Gene mutation and genotype-phenotype description in corneal dystrophy associated with TGFBI genes
Xu Ke,Sun Xuguang,Xie Yue,Liang Qingfeng,Zhang Xiaohui,Jiang Feng,Li Yang
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Science Key Laboratory, Beijing 100005, China
Objective To investigate the TGFBI gene mutations of patients with corneal dystrophy and describe their phenotype specificity. Methods In a case series study, TGFBI genes were amplified by a polymerase chain reaction and directly sequenced for 63 patients. Each proband underwent clinical examination, including best-corrected visual acuity (BCVA) using E decimal charts, slit-lamp biomicroscopy, and confocal microscopy in some patients. Results Nine TGFBI gene heterozygosis missense mutations were found in 48 patients, including 8 reported pathogenic mutations:c.371G>A(p.R124H), c.370C>T(p.R124C), c.371G>T(p.R124L), c.1663C>T(p.R555W), c.1664G>A(p.R555Q), c.1514T>A(p.V505D), c.1859C>A(p.A620D), c.1877A>G(p.H626R) and one novel mutation: c.1694T>A(p.L565H). TGFBI gene mutations were most commonly located in exon 4 in 37 patients. The maximum proportion of the c.371G>A(p.R124H) mutation was in 28 cases with Avellino. The mean age of onset was 31.3±16.8 years (range 2-61 years). Slit-lamp biomicroscopy of 48 corneal dystrophies revealed bilateral opacity distributed in the corneal epithelium and stroma, expressing characteristic deposits. Conclusion Our findings expand the spectrum of TGFBI mutation. c.371G>A(p.R124H) is the most common form of mutation in Asian patients with corneal dystrophy. Different forms of mutations cause characteristic deposits. Based on the molecular genetics of corneal dystrophy, classification can improve the rate of clinical diagnosis.
Korvatska E, Munier FL, Chaubert P, et al. On the role of kerato-epithelin in the pathogenesis of 5q31-linked corneal dystrophies[J]. Invest Ophthalmol Vis Sci,1999,40(10):2213-2219.
Munier FL, Frueh BE, Othenin-Girard P, et al. BIGH3 mutation spectrum in corneal dystrophies[J]. Invest Ophthalmol Vis Sci,2002,43(4):949-954.
[4]
Lakshminarayanan R, Chaurasia SS, Murugan E, et al. Biochemical properties and aggregation propensity of transforming growth factor-induced protein (TGFBIp) and the amyloid forming mutants[J]. Ocul Surf,2015,13(1):9-25. DOI:10.1016/j.jtos.2014.04.003.
[5]
Zhang T, Yan N, Yu W, et al. Molecular genetics of Chinese families with TGFBI corneal dystrophies[J]. Mol Vis,2011,17:380-387.
[6]
Korvatska E, Munier FL, Djema A, et al. Mutation hot spots in 5q31-linked corneal dystrophies[J]. Am J Hum Genet,1998,62(2):320-324. DOI:10.1086/301720.
[7]
Munier FL, Korvatska E, Djemai A, et al. Kerato-epithelin mutations in four 5q31-linked corneal dystrophies[J]. Nat Genet, 1997,15(3):247-251. DOI:10.1038/ng0397-247.
[8]
Yamamoto S, Okada M, Tsujikawa M, et al. A kerato-epithelin (βig-h3) mutation in lattice corneal dystrophy type IIIA[J]. Am J Hum Genet,1998,62(3):719-722. DOI:10.1086/301765.
[9]
Afshari NA, Mullally JE, Afshari MA, et al. Survey of patients with granular, lattice, avellino, and Reis-Bücklers corneal dystrophies for mutations in the BIGH3 and gelsolin genes[J]. Arch Ophthalmol,2001,119(1):16-22. DOI:10-1001/pubs.Ophthalmol.-ISSN-0003-9950-119-1-ecs00039.
[10]
Okada M, Yamamoto S, Tsujikawa M, et al. Two distinct kerato-epithelin mutations in Reis-Bücklers corneal dystrophy[J]. Am J Ophthalmol,1998,126(4):535-542. DOI:http://dx.doi.org/10. 1016/S0002-9394(98)00135-4.
[11]
Tian X, Fujiki K, Wang W, et al. Novel mutation (V505D) of the TGFBI gene found in a Chinese family with lattice corneal dystrophy, type I[J]. Jpn J Ophthalmol,2005,49(2):84-88. DOI:10. 1007/s10384-004-0167-7.
[12]
Lakshminarayanan R, Vithana EN, Chai SM, et al. A novel mutation in transforming growth factor-beta induced protein (TGFβIp) reveals secondary structure perturbation in lattice corneal dystrophy[J]. Br J Ophthalmol,2011,95(10):1457-1462. DOI:10.1136/bjophthalmol-2011-300651.
Hirano K, Hotta Y, Fujiki K, et al. Corneal amyloidosis caused by Leu 518 Pro mutation of betaig-h3 gene[J]. Br J Ophthalmol, 2000,84(6):583-585. DOI:10.1136/bjo.84.6.583.
[15]
Mashima Y, Imamura Y, Konishi M, et al. Homogeneity of kerato-epithelin codon 124 mutations in Japanese patients with either of two types of cornealstromal dystrophy[J]. Am J Hum Genet,1997,61(6):1448-1450. DOI:10.1086/301649.
[16]
Chakravarthi SV, Kannabiran C, Sridhar MS, et al. TGFBI gene mutations causing lattice and granular corneal dystrophies in Indian patients[J]. Invest Ophthalmol Vis Sci,2005,46(1):121-125. DOI:10.1167/iovs.04-0440.
[17]
Aldave AJ, Rayner SA, Kim BT, et al. Unilateral lattice corneal dystrophy associated with the novel His572del mutation in the TGFBI gene[J]. Mol Vis,2006,12:142-146.
[18]
Atchaneeyasakul LO, Appukuttan B, Pingsuthiwong S, et al. A novel H572R mutation in the transforming growth factor-beta-induced gene in a Thai family with lattice corneal dystrophy type I[J]. Jpn J Ophthalmol,2006,50(5):403-408. DOI:10.1007/s10384-006-0357-6.
Mantelli F, Lambiase A, Di Zazzo A, et al. Sands of sahara after LASIK in avellino corneal dystrophy[J]. Case Rep Ophthalmol Med,2012,2012:413010. DOI:10.1155/2012/413010.
[21]
Awwad ST, Di Pascuale MA, Hogan RN, et al. Avellino corneal dystrophy worsening after laser in situ keratomileusis further clinicopathologic observations and proposed pathogenesis[J]. Am J Ophthalmol,2008,145(4):656-661. DOI:10.1016/j.ajo.2007.12.008.
[22]
Roh MI, Grossniklaus HE, Chung SH, et al. Avellino corneal dystrophy exacerbated after LASIK: scanning electron microscopic findings[J]. Cornea,2006,25(3):306-311. DOI:10.1097/01.ico.0000 183536.07275.9a.
[23]
Aldave AJ, Sonmez B, Forstot SL, et al. A clinical and histopathologic examination of accelerated TGFBIp deposition after LASIK in combined granular-lattice corneal dystrophy[J]. Am J Ophthalmol,2007,143(3):416-419. DOI:http://dx.doi.org/10. 1016/j.ajo.2006.11.056.
[24]
Weiss JS, M?覬ller HU, Lisch W, et al. The IC3D classification of the corneal dystrophies[J]. Cornea,2008,27 Suppl 2:S1-83. DOI: 10.1159/000324074.
浙公网安备 33030202001892号