Transforming growth factor β induced mutation‑associated phenotype in a Chinese family exhibiting lattice corneal dystrophy

Qu,Chao; Yu,Man; Guo,Xiaoxin; Li,Jing; Liu,Xiaoqi; Shi,Yi; Gong,Bo

doi:10.3892/br.2017.975

Transforming growth factor β induced mutation‑associated phenotype in a Chinese family exhibiting lattice corneal dystrophy

Authors:
- Chao Qu
- Man Yu
- Xiaoxin Guo
- Jing Li
- Xiaoqi Liu
- Yi Shi
- Bo Gong
View Affiliations

Affiliations: Sichuan Key Laboratory for Disease Gene Study, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, P.R. China, Department of Ophthalmology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, P.R. China
Published online on: August 30, 2017 https://doi.org/10.3892/br.2017.975
Pages: 314-318

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Lattice corneal dystrophy type I (LCDI) is associated with a large number of missense mutations in the transforming growth factor β induced (TGFBI) gene. The aim of the present study was to analyze TGFBI mutation in a Chinese family with LCDI, and to describe the clinical features and phenotype‑genotype correlation within this family. Three generations of this family with LCDI were enrolled in the current study. Complete ophthalmic examinations were performed on all family members and mutation screenings of the coding regions of TGFBI were analyzed using a direct sequencing method. All family members underwent slit‑lamp examination, and two patients and one of normal members in the family were evaluated by laser scanning in vivo confocal microscopy. A single heterozygous c.370C>T (p.R124C) mutation was identified in exon 4 of the TGFBI gene in five affected individuals, but not in the other family members and 400 normal control subjects. The affected members exhibited similar clinical features of LCDI, except that patient III:5 presented with mild symptoms. Confocal microscopy in vivo examination demonstrated that the proband (II:2) and his affected niece (III:4) had disruptions in multiple corneal layers, including the basal epithelial cells, stroma cells and Bowman's membrane. Thus, the R124C mutation in the TGFBI gene was identified in a Chinese family with LCDI. These results characterized the clinical features and revealed a genotype‑associated phenotype in this family, which may contribute to understanding the pathogenesis of LCDI.

View Figures

View References

1	Klintworth GK: The molecular genetics of the corneal dystrophies - current status. Front Biosci. 8:687–713. 2003. View Article : Google Scholar
2	Sacchetti M, Macchi I, Tiezzi A, La Cava M, Massaro-Giordano G and Lambiase A: Pathophysiology of corneal dystrophies: From cellular genetic alteration to clinical findings. J Cell Physiol. 231:261–269. 2016. View Article : Google Scholar : PubMed/NCBI
3	Weiss JS, Møller HU, Lisch W, Kinoshita S, Aldave AJ, Belin MW, Kivelä T, Busin M, Munier FL, Seitz B, et al: The IC3D classification of the corneal dystrophies. Cornea. 27 Suppl 2:S1–S83. 2008. View Article : Google Scholar : PubMed/NCBI
4	Schorderet D: Corneal dystrophies: Overview and summary. Prog Mol Biol Transl Sci. 134:73–78. 2015. View Article : Google Scholar : PubMed/NCBI
5	Klintworth GK: Advances in the molecular genetics of corneal dystrophies. Am J Ophthalmol. 128:747–754. 1999. View Article : Google Scholar : PubMed/NCBI
6	Lisch W and Seitz B: Lattice corneal dystrophy type 1: An epithelial or stromal entity? Cornea. 33:1109–1112. 2014. View Article : Google Scholar : PubMed/NCBI
7	Lakshminarayanan R, Chaurasia SS, Anandalakshmi V, Chai SM, Murugan E, Vithana EN, Beuerman RW and Mehta JS: Clinical and genetic aspects of the TGFBI-associated corneal dystrophies. Ocul Surf. 12:234–251. 2014. View Article : Google Scholar : PubMed/NCBI
8	Munier FL, Frueh BE, Othenin-Girard P, Uffer S, Cousin P, Wang MX, Héon E, Black GC, Blasi MA, Balestrazzi E, et al: BIGH3 mutation spectrum in corneal dystrophies. Invest Ophthalmol Vis Sci. 43:949–954. 2002.PubMed/NCBI
9	Dudakova L, Palos M, Jirsova K, Skalicka P, Dundr P and Liskova P: Novel TGFBI mutation p.(Leu558Arg) in a lattice corneal dystrophy patient. Ophthalmic Genet. 37:473–474. 2016. View Article : Google Scholar : PubMed/NCBI
10	Chae H, Kim M, Kim Y, Kim J, Kwon A, Choi H, Park J, Jang W, Lee YS, Park SH and Kim MS: Mutational spectrum of Korean patients with corneal dystrophy. Clin Genet. 89:678–689. 2016. View Article : Google Scholar : PubMed/NCBI
11	Cai J, Zhu L, Zha Y and Kang Q: TGFBI gene mutation analysis in Chinese families with corneal dystrophies. Genet Test Mol Biomarkers. 20:388–392. 2016. View Article : Google Scholar : PubMed/NCBI
12	Ann LB, Abbouda A, Frausto RF, Huseynli S, Gupta K, Alió JL and Aldave AJ: Variant lattice corneal dystrophy associated with compound heterozygous mutations in the TGFBI gene. Br J Ophthalmol. 101:509–513. 2017. View Article : Google Scholar : PubMed/NCBI
13	Costagliola C, Romano V, Cifariello F, Aceto F and Porcellini A: Lattice corneal dystrophy: A report of two cases in twin sisters due to 3 mutations (T1620C, C1416T, A1924G) in the TGFBI (BIGH3) gene. Clin Ter. 165:e73–e75. 2014.PubMed/NCBI
14	Hellenbroich Y, Tzivras G, Neppert B, Schwinger E and Zühlke C: R124C mutation of the betaIGH3 gene leads to remarkable phenotypic variability in a Greek four-generation family with lattice corneal dystrophy type 1. Ophthalmologica. 215:444–447. 2001. View Article : Google Scholar : PubMed/NCBI
15	Yoshida S, Yoshida A, Nakao S, Emori A, Nakamura T, Fujisawa K, Kumano Y and Ishibashi T: Lattice corneal dystrophy type I without typical lattice lines: Role of mutational analysis. Am J Ophthalmol. 137:586–588. 2004. View Article : Google Scholar : PubMed/NCBI
16	El-Ashry MF, El-Aziz Abd MM, Ficker LA, Hardcastle AJ, Bhattacharya SS and Ebenezer ND: BIGH3 mutation in a Bangladeshi family with a variable phenotype of LCDI. Eye (Lond). 18:723–728. 2004. View Article : Google Scholar : PubMed/NCBI
17	Liu Z, Wang YQ, Gong QH and Xie LX: An R124C mutation in TGFBI caused lattice corneal dystrophy type I with a variable phenotype in three Chinese families. Mol Vis. 14:1234–1239. 2008.PubMed/NCBI
18	Courtney DG, Poulsen ET, Kennedy S, Moore JE, Atkinson SD, Maurizi E, Nesbit MA, Moore CB and Enghild JJ: Protein composition of TGFBI-R124C- and TGFBI-R555W-associated aggregates suggests multiple mechanisms leading to lattice and granular corneal dystrophy. Invest Ophthalmol Vis Sci. 56:4653–4661. 2015. View Article : Google Scholar : PubMed/NCBI
19	Yang QN, Zhao YW, Guo LH, Yan NH, Liu XY and Cai SP: Arg124Cys mutation of the TGFBI gene in a Chinese pedigree of Reis-Bücklers corneal dystrophy. Int J Ophthalmol. 4:235–238. 2011.PubMed/NCBI
20	Runager K, Enghild JJ and Klintworth GK: Focus on molecules: Transforming growth factor beta induced protein (TGFBIp). Exp Eye Res. 87:298–299. 2008. View Article : Google Scholar : PubMed/NCBI