Analysis of COL8A2 Gene Mutation in Japanese Patients with Fuchs’ Endothelial Dystrophy and Posterior Polymorphous Dystrophy

Abstract

The R155Q and T502M mutations of COL8A2 may not be the causative defect in the Japanese FECD and PPMD patients examined in this study.

Q455V mutation in COL8A2 is associated with Fuchs' corneal dystrophy in Korean patients

“…8,10,11 On the basis of studies reporting significant linkage of FECD, several pathogenic mutations in the collagen type VIII a2 gene (COL8A2), located on 1p34.3-p32, have been detected in affected individuals with FECD, and a strong association between FECD patients and genetic variants of COL8A2 has been validated by multiple studies. [6][7][8]12 In particular, two missense mutations, L450W and Q455K, showed perfect concordance in an FECD family having early onset and are positioned within the triple-helical domain of a2 collagen type VIII, which leads to the structural alteration of Descemet's membrane. 6,8,13,14 Also, in English FECD patients, three missense mutations of the COL8A2 gene, R155Q, R304Q, and R434H, were identified in familial and unrelated forms of common FECD, 8 whereas Aldave et al (2006) and Kobayashi et al (2004) reported that no COL8A2 variants associated with the common FECD subtype, late-onset FECD have been identified.…”

“…[6][7][8]12 In particular, two missense mutations, L450W and Q455K, showed perfect concordance in an FECD family having early onset and are positioned within the triple-helical domain of a2 collagen type VIII, which leads to the structural alteration of Descemet's membrane. 6,8,13,14 Also, in English FECD patients, three missense mutations of the COL8A2 gene, R155Q, R304Q, and R434H, were identified in familial and unrelated forms of common FECD, 8 whereas Aldave et al (2006) and Kobayashi et al (2004) reported that no COL8A2 variants associated with the common FECD subtype, late-onset FECD have been identified. 15 Furthermore, an observed association between the COL8A2 gene variants and FECD, as well as other corneal diseases, including keratoconus and posterior polymorphous corneal dystrophy (PPCD), was reported by others.…”

“…15 Furthermore, an observed association between the COL8A2 gene variants and FECD, as well as other corneal diseases, including keratoconus and posterior polymorphous corneal dystrophy (PPCD), was reported by others. 6,8,12,15 Therefore, it is important to identify the genetic factors that determine susceptibility to FECD to gain an insight into the pathogenesis of FECD in Korean patients, because the susceptibility of mutations in COL8A2 can vary in different ethnicities and in the age of onset. 8,12,[15][16][17] The association between variations in the COL8A2 gene and Korean FECD patients is yet to be investigated.…”

“…6,8,12,15 Therefore, it is important to identify the genetic factors that determine susceptibility to FECD to gain an insight into the pathogenesis of FECD in Korean patients, because the susceptibility of mutations in COL8A2 can vary in different ethnicities and in the age of onset. 8,12,[15][16][17] The association between variations in the COL8A2 gene and Korean FECD patients is yet to be investigated. In this study, we screened the COL8A2 gene for both familial and unrelated FECD patients to determine whether mutations in COL8A2 are responsible for causing FECD in a Korean population.…”

Polymorphisms of the Apoptosis-Related FAS and FAS Ligand Genes in Keratoconus and Fuchs Endothelial Corneal Dystrophy

“…Linkage studies of large multigenerational families with late-onset FECD identified several chromosomal regions on chromosomes 1, 5, 8 and X to be associated with the disease (Sundin et al 2006a, b;Afshari et al 2009). A strong association between FECD and genetic variants of the COL8A2 (collagen type VIII α2) gene was reported (Biswas et al 2001;Kobayashi et al 2004;Gottsch et al 2005).…”