset severe retinal dystrophy (EOSRD), and retinitis pigmentosa (RP). We screened for mutations in RPE65 in a series of Indian patients with these IRDs to determine the frequency/types of mutations and to describe the associated phenotypes. MATERIALS AND METHODS: Diagnosis of LCA, EOSRD, and RP was made by standard and pre-defined criteria...

BACKGROUND: Stickler syndrome (STL) is a collagenopathy caused by pathogenic variants in collagen-coding genes, mainly COL2A1 or COL11A1 associated with Stickler syndrome type 1 (STL1) or type 2 (STL2), respectively. Affected individuals manifest ocular, auditory, articular, and craniofacial findings in varying degrees. Previous literature and case reports describe high variability in clinical findings for patients with STL. With this case report, we broaden the clinical spectrum of the phenotype...

BACKGROUND: Variations in ZNF469 have been associated with Brittle Cornea Syndrome that presents with bluish sclera, loss of vision after trivial trauma, arachnodactyly, and joint laxity. MATERIALS AND METHODS: Detailed medical and family history, physical examination, and molecular analysis. RESULTS: A 21-year-old female presented with bluish discoloration of sclera, diminution of vision following trivial trauma in childhood along with hearing loss and systemic features of arachnodactyly and joint laxity...

OBJECTIVE: To develop an updated staging system for long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency (LCHADD) chorioretinopathy based on contemporary multimodal imaging and electrophysiology. METHODS: We evaluated forty cases of patients with genetically confirmed LCHADD or trifunctional protein deficiency (TFPD) enrolled in a prospective natural history study. Wide-field fundus photographs, fundus autofluorescence (FAF), optical coherence tomography (OCT), and full-field electroretinogram (ffERG) were reviewed and graded for severity...

PURPOSE: To identify RHO mutations in patients with non-syndromic retinitis pigmentosa (NS-RP). METHODS: A total of 143 probands (46 family history and 97 sporadic cases) with NS-RP were recruited from Southeast China. The coding exons and adjacent intronic regions of RHO were PCR-amplified and sequenced by Sanger sequencing. The candidate variant was evaluated by the guidelines of American College of Medical Genetics and further validated through co-segregation analysis within the family...

INTRODUCTION: Molecular confirmation of pathogenic sequence variants in the CHM gene is required prior to enrolment in retinal gene therapy clinical trials for choroideremia. Individuals with mild choroideremia have been reported. The molecular basis of genotype-phenotype associations is of clinical relevance since it may impact on selection for retinal gene therapy. METHODS AND MATERIALS: Genetic testing and RNA analysis were undertaken in a patient with mild choroideremia to confirm the pathogenicity of a novel intronic variant in CHM and to explore the mechanism underlying the mild clinical phenotype...

BACKGROUND: Biallelic variants in RTN4IP1 are a well-established cause of syndromic and nonsyndromic early-onset autosomal recessive optic neuropathy. They have more recently been reported to cause a concomitant but later-onset rod-cone dystrophy with or without syndromic features. METHODS: A comprehensive evaluation was performed that included assessment of visual and retinal function, clinical examination, and retinal imaging. Childhood ophthalmic records as well as the results of genetic testing were evaluated...

BACKGROUND: We report a three-generation family with isolated Alport-like retinal abnormalities in the absence of lenticonus, hearing loss, kidney disease, and detectable molecular genetic defects in known Alport-related genes. METHODS: Clinical examination includes ocular biomicroscopy, fundus photography, optical coherence tomography, dipstick urinalysis, serum creatinine assessment, and molecular genetic analysis. RESULTS: The proband, her mother, and her maternal grandmother had normal best-corrected visual acuity and normal visual fields in both eyes...

BACKGROUND: PHARC syndrome (MIM:612674) is a rare neurodegenerative disorder characterized by demyelinating polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataracts (PHARC). The syndrome is caused by mutations in the ABHD12 gene, which encodes αβ-hydrolase domain-containing protein 12 related to endocannabinoid metabolism. PHARC syndrome is one of the rare diseases; so far, only 51 patients have been reported in the literature. METHODS: We evaluated the 25-year-old male patient referred to us due to vision loss, cataracts, and hearing loss...

BACKGROUND: The aim of this study is to determine the association of TAS2R16 (rs860170, rs978739, rs1357949) gene polymorphisms and TAS2R16 serum levels in patients with the occurrence of age-related macular degeneration (AMD). METHODS: Subjects with early AMD, subjects with exudative AMD, and healthy controls participated in the study. DNA was isolated by salting out leukocytes from peripheral venous blood. Single nucleotide polymorphisms (SNPs) were analysed by RT-PCR...

INTRODUCTION: Schimmelpenning-Feurstein-Mims Syndrome (SFMS) is a rare neurocutaneous disorder. Herein, we describe a novel case and review the phenotypic spectrum and molecular findings of SFMS from an ophthalmology perspective. METHODS: Clinical case including presentation, management, pathology, and genetic analysis is described. A literature search on Schimmelpenning-Feuerstein-Mims and its synonyms, Linear nevus sebaceous syndrome, Organoid nevus syndrome, Jadassohn nevus phacomatosis, and Solomon syndrome, was conducted...

PURPOSE: We report a case of Hermansky-Pudlak Syndrome type 7 (HPS-7) caused by a homozygous variant in the dystrobrevin-binding protein 1 gene ( DTNBP1 ) and highlight the genetic challenges associated with this rare disorder. METHODS: Case report. Literature review was performed by searching PubMed on May 2023, without language or date restriction, using the following terms: Hermansky-Pudlak syndrome, Hermansky-Pudlak syndrome type 7, and dystrobrevin-binding protein 1 gene...

BACKGROUND: In 2020, a new disease was reported by Polovitskaya et al., caused by a monoallelic, gain-of-function mutation in CLCN6 , encoding the ClC-6 Cl-/H±exchanger. METHODS: Here, we report the ophthalmic findings of one of the first three patients with this disease (the proband) and review the findings in the other two patients in the literature. RESULTS: The CLCN6 gene is part of the voltage-dependent chloride channel protein family...

BACKGROUND: 48, XXYY syndrome is a rare sex chromosome aneuploidy with severe systemic features. Ophthalmic manifestation of 48, XXYY syndrome include hypertelorism, epicanthic folds, hooded eye lids, strabismus, retinitis pigmentosa and Duane's syndrome. CASE: We present mild foveal hypoplasia in a 12-year-old boy with 48, XXYY syndrome using swept-source optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). The boy was referred for assessment of strabismus and poor visual acuity...

BACKGROUND: Pathogenic variants in IFT140 have been reported in cases of both syndromic and nonsyndromic retinitis pigmentosa (RP). Syndromic forms of IFT140 -related RP have been associated with short-rib thoracic dysplasia. IFT140 variants have also been shown to cause spermatogenic dysfunction leading to infertility. However, variants in IFT140 have not been reported in patients with concurrent RP (including nonsyndromic RP) and infertility. METHODS: A chart review was performed in a 42 year old male with RP and male factor infertility...

BACKGROUND: 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 . MATERIALS AND METHODS: We report two patients with RP and bilallelic pathogenic variants in AGBL5 ...