Whole-exome sequencing in familial keratoconus: the challenges of a genetically
            complex disorder

Magalhães, Otávio de Azevedo; Kowalski, Thayne Woycinck; Wachholz, Gabriela Elis; Schüler‐Faccini, Lavínia

doi:10.5935/0004-2749.20190087

Cited by 9 publications

(5 citation statements)

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“…Além disso, não foi possível detectar uma correlação genótipo-fenótipo completa, o que prediz que o ceratocone é uma enfermidade geneticamente heterogênea, como proposto por Magalhães e colaboradores 10 .…”

Section: Resultsunclassified

Ceratocone: uma revisão quanto ao diagnóstico e tratamento

Oliveira

Mota

2022

R. Saúde

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Ceratocone é uma doença que afeta a córnea, essa é um tecido do olho humano que apura a qualidade da imagem produzida na retina. Constitui-se de uma membrana convexa, translúcida, inervada, sensível, sendo o único tecido avascular do corpo humano que se situa na parte anterior do globo ocular. Foi realizada uma revisão sistemática da literatura, com base em 20 artigos escolhidos por sua importância, relevância e dados levantados, variando entre os anos de 1945 e 2019, com o uso dos bancos de dados Scielo, Pubmed e Lilacs. Bem como o uso da tomografia da córnea e do segmento anterior, estudada por Bruno de Freitas Valbon, et al. , parece ser um método eficaz para aumentar a sensibilidade e a especificidade do diagnóstico e detecção precoce da ectasia corneana do tipo ceratocone. Como também, Bernardo Teixeira Lopes, et al. , estudou o perfil de espessura horizontal detectando o ceratocone, com capacidade comparável aos índices mais complexos. O diagnóstico do ceratocone abrange uma cuidadosa análise da córnea, abrangendo mecanismos simples aos mais complexos. Já o tratamento, destaca-se o crosslinking como método terapêutico efetivo, até o transplante de córnea nos últimos casos.

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Section: Resultsunclassified

Ceratocone: uma revisão quanto ao diagnóstico e tratamento

Oliveira

Mota

2022

R. Saúde

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“…More than half of the genes were reported in one type of study or in single studies. A few genes, encoded chains of collagens ( COL5A1, COL4A3 , and COL4A4 ) ( 57 , 59 , 61 , 67 , 72 , 76 , 78 , 84 , 87 , 88 , 90 ), collagen cross-linking enzyme ( LOX ) ( 18 , 30 , 90 ), factor for the synthesis or organization of collagen fibers ( ZNF469 ) ( 27 , 32 , 34 , 46 , 47 , 62 , 65 ), and others ( MIR184 and VSX1 ) ( 6 , 7 , 16 , 19 , 24 , 40 , 56 , 82 , 85 ) were identified in different types of studies, such as pathogenic mutation analysis, polymorphism association analysis, and family-based linkage analysis. However, the occurrence rate of these gene mutations in the population was relatively low, and in many populations, it could not even be verified ( 25 , 195 – 202 ), which suggested that KC is genetically heterogeneous.…”

Section: Discussionmentioning

confidence: 99%

Systematically Displaying the Pathogenesis of Keratoconus via Multi-Level Related Gene Enrichment-Based Review

Hao

Gao

et al. 2022

Front. Med.

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Keratoconus (KC) is an etiologically heterogeneous corneal ectatic disorder. To systematically display the pathogenesis of keratoconus (KC), this study reviewed all the reported genes involved in KC, and performed an enrichment analysis of genes identified at the genome, transcription, and protein levels respectively. Combined analysis of multi-level results revealed their shared genes, gene ontology (GO), and pathway terms, to explore the possible pathogenesis of KC. After an initial search, 80 candidate genes, 2,933 transcriptional differential genes, and 947 differential proteins were collected. The candidate genes were significantly enriched in extracellular matrix (ECM) related terms, Wnt signaling pathway and cytokine activities. The enriched GO/pathway terms of transcription and protein levels highlight the importance of ECM, cell adhesion, and inflammatory once again. Combined analysis of multi-levels identified 13 genes, 43 GOs, and 12 pathways. The pathogenic relationships among these overlapping factors maybe as follows. The gene mutations/variants caused insufficient protein dosage or abnormal function, together with environmental stimulation, leading to the related functions and pathways changes in the corneal cells. These included response to the glucocorticoid and reactive oxygen species; regulation of various signaling (P13K-AKT, MAPK and NF-kappaB), apoptosis and aging; upregulation of cytokines and collagen-related enzymes; and downregulation of collagen and other ECM-related proteins. These undoubtedly lead to a reduction of extracellular components and induction of cell apoptosis, resulting in the loosening and thinning of corneal tissue structure. This study, in addition to providing information about the genes involved, also provides an integrated insight into the gene-based etiology and pathogenesis of KC.

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“…A genetic basis for atopy has been well described, and familial aggregation of KC can be explained by this indirect inherited cause [18,[70][71][72]. Although increased utilization of whole-genome/exome sequencing technologies and high-density single nucleotide polymorphism arrays, it was not possible to identify clear causal genetic variants in both familial and sporadic forms of KC [49][50][51]. Two recent comprehensive meta-analysis of KC prevalence and risk factors showed that eye rubbing, family history of KC, allergy, asthma, and eczema were the most important risk factors according to the available literature [73…”

Section: Discussionmentioning

confidence: 99%

“…Whole-exome sequencing in affected members of two nonrelated families was performed and found no common segregating rare variants among them, indicating genetic heterogeneity in the pathogenesis of KC [51]. The lack of successful gene identification highlights the more complex nature of this disorder.…”

Section: Keratoconus Genetics Updatementioning

confidence: 99%

The role of environment in the pathogenesis of keratoconus

Magalhães¹,

Gonçalves²,

Gatinel

2021

Current Opinion in Ophthalmology

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Purpose of reviewThis study was conducted to demonstrate the importance of the environment in keratoconus (KC) genesis. Recent findingsGenetic-related connective tissue disorders demonstrate the inconsistency of theories regarding KC pathogenesis since no corneal steepening was observed in the majority of these patients. Despite recent advances and decades of research into the genetics of KC, the identification of disease-causing KC genes has been frustrating. Variants found based on genome-wide and next-generation sequencing only seem to account for a small number of cases or play a limited role in KC pathogenesis.

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Whole-exome sequencing in familial keratoconus: the challenges of a genetically complex disorder

Cited by 9 publications

References 0 publications

Ceratocone: uma revisão quanto ao diagnóstico e tratamento

Ceratocone: uma revisão quanto ao diagnóstico e tratamento

Systematically Displaying the Pathogenesis of Keratoconus via Multi-Level Related Gene Enrichment-Based Review

The role of environment in the pathogenesis of keratoconus

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