Late-onset Fuchs endothelial corneal dystrophy (FECD) shows genetic heterogeneity. Identification of SLC4A11 as a candidate gene for congenital hereditary endothelial dystrophy with similar corneal endothelial defects as FECD and reduced mRNA expression of SLC4A11 in the endothelium of FECD cases suggested that this gene may also be involved in pathogenesis of FECD. Mutations in SLC4A11 give rise to SLC4A11 protein marked by retention in the endoplasmic reticulum as a result of mis-folding. We screened 45 sporadic late-onset, 4 early-onset FECD patients and an early-onset autosomal dominant FECD family. We identified three previously unreported missense mutations: c.719G>C (p.W240S), c.1519G>A (p.V507I) and c.1304C>T (p.T434I) in unrelated individuals. These SLC4A11 mutants, expressed in HEK293 cells, had defects in either their cell surface expression or functional activity (rate of osmotically driven water flux). SLC4A11 mutations contribute to 11% (5/45) of sporadic late-onset FECD in the cohort studied. COL8A2, which causes some cases of early-onset FECD, was also screened in this cohort. No mutations were identified in COL8A2, in neither the late-onset cohort nor the early-onset family, suggesting genetic heterogeneity in this FECD family.

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Purpose:Fuchs endothelial corneal dystrophy (FECD) is a progressive degenerative disease of the corneal endothelium. It is genetically heterogeneous and follows either an autosomal dominant or sporadic pattern of inheritance. Here, we have explored the association of four previously reported intronic single nucleotide polymorphisms and intronic CTG repeat expansions in TCF4 gene to FECD in an Indian cohort.Methods:The cohort consisting of 52 sporadic late-onset cases, 5 early-onset cases, and 148 controls was taken for the study. rs2286812 and rs613872 were genotyped by allele specific polymerase chain reaction (ASPCR) and PCR-based restriction digestion, respectively; rs17595731 and rs9954153 were genotyped by Taqman assay using real-time PCR. The quantitative assessment of the CTG repeat region was performed by PCR/Sanger DNA sequencing. The repeats were assessed qualitatively by short tandem repeat and triplet repeat primed PCR assays. The statistical analysis was performed using two-tailed Fisher's exact probability test.Results:SNPsrs613872 (G/T) for the ‘G’ allele (P value: 4.57 × 10−5) and rs17595731 (C/T) for the ‘C’ allele (P value: 1.87 × 10−5), respectively, showed a significant association to sporadic late-onset FECD. CTG repeat expansions were found to be associated with FECD with a P value = 2.4 × 10−3.Conclusion:rs613872, rs17595731, and CTG repeat expansions in intronic region of TCF4 are associated with increased risk of sporadic late-onset FECD in the Indian cohort studied.

Purpose: To report the non-participation rates in a cross-sectional study, compare participants with non-participants, elucidate barriers for non-response and evaluate the influence of non-responders on the outcome measure. Methods: The Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study had 2 steps in which non- participation was possible. Step 1 was an estimation of fasting blood sugar at the participants’ homes, and step 2 a base hospital examination. The sociodemographic information was collected at the time of enumeration. The barriers against participation were noted at refusal. The data of the participants were compared with the urban Tamil Nadu population data from the 2001 census. Results: The non-participation rate was 3.6% in the field (step 1), and 13.9% at the base hospital (step 2). At step 1, older men and unemployed women had a lesser odds ratio for non-participation than younger age groups. At step 2, employment was significant for non-participation in men, and age between 50 and 59 years, illiteracy and unemployment in women. Conclusion: The barriers against participation differed between steps 1 and 2. The study participants were similar to the population of urban Tamil Nadu. Hence, the results of the study can be generalized to the urban Indian population.