Disease relevance of COL8A2

• Analysis of COL8A2 gene mutation in Japanese patients with Fuchs' endothelial dystrophy and posterior polymorphous dystrophy [1].
• In the L450W mutant, Descemet's membrane was several times thicker than normal and traversed by refractile strands and blebs that stained intensely for COL8A2, a feature also observed in late-onset FCD [2].
• Posterior polymorphous corneal dystrophy (PPCD, also known as PPMD) is a rare disease involving metaplasia and overgrowth of corneal endothelial cells [3].
• The objective of the study was to provide immunization policy decision makers with a risk-benefit analysis for pre-adolescents vaccination, for various scenarios regarding the existence and the strength of an association between hepatitis B vaccination and the occurrence of first episode of central demyelinating (FECD) disease [4].
• The FECD method was inexpensive although suitable for the enumeration of E. coli at higher contamination level (> 50 cfu/g) [5].

High impact information on COL8A2

• We previously mapped PPCD to a region (PPCD3) on chromosome 10 containing the gene that encodes the two-handed zinc-finger homeodomain transcription factor TCF8 [3].
• In patients with PPCD, these cells manifest in an epithelial morphology and gene expression pattern, produce an aberrant basement membrane, and, sometimes, spread over the iris and nearby structures in a way that increases the risk for glaucoma [3].
• Missense mutations in COL8A2, the gene encoding the alpha2 chain of type VIII collagen, cause two forms of corneal endothelial dystrophy [6].
• This group of conditions includes Fuchs' endothelial dystrophy of the cornea (FECD), one of the commonest indications for corneal transplantation performed in developed countries, posterior polymorphous dystrophy (PPCD) and the congenital hereditary endothelial dystrophies (CHED) [6].
• This suggests that the underlying pathogenesis of FECD and PPCD may be related to disturbance of the role of type VIII collagen in influencing the terminal differentiation of the neural crest derived corneal endothelial cell [6].

Chemical compound and disease context of COL8A2

• The indole and MUG indicators both applied to demonstrate E. coli with the ABP or FECD method proved to be equal in specificity [5].

Biological context of COL8A2

• Refinement of the critical region defined a 6-7 cM interval of chromosome 1p34.3-p32 within which lies the COL8A2 gene [6].
• All 21 cases with FCD and one with posterior polymorphous dystrophy were heterozygous for L450W, a novel point mutation in the COL8A2 gene [7].
• Multiple relatives were affected with PPMD with apparent autosomal dominant inheritance, but surprisingly, the PPMD, congenital hereditary endothelial dystrophy 1 (CHED1) and CHED2 loci on chromosome 20 and the collagen, type VIII, alpha-2 (COL8A2) gene were excluded by linkage and haplotype analyses [8].
• CONCLUSIONS: Early-onset COL8A2 L450W disease involves massive accumulation and abnormal assembly of collagen VIII within Descemet's membrane, a process that is presumed to begin during fetal development [2].
• All exons and intron-exon boundaries of the VSX1 and the COL8A2 genes were amplified by polymerase chain reaction and sequenced [9].

Anatomical context of COL8A2

• Corneal guttae in COL8A2 patients were small, rounded, and associated with the endothelial cell center [7].
• PURPOSE: To characterize histologically Descemet's membrane in an early-onset Fuchs corneal dystrophy (FCD) COL8A2 mutant and compare these findings with corneas from late-onset FCD and normal corneas [2].

Other interactions of COL8A2

• Inheritance of a novel COL8A2 mutation defines a distinct early-onset subtype of fuchs corneal dystrophy [7].
• RESULTS: Screening of the COL8A1 gene did not reveal sequence variants in any affected individuals from the 15 FECD families [10].
• METHODS: A corneal explant from a patient with the L450W COL8A2 mutation and others with late-onset disease were studied with antibodies to collagens IV, VIIIA1, VIIIA2, fibronectin, and laminin [2].
• A genome-wide search of a three-generation family with early-onset FECD demonstrated significant linkage with D1S2830 (Z(max) = 3.72, theta = 0.0) [6].

Analytical, diagnostic and therapeutic context of COL8A2

• METHODS: DNA extraction, PCR amplification, and direct sequencing of the COL8A1 and COL8A2 genes was performed in affected and unaffected members of 15 unrelated families with two or more members with late-onset FECD [10].

References