Mutational spectrum of the SLC4A11 gene in autosomal recessive congenital hereditary endothelial dystrophy.

PURPOSE Autosomal recessive congenital hereditary endothelial dystrophy (AR-CHED or CHED2) is a bilateral corneal disorder manifesting at birth or in early childhood. CHED2 is caused by mutations in the sodium bicarbonate transporter-like solute carrier family 4 member 11 (SLC4A11) gene on chromosome 20p13. We screened 42 unrelated families with CHED2 in order to establish the spectrum of mutations in SLC4A11 and to look for genotype-phenotype correlations. METHODS Forty-two families (49 affected and 73 unaffected members) with recessive CHED were recruited according to predefined diagnostic criteria. Clinical data including age at onset and presentation, pre- and post-operative visual acuities, and presence of nystagmus were taken from patient records. Histopathologic parameters such as corneal thickness, Descemet membrane thickness, and endothelial cell counts were assessed on corneal sections. DNA from patients was screened for sequence changes by polymerase chain reaction (PCR)-amplification of coding regions of SLC4A11 and single strand conformation polymorphism analysis followed by sequencing. Sequence changes found were tested in 50 unrelated normal controls. RESULTS Twenty-seven different mutations were identified in 35 unrelated families, 19 of which were not previously reported. The mutations identified consisted of 13 missense, 5 nonsense, 7 deletions, 1 complex (deletion plus insertion) mutation, and 1 splice site mutation. Both mutant alleles were identified in 33 families and only one mutant allele in two families. No correlations were evident between clinical or histopathologic parameters and SLC4A11 mutations. CONCLUSIONS These data add to the mutational repertoire of SLC4A11 and establish the high degree of mutational heterogeneity in autosomal recessive CHED.