Fuchs endothelial corneal dystrophy (FECD) is the most common genetic disorder of the corneal endothelium and accounts for a significant fraction of the corneal transplants performed in the United States yearly. Clinically, FECD is marked by thickening of ... Fuchs endothelial corneal dystrophy (FECD) is the most common genetic disorder of the corneal endothelium and accounts for a significant fraction of the corneal transplants performed in the United States yearly. Clinically, FECD is marked by thickening of Descemets membrane and excrescences, called guttae, that appear typically in the fourth or fifth decade. Disease progression results in decreased visual acuity as a result of increasing corneal edema, and end-stage disease is marked by painful epithelial bullae (summary by Riazuddin et al., 2013). For a discussion of genetic heterogeneity of FECD, see FECD1 (136800).
Riazuddin et al. (2013) studied a large 3-generation family in which 12 members, the majority of whom were in the sixth or seventh decade of life, fulfilled the phenotypic criteria for Fuchs corneal dystrophy but exhibited variable severity. ... Riazuddin et al. (2013) studied a large 3-generation family in which 12 members, the majority of whom were in the sixth or seventh decade of life, fulfilled the phenotypic criteria for Fuchs corneal dystrophy but exhibited variable severity.
Riazuddin et al. (2013) studied a large 3-generation family in which 12 members, the majority of whom were in the sixth or seventh decade of life, fulfilled the phenotypic criteria for Fuchs corneal dystrophy but exhibited variable severity. ... Riazuddin et al. (2013) studied a large 3-generation family in which 12 members, the majority of whom were in the sixth or seventh decade of life, fulfilled the phenotypic criteria for Fuchs corneal dystrophy but exhibited variable severity. After excluding linkage to known FECD loci and mutation in 3 FECD-associated genes, Riazuddin et al. (2013) performed genomewide linkage analysis that did not yield significant linkage, although 2 loci on chromosomes 3p and 15q showed positive signals under a multilocus model. Next-generation exome sequencing in 1 unaffected and 2 affected members of the family identified a heterozygous nonsense mutation in the AGBL1 gene (R1028X; 615496.0001) on chromosome 15q that segregated with disease in the family under the multilocus model. The R1028X variant was also found in 2 of 384 ethnically matched controls and in the NHLBI Exome Variant Server database; Riazuddin et al. (2013) noted, however, that the respective minor allele frequencies (MAFs) of 0.0026 and 0.0035 were below the greater than 4% prevalence of late-onset FECD in the US population. Sequencing of the AGBL1 gene in an unselected FECD cohort identified 2 additional unrelated individuals with the R1028X mutation as well as 3 unrelated FECD patients who were heterozygous for a missense mutation in the AGBL1 gene (C990S; 615496.0002). The C990S variant was not found in 384 ethnically matched controls, but was present in the NHLBI Exome Variant Server at a low MAF of 0.0025 in the European American population. Riazuddin et al. (2013) concluded that AGBL1 is a causative locus for late-onset FECD.