To report a phenotypic variant of lattice corneal dystrophy associated with tw o missense changes, Ala546Asp and Pro551Gln, in the transforming growth factor β induced gene (TGFBI). Experimental study. Genomic DNA wa...To report a phenotypic variant of lattice corneal dystrophy associated with tw o missense changes, Ala546Asp and Pro551Gln, in the transforming growth factor β induced gene (TGFBI). Experimental study. Genomic DNA was obtained from the proband as well as affected and unaffected family members. Exons 4, 11, 12, and 14 of the TGFBI gene were amplified and sequenced. Additionally, a corneal butto n excised from the proband was examined by light and transmission electron micro scopy. Haplotype analysis was performed on the probands family and members of a previously identified pedigree with the same TGFBI gene missense changes. Bila teral, symmetric, radially arranged, branching refractile lines within and surro unding an area of central anterior stromal haze were noted in the proband. Multi ple polymorphic, refractile deposits were noted in the mid and posterior stroma in both the proband and her daughter. Light and electron microscopic analyses de monstrated amyloid and excluded the presence of deposits characteristic of granu lar corneal dystrophy. Screening of TGFBI exon 12 in the proband and her affecte d daughter revealed two missense changes, Ala546Asp and Pro551Gln (both absent in 250 control chromosomes). Haplotype an alysis suggested that the mutations in this family and in a previously identifie d pedigree reflect a founder effect, rather than an independent occurrence. We p resent a phenotypic variant of lattice corneal dystrophy associated with the Ala 546Asp and Pro551Gln missense changes in exon 12 of the TGFBI gene. A common anc estor appears to account for the missense mutations observed in this pedigree an d in a previously reported family.展开更多
文摘To report a phenotypic variant of lattice corneal dystrophy associated with tw o missense changes, Ala546Asp and Pro551Gln, in the transforming growth factor β induced gene (TGFBI). Experimental study. Genomic DNA was obtained from the proband as well as affected and unaffected family members. Exons 4, 11, 12, and 14 of the TGFBI gene were amplified and sequenced. Additionally, a corneal butto n excised from the proband was examined by light and transmission electron micro scopy. Haplotype analysis was performed on the probands family and members of a previously identified pedigree with the same TGFBI gene missense changes. Bila teral, symmetric, radially arranged, branching refractile lines within and surro unding an area of central anterior stromal haze were noted in the proband. Multi ple polymorphic, refractile deposits were noted in the mid and posterior stroma in both the proband and her daughter. Light and electron microscopic analyses de monstrated amyloid and excluded the presence of deposits characteristic of granu lar corneal dystrophy. Screening of TGFBI exon 12 in the proband and her affecte d daughter revealed two missense changes, Ala546Asp and Pro551Gln (both absent in 250 control chromosomes). Haplotype an alysis suggested that the mutations in this family and in a previously identifie d pedigree reflect a founder effect, rather than an independent occurrence. We p resent a phenotypic variant of lattice corneal dystrophy associated with the Ala 546Asp and Pro551Gln missense changes in exon 12 of the TGFBI gene. A common anc estor appears to account for the missense mutations observed in this pedigree an d in a previously reported family.
