Congenital Hereditary Endothelial Dystrophy (CHED) is a heritable bilateral disorder of the corneal endothelium, resulting from hypoplasia or degeneration and dysfunction of the endothelial cells. CHED can be inherited in an autosomal dominant or autosomal recessive manner. Autosomal recessive CHED is a rare disorder presenting at birth or in early childhood, and is characterized by a diffuse ground-glass appearance of the corneas and marked corneal thickening from birth with nystagmus and blurred vision. The clinical diagnosis of CHED is based on the presence of a diffuse corneal edema in the absence of any other anterior segment abnormality. Penetrating keratoplasty is the most preferred treatment for the patients even in advanced stages of the disease, which can provide marked visual improvement.
Homozygous mutations in the SLC4A11 (Sodium Bicarbonate Transporter?like Solute Carrier Family 4 Member 11) gene are associated with CHED. These mutations result in loss of protein function either by impeding membrane targeting or by nonsense-mediated decay.
Chai et al. (2010) identified a novel missense mutation (p.G394R) in the SLC4A11 gene in a consanguineous Qatari family affected with recessive congenital hereditary endothelial dystrophy.
Shah et al. (2008) studied nine members of a Saudi family with autosomal recessive CHED for disease-causing mutations in the SLC4A11 gene. A novel, homozygous mutation in the SLC4A11 gene (p.Thr271Met) was detected in the proband and all affected members of the family.
Aldahmesh et al. (2009) studied the extent of allelic heterogeneity in congenital hereditary endothelial dystrophy in 10 patients representing seven unrelated, but consanguineous families. All 10 patients were homozygous at the SLC4A11 locus. Seven mutations were identified, five of which are novel. The mutation spectrum included missense [c.1228GT), splice site (c.2114+1G>A), and small deletions [one out-of-frame (c.520delGCTTCGCC resulting in a premature termination atAsp164X, and one intronic deletion (c.1044+25del19nt)]. Aldahmesh et al. (2009) concluded that there was no evidence of a genetic heterogeneity in CHED in Saudis and that loss of BTR1 function is the most likely mutational mechanism causing the disease in the population.