title: Q455V mutation in COL8A2 is associated with Fuchs' corneal dystrophy in Korean patients.
abstract: OBJECTIVE
  To investigate the possibility of collagen type VIII alpha2 (COL8A2) as a potential susceptibility gene for Korean patients with Fuchs' corneal dystrophy (FECD), we performed mutation screening of the COL8A2 gene.
  
  
  METHODS
  A total of 25 FECD patients were screened, including 15 patients from six pedigrees with early onset FECD and an additional 10 unrelated patients, all of Korean ancestry. Seventy-three control individuals without corneal disease were selected from the general population. PCR-SSCP and direct sequencing were used to screen genetic variations in COL8A2. The pathogenic impact of these sequence variants was evaluated through the SIFT and PolyPhen algorithms.
  
  
  RESULTS
  We have identified a novel heterozygous mutation, Q455V, in exon 2 of COL8A2. All patients of Korean pedigrees with FECD had the Q455V mutation, and two out of nine unrelated cases also had this mutation. But it was not present in unaffected individuals from these pedigrees or from control groups. Two heterozygous missense mutations, R155Q and T502M, were also observed, but, they showed no significant difference between FECD patients and controls. The allele frequencies of A35A and G495G, which were synonymous substitutions, were significantly associated with FECD. Both Q455V and T502M were predicted as deleterious mutations by computational methods using PolyPhen and SIFT.
  
  
  CONCLUSIONS
  Our data constitute the first report of a heterozygous Q455V mutation of the COL8A2 gene in Korean patients with FECD. Q455V may be the causative defect in the development and progression of Korean FECD patients.
authors.affiliation: Laboratory of Ophthalmology and Visual Science, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: J-W
authors.initials: JW
authors.lastname: Mok
authors.forename: H-S
authors.initials: HS
authors.lastname: Kim
authors.forename: C-K
authors.initials: CK
authors.lastname: Joo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics*; D024102:Collagen Type VIII / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005642:Fuchs' Endothelial Dystrophy / Q000235:genetics* / Q000473:pathology; D005787:Gene Frequency; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D055815:Young Adult
chemical_list: C443712:COL8A2 protein, human; D024102:Collagen Type VIII