Congenital hereditary endothelial dystrophy - mutation analysis of SLC4A11 and genotype-phenotype correlation in a North Indian patient cohort

PURPOSE: To identify the solute carrier family 4 (sodium borate cotransporter) member 11 (SLC4A11) mutation spectrum and to perform genotype-phenotype correlations in autosomal recessive Congenital Hereditary Endothelial Dystrophy (CHED2) in North Indian patients. METHODS: Twenty-five patients from twenty families clinically diagnosed with autosomal recessive CHED2 were recruited for the study. Clinical parameters such as age at onset, presentation, and pre- and post-operative visual acuities were recorded. Corneal buttons of patients undergoing keratoplasty were analyzed for histopathologic and ultrastructural confirmation. All the affected individuals and 50 unrelated population matched normal controls were screened for underlying sequence changes. Genomic DNA was isolated from peripheral blood samples and all the exons and the 5′-upstream region of the SLC4A11 gene were screened for mutations by direct DNA sequencing. RESULTS: A high degree of consanguinity (9 out of 20 families) was noted. Corneal haze was reported to be present since birth or shortly thereafter in all affected patients. Histology and electron microscopy studies revealed increased thickness of Descemet’s membrane, especially of the non-banded zone. Molecular studies revealed one novel homozygous in-frame deletion mutation in two affected siblings from one family and three other previously reported homozygous mutations in 12 patients from 9 families. Mutations were not identified in 11 patients from 11 families. High interfamilial and intrafamilial phenotypic variability was seen among the cohort of patients. CONCLUSIONS: This is the first report on the mutation spectrum and genotype-phenotype correlation in CHED2 patients from North India. The present study detected one novel and three reported changes, adding to the repertoire of mutations in SLC4A11, and recorded a high degree of genetic heterogeneity in CHED2.