Genetic analysis of patients with Fuchs endothelial corneal dystrophy in India.
BACKGROUND
Mutations in COL8A2 gene which encodes the collagen alpha-2 (VIII) chain have been identified in both familial and sporadic cases of Fuchs endothelial corneal dystrophy (FECD). Heterozygous mutations in the SLC4A11 gene are also known to cause late-onset FECD. Therefore we screened for COL8A2, SLC4A11 gene variants in Indian FECD patients.


METHODS
Eighty patients with clinically diagnosed FECD and 100 age matched normal individuals were recruited. Genomic DNA was isolated from peripheral blood leukocytes. Mutations in COL8A2, SLC4A11 coding regions were screened using bi-directional sequencing. Fischer's exact test or Pearson's chi squared test were used to predict the statistical association of genotypes with the phenotype.


RESULTS
Screening of COL8A2 gene revealed 2 novel c.1610G>A, c.1643A>G and 3 reported variations c.112G>A, c.464G>A and c.1485G>A. In SLC4A11 gene, novel c.1659C>T, c.1974C>T and reported c.405G>A, c.481A>C and c.639G>A variants were identified. However all the variations in both the genes were also present in unaffected controls.


CONCLUSIONS
This is the first study analysing COL8A2 gene in Indian patients with FECD. No pathogenic mutations were identified in COL8A2. Merely silent changes, which showed statistically insignificant association with FECD, were identified in the screening of SLC4A11 gene. These results suggest that COL8A2, SLC4A11 genes may not be responsible for FECD in patients examined in this study.
Hemadevi
Boomiraj
B
Department of Genetics, Dr G Venkataswamy Eye Research Institute, Aravind Medical Research Foundation, #1 Anna nagar, Madurai, Tamilnadu, India.
Srinivasan
Muthiah
M
Arunkumar
Jambulingam
J
Prajna
Namperumalsamy V
NV
Sundaresan
Periasamy
P
D000328:Adult; D027321:Anion Transport Proteins / Q000235:genetics*; D017920:Antiporters / Q000235:genetics*; D001483:Base Sequence; D024102:Collagen Type VIII / Q000235:genetics*; D005260:Female; D005642:Fuchs' Endothelial Dystrophy / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation
D027321:Anion Transport Proteins; D017920:Antiporters; C443712:COL8A2 protein, human; D024102:Collagen Type VIII; C425809:SLC4A11 protein, human