Genetics in Keratoconus - What is New?
Ontology highlight
ABSTRACT:
SUBMITTER: Moussa S
PROVIDER: S-EPMC5585456 | biostudies-literature | 2017
REPOSITORIES: biostudies-literature
Publications
Genetics in Keratoconus - What is New?
Moussa Sarah S Grabner Günther G Ruckhofer Josef J Dietrich Marie M Reitsamer Herbert H
The open ophthalmology journal 20170731
<h4>Background</h4>Keratoconus is characterized as a bilateral, progressive, non-inflammatory thinning of the cornea resulting in blurred vision due to irregular astigmatism. Keratoconus has a multifactorial etiology, with multiple genetic and environmental components contributing to the disease pathophysiology. Several genomic loci and genes have been identified that highlight the complex molecular etiology of this disease.<h4>Conclusion</h4>The review focuses on current knowledge of these gene ...[more]
Similar Datasets
Project description:Keratoconus (KTCN) is non-inflammatory thinning and anterior protrusion of the cornea that results in steepening and distortion of the cornea, altered refractive error, and decreased vision. Keratoconus is a complex condition of multifactorial etiology. Both genetic and environmental factors are associated with KTCN. Evidence of genetic etiology includes familial inheritance, discordance between dizygotic twins, and association with other known genetic disorders. Several loci responsible for a familial form of KTCN have been mapped; however, no mutations in any genes have been identified for any of these loci. This article focuses on the genetic aspects. In addition, bioinformatics methods applied in KTCN gene identification process are discussed.
| S-EPMC3085147 | biostudies-literature
Project description:Keratoconus (KC) is a non-inflammatory thinning and protrusion of the cornea in which the cornea assumes a conical shape. Complex etiology of this condition at present remains an enigma. Although environmental factors have been involved in KC pathogenesis, strong underlining genetic susceptibility has been proven. The lack of consistent findings among early genetic studies suggested a heterogeneity and complex nature of the genetic contribution to the development of KC. Recently, genome-wide linkage studies (GWLS) and genome-wide association studies (GWAS) were undertaken. Next-generation sequencing (NGS)-based genomic screens are also currently being carried out. Application of these recently developed comprehensive genetic tools led to a much greater success and increased reproducibility of genetic findings in KC. Involvement of the LOX gene identified through GWLS has been confirmed in multiple cohorts of KC patients around the world. KC susceptibility region located at the 2q21.3 chromosomal region near the RAB3GAP1 gene identified through GWAS was independently replicated. Rare variants in the ZNF469 gene (mutated in corneal dystrophy Brittle Cornea Syndrome) and in the TGFBI gene (mutated in multiple corneal epithelial-stromal TGFBI dystrophies) have been repeatedly identified in familial and sporadic KC patients of different ethnicities. Additional comprehensive strategies using quantitative endophenotypes have been successfully employed to bring further understanding to the genetics of KC. Additional genetic determinants including the COL5A1 gene have been identified in the GWAS of KC-related trait central corneal thickness. These recent discoveries confirmed the importance of the endophenotype approach for studying complex genetic diseases such as KC and showed that different connective tissue disorders may have the same genetic determinants.
| S-EPMC4922054 | biostudies-literature
Project description:Keratoconus is the most common ectatic disorder of the corneal. Genetic and environmental factors may contribute to its pathogenesis. The focus of this article is to summarize current research into the complex genetics of keratoconus. We discuss the evidence of genetic etiology including family-based linkage studies, twin studies, genetic mutations, and genome-wide association studies. The genes implicated potentially include VSX1, miR-184, DOCK9, SOD1, RAB3GAP1, and HGF. Besides the coding mutations, we also highlight the potential contribution of DNA copy number variants in the pathogenesis of keratoconus. Finally, we present future directions for genetic research in the understanding of the complex genetics of keratoconus and its clinical significance. As new functional, candidate genes for keratoconus are being discovered at a rapid pace, the molecular genetic mechanisms underlying keratoconus pathogenesis will advance our understanding of keratoconus and promote the development of a novel therapy.
| S-EPMC3686480 | biostudies-literature
Project description:Keratoconus is a progressive thinning and anterior protrusion of the cornea that results in steepening and distortion of the cornea, altered refractive powers, and reduced vision. Keratoconus has a complex multifactorial etiology, with environmental, behavioral, and multiple genetic components contributing to the disease pathophysiology. Using genome-wide and candidate gene approaches several genomic loci and genes have been identified that highlight the complex molecular etiology of this disease. The review focuses on current knowledge of these genetic risk factors associated with keratoconus.
| S-EPMC4164130 | biostudies-literature
Project description:PurposeTo characterize corneal structural changes in keratoconus using a new morphogeometric approach and to evaluate its potential diagnostic ability.MethodsComparative study including 464 eyes of 464 patients (age, 16 and 72 years) divided into two groups: control group (143 healthy eyes) and keratoconus group (321 keratoconus eyes). Topographic information (Sirius, CSO, Italy) was processed with SolidWorks v2012 and a solid model representing the geometry of each cornea was generated. The following parameters were defined: anterior (Aant) and posterior (Apost) corneal surface areas, area of the cornea within the sagittal plane passing through the Z axis and the apex (Aapexant, Aapexpost) and minimum thickness points (Amctant, Amctpost) of the anterior and posterior corneal surfaces, and average distance from the Z axis to the apex (Dapexant, Dapexpost) and minimum thickness points (Dmctant, Dmctpost) of both corneal surfaces.ResultsSignificant differences among control and keratoconus group were found in Aapexant, Aapexpost, Amctant, Amctpost, Dapexant, Dapexpost (all p<0.001), Apost (p = 0.014), and Dmctpost (p = 0.035). Significant correlations in keratoconus group were found between Aant and Apost (r = 0.836), Amctant and Amctpost (r = 0.983), and Dmctant and Dmctpost (r = 0.954, all p<0.001). A logistic regression analysis revealed that the detection of keratoconus grade I (Amsler Krumeich) was related to Apost, Atot, Aapexant, Amctant, Amctpost, Dapexpost, Dmctant and Dmctpost (Hosmer-Lemeshow: p>0.05, R2 Nagelkerke: 0.926). The overall percentage of cases correctly classified by the model was 97.30%.ConclusionsOur morphogeometric approach based on the analysis of the cornea as a solid is useful for the characterization and detection of keratoconus.
| S-EPMC5590974 | biostudies-literature
Project description:There is consistent evidence that the principal etiology of schizophrenia involves predisposing genetic factors. Recent years have seen several new insights in the genetics of schizophrenia. Several chromosomal regions show significant evidence that they contain schizophrenia susceptibility genes. A clinically relevant genetic subtype of schizophrenia (22q deletion syndrome) has been identified. There is new evidence that spontaneous mutations may play a role. There are new recommendations for genetic counseling. The progress to date suggests that understanding of a neurodevelopmental pathway from genetic susceptibility to schizophrenia will soon be fundamentally altered by molecular genetic advances in this complex disease.
| S-EPMC3188303 | biostudies-literature
Project description:To evaluate the repeatability of corneal biomechanical parameters in normal and keratoconus eyes, and explore factors that affects the repeatability, and further assess the diagnostic ability of new parameters. Seventy-seven keratoconus eyes of 47 patients and 77 right eyes of 77 normal subjects were recruited in current study. All participants received three repeated measurements with 2 to 5?minutes interval. The interclass correlation coefficient (ICC), Cronbach' ? and repeatability coefficient (RC) were evaluated. The liner regression analysis was used to identify factors that affect the repeatability, and linear mixed effects model was performed to compare the parameters differences. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic ability of new parameters. Eighteen parameters in normal eyes and twenty-two parameters in keratoconus eyes showed excellent repeatability (ICC???0.90). Age, axial measurement (AL), spherical equivalent, astigmatism, gender, mean keratometry (Kmean), intraocular pressure (IOP) and central corneal thickness (CCT) could affect the repeatability of new Corvis ST parameters. Compared with normal eyes, the Ambrósio's Relational Thickness horizontal (ARTh), biomechanical corrected IOP (bIOP), stiffness parameter at first applanation (SP A1) were low and the Max Inverse Radius, deformation amplitude (DA) Ratio Max [2?mm], Pachy Slope, DA Ratio Max [1?mm], Integrated Radius and Corvis Biomechanical Index (CBI) were high in keratoconus eyes (All P?<?0.05). Both ARTh and CBI had high Youden index (0.870), and the corresponding cut-off values were 379.29 and 0.44. The repeatability of Corvis ST parameters was acceptable both in normal and keratoconus eyes, and new parameters could effectively diagnose keratoconus eyes from normal eyes.
| S-EPMC6814725 | biostudies-literature
Project description:Familial hypercholesterolemia (FH) is one of the most common monogenic diseases, leading to an increased risk of premature atherosclerosis and its cardiovascular complications due to its effect on plasma cholesterol levels. Variants of three genes (LDL-R, APOB and PCSK9) are the major causes of FH, but in some probands, the FH phenotype is associated with variants of other genes. Alternatively, the typical clinical picture of FH can result from the accumulation of common cholesterol-increasing alleles (polygenic FH). Although the Czech Republic is one of the most successful countries with respect to FH detection, approximately 80% of FH patients remain undiagnosed. The opportunities for international collaboration and experience sharing within international programs (e.g., EAS FHSC, ScreenPro FH, etc.) will improve the detection of FH patients in the future and enable even more accessible and accurate genetic diagnostics.
| S-EPMC7575810 | biostudies-literature
Project description:In juvenile idiopathic arthritis (JIA), there are now more than 25 regions represented by single nucleotide polymorphisms that show strong genetic associations. The causal variants and corresponding functions have not yet been defined for the majority of these regions. Here, we review current JIA association findings and the recent progress in the annotation of noncoding portion of the human genome as well as the new technologies necessary to apply this knowledge to JIA association findings.An international collaboration was able to amass sufficient numbers of JIA and control samples to identify significantly robust genetic associations for JIA. The Encyclopedia of DNA Elements project and the National Institutes of Health (NIH) Roadmap Epigenetics Program have now annotated more than 80% of the noncoding genome, important in understanding the impact of risk loci, the majority of which fall outside of protein coding regions. Recent technological advances in high throughput sequencing, chromatin structure determination, transcription factor and enhancer binding site mapping and genome editing will likely provide a basis for understanding JIA genetic risk.Understanding the role of genetic variation in the cause of JIA will provide insight for disease mechanism and may explain disease heterogeneity between JIA subtypes and between autoimmune diseases in general.
| S-EPMC4445412 | biostudies-literature
Project description:Ischemic stroke, white matter hyperintensities related to small vessel ischemia, and intracranial aneurysms all show heritability. This review focuses on recent progress in understanding the molecular genetics of these disorders. Also reviewed is recent progress in understanding single-gene disorders in which stroke is a major feature of the phenotype, including CADASIL, CARASIL, hereditary angiopathy with nephropathy, aneurysm and muscle cramps, and Fabry disease and progress in pharmacogenomics as it relates to response to antiplatelet therapy.
| S-EPMC3056067 | biostudies-literature