Double mutation (R124H, N544S) of TGFBI in two sisters with combined expression of Avellino and lattice corneal dystrophies

PURPOSE: The R124H mutation of the keratoepithelin gene (TGFBI) causes Avellino corneal dystrophy whereas the N544S mutation of this same gene gives rise to lattice corneal dystrophy. We now report two cases with both R124H and N544S mutations of TGFBI. METHODS: Genomic DNA and cDNA were isolated from the proband and family members and were subjected to polymerase chain reaction–mediated amplification of exons 1–17 of TGFBI. The amplification products were directly sequenced. Allele-specific cloning and sequencing were applied to evaluate the compound heterozygous mutation. RESULTS: Molecular genetic analysis revealed that the proband and one sister harbored both a heterozygous CGC→CAC (Arg→His) mutation at codon 124 and a heterozygous AAT→AGT (Asn→Ser) mutation at codon 544 of TGFBI. Slit-lamp examination revealed multiple granular regions of opacity and lattice lines in the corneal stroma of the proband and her sister with the double mutation. Allele-specific cloning and sequencing revealed that the R124H and N544S mutations are on different chromosomes. CONCLUSIONS: As far as we are aware, this is the first report of a patient with a double mutation (R124H, N544S) of TGFBI causing an autosomal dominant form of corneal dystrophy. The clinical manifestations of the two cases with both R124H and N544S mutations appeared to be a summation of Avellino and lattice corneal dystrophies.