Genetic analysis of patients with Fuchs endothelial corneal dystrophy in India

Boomiraj Hemadevi,Namperumalsamy V Prajna,Muthiah Srinivasan,Jambulingam Arunkumar,Periasamy Sundaresan

doi:10.1186/1471-2415-10-3

Boomiraj Hemadevi, Namperumalsamy V Prajna + Show 3 more

Open Access

https://doi.org/10.1186/1471-2415-10-3

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Journal: BMC Ophthalmology	Publication Date: Feb 10, 2010
Citations: 47	License type: cc-by

Affiliation: Aravind Eye Hospital

Abstract

BackgroundMutations 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.MethodsEighty 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.ResultsScreening 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.ConclusionsThis 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.

Highlights

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)
We report for the first time, the results of mutation analysis of the COL8A2 gene in 80 unrelated patients with early onset & late onset FECD
Eighty unrelated patients with a diagnosis of either early or late-onset FECD were enrolled in the study

Summary

Introduction

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 known to cause late-onset FECD. We screened for COL8A2, SLC4A11 gene variants in Indian FECD patients. FECD is a degenerative, bilateral, often asymmetric and slowly progressive disorder [2]. It is characterized by a pleomorphic, attenuated, dysfunctional and degenerated corneal endothelium and the progressive formation of microscopic, refractile, posterior excrescences in the Descemet membrane (a collagen rich basal lamina) secreted by corneal endothelium, clinically known as FECD may show familial clustering but it is usually a sporadic condition [5,6].

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