Glaucoma Pred: Glaucoma prediction based on Myocilin genotype and phenotype information

Rangachari, K.; Bankoti, Namrata; Shyamala, N.; Michael, Daliah; Ahmed, Z. Sameer; Chandrasekaran, Prabha; Sekar, K.

doi:10.1016/j.ygeno.2018.04.006

Cited by 6 publications

(3 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compared with prior review articles (Cheng et al, 2012;Fingert et al, 2002;Gong et al, 2004;H. Wang et al, 2019) and databases (Hewitt et al, 2008;Rangachari et al, 2019) that focus on clinical or biochemical aspects of myocilin variants, we have taken a holistic approach: we consider available clinical metrics, related statistical analyses, as well as biological, cellular and biochemical behavior, and atomic-detail inferences from the OLF structure. We present the challenges in differentiating glaucoma variants from nondisease variants in this multifactorial disease and suggest paths forward to resolve ambiguities.…”

Section: Introductionmentioning

confidence: 99%

Common and rare myocilin variants: Predicting glaucoma pathogenicity based on genetics, clinical, and laboratory misfolding data

et al. 2021

View full text Add to dashboard Cite

Rare variants of the olfactomedin domain of myocilin are considered causative for inherited, early-onset open-angle glaucoma, with a misfolding toxic gain-of-function pathogenic mechanism detailed by 20 years of laboratory research. Myocilin variants are documented in the scientific literature and identified through large-scale genetic sequencing projects such as those curated in the Genome Aggregation Database (gnomAD). In the absence of key clinical and laboratory information, however, the pathogenicity of any given variant is not clear, because glaucoma is a heterogeneous and prevalent age-onset disease, and common variants are likely benign. In this review, we reevaluate the likelihood of pathogenicity for the~100 nonsynonymous missense, insertion-deletion, and premature termination of myocilin olfactomedin variants documented in the literature. We integrate available clinical, laboratory cellular, biochemical and biophysical data, the olfactomedin domain structure, and population genetics data from gnomAD. Of the variants inspected,~50% can be binned based on a preponderance of data, leaving many of uncertain pathogenicity that motivate additional studies. Ultimately, the approach of combining metrics from different disciplines will likely resolve outstanding complexities regarding the role of this misfolding-prone protein within the context of a multifactorial and prevalent ocular disease, and pave the way for new precision medicine therapeutics.

show abstract

Section: Introductionmentioning

confidence: 99%

Common and rare myocilin variants: Predicting glaucoma pathogenicity based on genetics, clinical, and laboratory misfolding data

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In a subset of patients, open-angle glaucoma is linked to genetic factors, namely, a mutation in the myocilin gene that is inherited in an autosomal dominant fashion and is characterized by frequent nucleotide substitutions [33,34]. A database on myocilin genotypes may help clinicians and researchers to identify individuals at risk of developing open-angle glaucoma [35].…”

Section: Ocular Adr To Gcsmentioning

confidence: 99%

Natural and iatrogenic ocular manifestations of rheumatoid arthritis: a systematic review

et al. 2021

View full text Add to dashboard Cite

Purpose To provide an overview of the ocular features of rheumatoid arthritis (RA) and of the ophthalmic adverse drug reactions (ADRs) that may be associated with the administration of antirheumatic drugs. Methods A systematic literature search was performed using the PubMed, MEDLINE, and EMBASE databases. In addition, a cohort of 489 RA patients who attended the Authors’ departments were examined. Results Keratoconjunctivitis sicca, episcleritis, scleritis, peripheral ulcerative keratitis (PUK), and anterior uveitis were diagnosed in 29%, 6%, 5%, 2%, and 10%, respectively, of the mentioned cohort. Ocular ADRs to non-steroidal anti-inflammatory drugs are rarely reported and include subconjunctival hemorrhages and hemorrhagic retinopathy. In patients taking indomethacin, whorl-like corneal deposits and pigmentary retinopathy have been observed. Glucocorticoids are frequently responsible for posterior subcapsular cataracts and open-angle glaucoma. Methotrexate, the prototype of disease-modifying antirheumatic drugs (DMARDs), has been associated with the onset of ischemic optic neuropathy, retinal cotton-wool spots, and orbital non-Hodgkin’s lymphoma. Mild cystoid macular edema and punctate keratitis in patients treated with leflunomide have been occasionally reported. The most frequently occurring ADR of hydroxychloroquine is vortex keratopathy, which may progress to “bull’s eye” maculopathy. Patients taking tofacitinib, a synthetic DMARD, more frequently suffer herpes zoster virus (HZV) reactivation, including ophthalmic HZ. Tumor necrosis factor inhibitors have been associated with the paradoxical onset or recurrence of uveitis or sarcoidosis, as well as optic neuritis, demyelinating optic neuropathy, chiasmopathy, and oculomotor palsy. Recurrent episodes of PUK, multiple cotton-wool spots, and retinal hemorrhages have occasionally been reported in patients given tocilizumab, that may also be associated with HZV reactivation, possibly involving the eye. Finally, rituximab, an anti-CD20 monoclonal antibody, has rarely been associated with necrotizing scleritis, macular edema, and visual impairment. Conclusion The level of evidence for most of the drug reactions described herein is restricted to the “likely” or “possible” rather than to the “certain” category. However, the lack of biomarkers indicative of the potential risk of ocular ADRs hinders their prevention and emphasizes the need for an accurate risk vs. benefit assessment of these therapies for each patient.

show abstract

“…at present, 771 nucleotide substitutions have been reported in the MYOC gene. among these, 331 substitutions are disease-causing mutations (dcM) (12). MYOC has been investigated for >20 years and is the most common mutated gene in patients with glaucoma (13,14).…”

Section: Introductionmentioning

confidence: 99%

Characterization of a novel mutation in the MYOC gene in a Chinese family with primary open‑angle glaucoma

et al. 2020

View full text Add to dashboard Cite

although primary open-angle glaucoma (PoaG)-related mutations in the myocilin (MYOC) gene have been reported, the underlying associations remain poorly understood. in the present study, the relationship between a MYOC mutation and PoaG was investigated using ophthalmic examination and total exon gene sequencing in a chinese family comprised of 5 individuals with PoaG and 15 unaffected individuals. Pathogenic mutations underlying PoaG were identified by whole-exome sequencing and subsequently validated by Sanger sequencing. of the family members, nine (45%) harbored heterozygous p.d208Y mutations; among these, five had POAG and four were unaffected. The mean age at diagnosis was 26.2±4.12 years and the mean intraocular pressure (ioP) was 39.7±16.58 mmHg; all affected members complained of vision loss, headaches and eye swelling. Among the five cases of PoaG, two presented with blindness. among 10 members of the family who underwent comprehensive ophthalmologic examination, 3 individuals exhibited severe visual field defects. The mean age at the time of operation was 27.2±3.54 years. in the present study, a novel MYOC mutation (c.G622T: p.d208Y) was identified that was associated with severe visual impairment, high ioP and the need for frequent surgical interventions. Some carriers of the mutation were young and did not show signs of glaucoma. These individuals should be followed-up to firmly establish whether the mutated gene is pathogenic for PoaG.

show abstract

Glaucoma Pred: Glaucoma prediction based on Myocilin genotype and phenotype information

Cited by 6 publications

References 16 publications

Common and rare myocilin variants: Predicting glaucoma pathogenicity based on genetics, clinical, and laboratory misfolding data

Common and rare myocilin variants: Predicting glaucoma pathogenicity based on genetics, clinical, and laboratory misfolding data

Natural and iatrogenic ocular manifestations of rheumatoid arthritis: a systematic review

Characterization of a novel mutation in the MYOC gene in a Chinese family with primary open‑angle glaucoma

Contact Info

Product

Resources

About