eye bulging
Conditions
Interventions
None listed
Sponsors
Erasmus MC, Universitair Medisch Centrum Rotterdam
Eligibility
Age
2 Years to 64 Years
Inclusion criteria
Inclusion criteria: Keratoconus patients suspect of monogenetic course of disease and their healthy and affected family members
Exclusion criteria
Exclusion criteria: keratoconus, non familial course
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Genomic DNA will be extracted from saliva and/or blood according to standard protocols. Genetic sequencing will be performed according to standard protocols and quality control of the Erasmus MC Human Genomics Facility HuGe-F. We will perform an extensive quality control procedure which includes filtering on coverage (>10x) and quality of the detection variants. Next, we will annotate the variants using wAnnovar (wANNOVAR (wglab.org)). Segregation analysis will be performed, with cases being carriers and controls being non-carriers. We will look for variants shared across families and/or within each family, and we will evaluate these variants based on the biological information available to us such as the gene function and involvement with other diseases. This will help us identify the most likely causal variants. In case of a suspected autosomal dominant inheritance pattern, we will focus on heterozygous variants. In case of a recessive inheritance pattern, we will focus on homozygous variants which are present in a heterozygous manner in the parents. As a first step, we will employ a candidate-gene approach using a panel of genes which previously have been associated with keratoconus. This will be followed by an open exome approach to identify new genes. To identify causal variants, we will perform a prioritization procedure using an allele frequency cut-off ( | — |
Secondary
| Measure | Time frame |
|---|---|
| Following ophthalmic imaging with Pentacam and Corvis, assessment of the scans will be performed using topographical maps and a selection of parameters provided by the default setting of the Pentacam and Corvis. Examples of such parameters are the degree of astigmatism, K1, K2, Kmax, final D and thinnest pachymetry. Corvis scans will also be analyzed in a similar fashion. For the assessment of the association of environmental and genetic risk factors, an analysis of lifestyle, ocular history and systemic involvement will be performed. Estimation of the heritability of corneal morphologic features as measured by Pentacam and Corvis will be performed, and an analysis of the morphologic features of the corneas of non-affected family members of keratoconus patients will also be carried out. The association of corneal parameters (measured be Corvis or Pentcaam) with specific genetic variants will be assessed as a part of this study as well. | — |
Countries
Netherlands
Outcome results
None listed