Similar articles

Abstract: In this paper, we report the clinical and molecular features of the distinct TGFBI (human transforming growth factor β-induced, OMIM No. 601692) gene-linked corneal dystrophy. Altogether, five pedigrees and ten unrelated individuals diagnosed as corneal dystrophy were recruited. Peripheral venous DNA was extracted, and then amplified by polymerase chain reaction (PCR) and scanned for mutation by single-stranded conformation polymorphism (SSCP). Direct DNA sequencing was used to analyze the mutations of the TGFBI gene. In our study, thirty patients from five pedigrees and ten sporadic patients were diagnosed as four TGFBI gene-linked corneal dystrophies of granular corneal dystrophy type I (GGCD I), Avellino corneal dystrophy (ACD), lattice corneal dystrophy type I (LCD I), and lattice corneal dystrophy type IIIA (LCD IIIA), and in total, seven disease-causing mutations, namely R555W, A546D, A546T, and T538P mutations in exon 12, R124H and R124C mutations in exon 4, and P501T mutation in exon 11, were identified, while four polymorphisms of V327V, L472L, F540F, and 1665–1666insC were screened in exons 8, 11, and 12. The study ascertained the tight genotype-phenotype relationship and confirmed the clinical and genetic features of four TGFBI gene-linked corneal dystrophies.

[1]Biswell, R., 1999. Cornea. In: Vaughan, D., Asbury, T., Riordan-Eva, P. (Eds.), General Ophthalmology, 15th Ed. Appleton & Lange, Stamford, p.119-141.

[2]Chakravarthi, S., Kannabiran, C., Sridhar, M.S., Vemuganti, G.K., 2005. TGFBI gene mutations causing lattice and granular corneal dystrophies in Indian patients. Invest. Ophthalmol. Vis. Sci., 46(1):121-125.

[3]Chen, L.L., Yu, P., Gu, Y.S., Yang, Y.H., Yan, X.Y., Ge, Z., Lv, N., Guo, L., 2005. Granular corneal dystrophy with Arg555Trp mutation in the BIGH3 gene. Chin. Ophthal. Res., 23(1):60-62 (in Chinese).

[4]Clout, N.J., Hohenester, E., 2003. A model of FAS1 domain 4 of the corneal protein β(ig)-h3 gives a clearer view on corneal dystrophies. Mol. Vis., 9(11):440-448.

[5]Dong, W.L., Zou, L.H., Pang, Z.Q., Jin, T., Yu, J., 2005. Molecular-genetic analysis of Chinese patients with lattice corneal dystrophy in the BIGH3 gene. Chin. J. Ophthalmol., 41(6):523-526 (in Chinese).

[6]Kannabiran, C., Klintworth, G.K., 2006. TGFBI gene mutations in corneal dystrophies. Hum. Mutat., 27(7):615-625.

[7]Kim, J.E., Kim, E.H., Han, E.H., Park, R.W., Park, I.H., Jun, S.H., Kim, J.C., Young, M.F., Kim, I.S., 2000. A TGF-β-inducible cell adhesion molecule, β(ig)-h3, is downregulated in melorheostosis and involved in osteogenesis. J. Cell. Biochem., 77(2):169-178.

[8]Kim, J.E., Park, R.W., Cboi, J.Y., Bae, Y.C., Kim, K.S., Joo, C.K., Kim, I.S., 2002. Molecular properties of wild-type and mutant BIGH3 proteins. Invest. Ophthalmol. Vis. Sci., 43(3):656-661.

[9]Klintworth, G.K., 1999. Advances in the molecular genetics of corneal dystrophies. Am. J. Ophthalmol., 128(6):747-754.

[10]Klintworth, G.K., 2003. The molecular genetics of corneal dystrophies—current status. Front. Biosci., 8(1-3):d687-d713.

[11]Kochairi, I.E., Letovanec, I., Uffer, S., Munier, F.L., Chaubert, P., Schorderet, D.F., 2006. Systemic investigation of kerato-epithelin deposits in TGFBI/BIGH3-related corneal dystrophy. Mol. Vis., 12(10):461-466.

[12]Korvatska, E., Munier, F.L., Djemai, A., Wang, M.X., Frueh, B., Chiou, A.G.Y., Uffer, S., Ballestrazzi, E., Braunstein, R.E., Forster, R.K., et al., 1998. Mutation hot spots in 5q31-linked corneal dystrophies. Am. J. Hum. Genet., 62(2):320-324.

[13]Mashima, Y., Konishi, M., Nakamura, Y., Imamura, Y., Yamada, M., Ogata, T., Kudoh, J., Shimizu, N., 1998. Severe form of juvenile corneal dystrophy with homozygous R124H mutation in the kerato-epithelin gene in five Japanese patients. Br. J. Ophthalmol., 82(11):1280-1284

[14]Munier, F.L., Korvatska, E., Djema, A., le Paslier, D., Zografos, L., Pescia, G., Schorderet, D.F., 1997. Kerato-epithelin mutations in four 5q31-linked corneal dystrophies. Nat. Genet., 15(3):247-251.

[15]Munier, F.L., Frueh, B.E., Othenin-Girard, P., Uffer, S., Cousin, P., Wang, M.X., Héon, E., Black, G.C., Blasi, M.A., Ballestrazzi, E., et al., 2002. BIGH3 mutation spectrum in corneal dystrophies. Invest. Ophthalmol. Vis. Sci., 43(4):949-954.

[16]Okada, M., Yamamoto, S., Tsujikawa, M., Watanabe, H., Inoue, Y., Maeda, N., Shimomura, Y., Nishida, K., Quantock, A.J., Kinoshita, S., et al., 1998a. Two distinct kerato-epithelin mutations in Reis-Bucklers corneal dystrophy. Am. J. Ophthalmol., 26(4):535-542.

[17]Okada, M., Yamamoto, S., Watanabe, H., Inoue, Y., Tsujikawa, M., Maeda, N., Shimomura, Y., Nishida, K., Kinoshita, S., Tano, Y., 1998b. Granular corneal dystrophy with homozygous mutations in the kerato-epithelin gene. Am. J. Ophthalmol., 126(2):169-176.

[18]Schmitt-Bernard, C.F., Chavanieu, A., Herrada, G., Subra, G., Arnaud, B., Demaille, J.G., Calas, B., Argiles, A., 2002. BIGH3 (TGFBI) Arg124 mutations influence the amyloid conversion of related peptides in vitro: implications in the BIGH3-linked corneal dystrophies. Eur. J. Biochem., 269(21):5149-5156.

[19]Thapa, N., Lee, B.H., Kim, I.S., 2007. TGFBIp/βig-h3 protein: a versatile matrix molecular induced by TGF-β. Int. J. Biochem. Cell Biol., 39(12):2183-2194.

[20]Yu, P., Gu, Y.S., Yang, Y.H., Yan, X.Y., Chen, L.L., Ge, Z., Qi, M., Si, J.M., Guo, L., 2006. A clinical and molecular-genetic analysis of Chinese patients with lattice corneal dystrophy and novel Thr538Pro mutation in the TGFBI (BIGH3) gene. J. Genet., 85(1):73-76.

[21]Yu, P., Gu, Y.S., Jin, F., Hu, R.R., Chen, L.L., Yan, X.Y., Yang, Y.H., Qi, M., 2008. p.Ala546>Asp and Arg555>Trp mutations of TGFBI gene and their clinical manifestations in two large Chinese families with granular corneal dystrophy type I. Genetic Testing, 12(3):421-426.

[22]Zenteno, J.C., Ramirez-Miranda, A., Santacruz-Valdes, C., Suarez-Sanchez, R., 2006. Expanding the mutational spectrum in TGFBI-linked corneal dystrophies: identification of a novel and unusual mutation (Val113Ile) in a family with granular dystrophy. Mol. Vis., 12(10):331-335.