Heredity of Keratoconus

Willoughby, Colin E.; Lechner, Judith

doi:10.1007/978-3-642-28747-3_3

Cited by 1 publication

(5 citation statements)

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“…KC is a complex, genetically heterogeneous, multifactorial, degenerative disorder of the cornea [ 1 – 3 ]. Previous reports have detected more than 30 candidate genes and regions associated with KC [ 7 , 8 ]. However, because of the disease’s genetic heterogeneity and specificity, its genetic causes in most patients have not been effectively solved.…”

Section: Discussionmentioning

confidence: 99%

“…The genetic mode for KC development is autosomal dominant inheritance with incomplete exodominant or recessive inheritance [7,8]. KC studies among twins show that monozygotic twins display higher genetic consistency than heterozygotic twins, which proves that genetic factors have an important contribution towards the pathogenesis of KC [8,9].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, scholars have conducted much research on the genetic causes of KC. So far, more than 30 candidate genes and regions have been screened and identified by genome-wide linkage analysis, whole-exome sequencing (WES), or candidate gene sequencing [7,8,[10][11][12][13]. However, very few of these genes have been assessed for rare variation in keratoconus more broadly [14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have shown that genetic factors are involved in the KC development [ 2 , 6 , 7 ], and, thus, KC has a clear genetic tendency. About 6–10% of KC patients have a family history of KC, and its incidence in patients’ immediate relatives is 60 times higher than the incidence in people who are not immediate relatives of KC patients [ 8 ]. The genetic mode for KC development is autosomal dominant inheritance with incomplete exodominant or recessive inheritance [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…About 6–10% of KC patients have a family history of KC, and its incidence in patients’ immediate relatives is 60 times higher than the incidence in people who are not immediate relatives of KC patients [ 8 ]. The genetic mode for KC development is autosomal dominant inheritance with incomplete exodominant or recessive inheritance [ 7 , 8 ]. KC studies among twins show that monozygotic twins display higher genetic consistency than heterozygotic twins, which proves that genetic factors have an important contribution towards the pathogenesis of KC [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Multi-level consistent changes of the ECM pathway identified in a typical keratoconus twin’s family by multi-omics analysis

Hao

Chen

Zhang

et al. 2020

Orphanet J Rare Dis

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Background: Keratoconus (KC) is a common, degenerative disorder of the cornea, and genetic factors play a key role in its development. However, the genetic etiology of KC is still unclear. This study used the family of twins as material, using, for the first time, multi-omics analysis, to systematically display the changes in KC candidate factors in patients at the DNA, RNA, and protein levels. These can evaluate candidate pathogenic factors in depth and lock onto pathogenic targets. Results: The twins in this study presented classic phenotypes, clear diagnoses, complete case data, and clinical samples, which are excellent materials for genetically studying KC. Whole-exome sequencing was conducted on both the twins and their parents. Transcriptome sequencing was conducted on proband's and health individual's primary human corneal fibroblast cells. Quantitative Real-time PCR and western blot were used to validate the differential gene expressions between the proband and controls. By integrating genomics, transcriptome, and protein level data, multiple consecutive events of KC were systematically analyzed to help better understand the molecular mechanism and genetic basis of KC. The results showed that the accumulation of rare, micro-effect risk variants was the pathogenic factor in this Chinese KC family. Consistent changes in extracellular matrices (ECMs) at the DNA and RNA levels suggested that ECM related changes play a key role in KC pathogenesis. The major gene variants (WNT16, CD248, COL6A2, COL4A3 and ADAMTS3) may affect the expression of related collagens or ECM proteins, thus reducing the amount of ECM in corneas and resulting in KC. Conclusions: This study, the first to explore the genetic etiology of KC via multi-omics analysis under the polygenetic model, has provided new insights into the genetic mechanisms underlying KC and an effective strategy for studying KC pathogenesis in the future.

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