The TGFBI Gene Mutation Screening Of A Pedigree With Reis Bücklers Corneal Dystrophy

Background Corneal dystrophies (CDS) is a group of inherited disorders characterized by bilateral corneal opacity degeneration,according to anatomical location can be divided into different types, Reis-Bücklers corneal dystrophy (Reis-bucklers corneal dystrophy, RBCD) is inherited in an autosomal dominant fashion, which of Bowman's corneal dystrophy, was first described by Reis in 1917 as an annular dystrophy (dystrophia anularis). Bücklers re-examined the same pedigree in 1949 and showed that the histopathologic examination reveals deposits was esoinophilic on H&E staining, was congophilic, and did not stain with PAS. LM(Light microscope) examination reveal smoth-esten, rod-shaped and trapezoidal deposits similar to those in granular dystrophy, but the immune antibody response confirm that these are not the same kind of material. It presents with frequent recurrent erosions of early onset within the first decade years of life, and visual failure followed during childhood. Surgical intervention was necessary in all individuals. Thiel and Behnke described a similar corneal dystrophy in 1967 that presented with recurrent erosions, moderately reduced vision, autosomal dominant inheritance, and honeycomb shaped opacities at the level of Bowman's layer. Since the report of Thiel and Behnke, descriptions in the literature have varied in nomenclature and classification, rendering differentiation between autosomal dominant RBCD and TBCD difficult. Küchle et al.proposed that these dystrophies are indeed two distinct entities that differ markedly in their appearance at the slit-lamp, associated degree of visual loss, histopathological findings, transmission electron microscopy (TEM) features, and prognosis following corneal transplantation. In RBCD,the geographic opacification was seen at the level of Bowman's layer, and histopathology demonstrates band shaped granular, subepithelial deposits which stain intensely red with Masson trichrome. TEM reveals the presence of"rod shaped bodies". In contrast TBCD has honeycomb shaped opacities, a subepithelial fibrocellular layer interposed between the epithelium and stroma, stains less strongly with Masson trichrome and has"curly fibers"measuring 9-15nm indiameter present on TEM . While visual loss with RBCD is described as early and marked, with TBCD it is later and moderate. The recurrence of the dystrophy after corneal transplantation is noted to be early with RBCD and much later with TBCD. The transforming growth factor-beta induced(TGFBI), also known as BIGH3 mapped. Two laboratories discoverd independently that the protein produce of TGFBI is expressed in the cornea, during the same year TGFBI and three corneal dystrophy (lattic corneal dystrophy, LCD type1, granular dystrophy,GCD1, and Avellino corneal dystrophy, ACD) were mapped to human chromosome 5(5q31). The TGFBI gene contains 17 exons, encode 683 amino acids. To date, 33 mutations in the gene have been identified,with mutation at Arg124 accounting for over half of all the patients with this group of the corneal disorders. Foreign reports show RBCD linked to the R124L mutation, only the absence of several atypical case with the F540 and H626P, G623D, while the reports on RBCD few in china.Methods (1)A Chinese family with Reis-bucklers corneal dystrophy (RBCD) was investigated. All the coding exons of TGFBI gene were amplified by polymerase chain reaction and products were analyzed by direct sequencing. The results were compared with that of the other 3 normal members from the same family and 100 unrelated population-matched control individuals. (2)We searched for case reports and papers about RBCD since 1980 by Chinese Biology Medicine(CBM)and pubmed to summarized the genetic and clinical features.Results (1)Three patients with RBCD in this family showed a point mutation at nucleotide 371(G>T)compared with that of the normal controls, resulting in the substitution of glutamine for arginine at codon 124.Meanwhile the mutation was not found in the 3 normal individuals and 100 unrelated control samples. (2)The inherited pattern of RBCD was autosomal dominant. Most patients show a certain degree of similarity, but few families there are differences in patients with the disease phenotype(3)There is also a association between R124L genotypes and phenotypes of RBCD reported in china as reported aboard.Conclusions (1)The c.371G>A mutation of TGFBI gene seemed to be the pathologic cause of this Chinese family with RBCD. (2)The clinical manifestation of patients with RBCD was similarity, but the expressivity of the disease was obviously variability. (3)A clear correlation between genotypes and phenotypes of RBCD has not been found.