Clinical observation and gene mutation detection in a pedigree of retinal lattice degeneration combined with granular corneal dystrophy_Chinese Journal of Ocular Fundus Diseases

Authors：

Chen Chunli , Zhang Xiang , Lyu Jiao , Tian Tian , Peng Jie , Jin Haiying , Zhang Qi ,  Zhao Peiquan

Department of Ophthalmology, Xinhua Hospital, Affiliated to Medicine School of Shanghai Jiaotong University, Shanghai 200092, China (Chen Chunli, now working at Department of Ophthalmology, Shengli Oilfield Central Hospital and Department of ophthalmology, Tianjin Medical University Eye Hospital);

Corresponding author：

Zhao Peiquan, Email: zhaopeiquan@126.com

Keywords：

Corneal dystrophies, hereditary; Retinal degeneration; Mutation; Gene, TGFBI

DOI：

10.3760/cma.j.issn.1005-1015.2018.01.012

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Objective To investigate the clinical manifestations and gene mutation of a pedigree with retinal lattice degeneration and granular corneal dystrophy (GCD) type 2. Methods Ten members in 3 generations of a pedigree with retinal lattice degeneration and GCD2 were included in the study, including 6 patients (3 males and 3 females) and 4 healthy family members. All members underwent visual acuity, slit lamp microscope, three-mirror lens, fundus color photography, optical coherence tomography, and corneal endothelial cells counting. Genomic DNA was extracted from peripheral venous blood (2 ml) from all the subjects and their spouses, who had no related inherited diseases. The next generation sequencing method was used to detect the mutation sites of transforming growth factor β (TGFBI), and all results underwent Sanger verification. Results Among the 12 eyes of 6 patients, the visual acuity was FC/20 cm-1.0. In the superficial central corneal stroma, snowflake-like deposits were observed in three cases (6 eyes), and a small amount of granular deposits were observed in three cases (6 eyes). Corneal endothelial cell counts were normal. Retinal lattice degeneration were observed in 3 cases, 6 eyes (including 3 cases of rhegmatogenous retinal detachment in 4 eyes); retinal thinning without obvious lattice degeneration in 4 eyes of 2 patients. Nystagmus in 1 patient and fundus examination showed no significant abnormalities. DNA sequencing results showed that the proband and 4 patients had missense mutation of TGFBI gene in exon 4 c.371G＞ A, the mutation site corresponding to the amino acid change encoded by TGFBI gene No. 124 Amino acids, from arginine to histidine (p.R124H). Patients with this mutation have varying degrees of clinical phenotype. Conclusions The mutation of c.701G＞ A (p.R124H) in TGFBI gene is the causative gene of GCD in this pedigree. The patients with this mutation have different clinical phenotypes.

Citation： Chen Chunli, Zhang Xiang, Lyu Jiao, Tian Tian, Peng Jie, Jin Haiying, Zhang Qi, Zhao Peiquan. Clinical observation and gene mutation detection in a pedigree of retinal lattice degeneration combined with granular corneal dystrophy. Chinese Journal of Ocular Fundus Diseases, 2018, 34(1): 47-50. doi: 10.3760/cma.j.issn.1005-1015.2018.01.012 Copy

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5.	Kim HS, Yoon SK, Cho BJ, et al. BIGH3 gene mutations and rapid detection in Korean patients with corneal dystrophy[J]. Cornea, 2001, 20(8): 844-849. DOI: 10.1097/00003226-200111000-00013.
6.	Evans CJ, Davidson AE, Carnt N, et al. Genotype-phenotype correlation for TGFBI corneal dystrophies identifies p.(G623D) as a novel cause of epithelial basement membrane dystrophy[J]. Invest Ophthalmol Vis Sci, 2016, 57(13): 5407-5414. DOI: 10.1167/iovs.16-19818.
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9.	Yang J, Han X, Huang D, et al. Analysis of TGFBI gene mutations in Chinese patients with corneal dystrophies and review of the literature[J]. Mol Vis, 2010, 16: 1186-1193.
10.	Skonier J, Neubauer M, Madisen L, et al. cDNA cloning and sequence analysis of beta ig-h3, a novel gene induced in a human adenocarcinoma cell line after treatment with transforming growth factor-beta[J]. DNA Cell Biol, 1992, 11(7): 511-522.
11.	Kim JE, Kim SJ, Lee BH, et al. Identification of motifs for cell adhesion within the repeated domains of transforming growth factor-beta-induced gene, betaig-h3[J]. J Biol Chem, 2000, 275(40): 30907-30915. DOI: 10.1074/jbc.M002752200.
12.	Billings PC, Whitbeck JC, Adams CS, et al. The TGFβ-inducible matrix protein βig-h3 interacts with fibronectin[J]. J Biol Chem, 2002, 277(31): 28003-28009.
13.	Kannabiran C, Sridhar MS, Chakravarthi SK, et al. Genotype-phenotype correlation in 2 Indian families with severe granular corneal dystrophy.[J]. Arch Ophthalmol, 2005, 123(8): 1127-1133.
14.	Ridgway A E, Akhtar S, Munier F L, et al. Ultrastructural and molecular analysis of Bowman’s layer corneal dystrophies: an epithelial origin?[J]. Invest Ophthalmol Vis Sci, 2000, 41(11): 3286-3292.
15.	Weiss JS, Møller HU, Lisch W, et al. The IC3D classification of the corneal dystrophies[J]. Klin Monbl Augenheilkd, 2011, 228 Suppl 1: S1-83. DOI: 10.1055/s-0029-1245895.
16.	Munier FL, Korvatska E, Djemaï A, et al. Kerato-epithelin mutations in four 5q31-linked corneal dystrophies[J]. Nat Genet, 1997, 15(3): 247-51. DOI: 10.1038/ng0397-247.
17.	梁庆丰, 潘志强. 我国TGFBI基因相关性角膜营养不良的研究现状[J]. 国际眼科纵览, 2014, 38(4): 236-241. DOI: 10.3706/atna.j.issn.1673-5803.2014.04.005.Liang QF, Pan ZQ. Current study situation of TGFBI gene related corneal dystrophy in china[J]. Int Rev Ophthalmol, 2014, 38(4): 236-241.DOI: 10.3706/atna.j.issn.1673-5803.2014.04.005.

1. 张承芬, 董方田, 陈有信, 等. 周边视网膜变性[M]//张承芬. 眼底病学. 2版. 北京: 人民卫生出版社, 2010: 543-545.Zhang CF, Dong FT, Chen YX, et al. Peripheral retina lattice degeneration[M]//Zhang CF.Diseases of ocular fundus.2nd.Beijing: People’s Medical Publishing House, 2010: 543-545.
2. Meguro A, Ideta H, Ota M, et al. Common variants in the COL4A4 gene confer susceptibility to lattice degeneration of the retina[J/OL]. PLoS One, 2012, 7(6): 39300 [2012-06-19]. https://doi.org/10.1371/journal.pone.0039300. DOI: 10.1371/journal.pone.0039300.
3. Kocluk Y, Yalniz-Akkaya Z, Burcu A, et al. Corneal topography analysis of stromal corneal dystrophies[J]. Pak J Med Sci, 2015, 31(1): 116-120. DOI: 10.12669/pjms.311.6292.
4. Eifrig DE Jr, Afshari NA, Klintworth GK. The clinical spectrum of granular corneal dystrophy caused by the R124H Mutation in the TGFBI Gene[J]. Invest Ophthalmol Vis Sci, 2004, 45(4): 1516-1530.
5. Kim HS, Yoon SK, Cho BJ, et al. BIGH3 gene mutations and rapid detection in Korean patients with corneal dystrophy[J]. Cornea, 2001, 20(8): 844-849. DOI: 10.1097/00003226-200111000-00013.
6. Evans CJ, Davidson AE, Carnt N, et al. Genotype-phenotype correlation for TGFBI corneal dystrophies identifies p.(G623D) as a novel cause of epithelial basement membrane dystrophy[J]. Invest Ophthalmol Vis Sci, 2016, 57(13): 5407-5414. DOI: 10.1167/iovs.16-19818.
7. Wilson CM, D’Ath PJ, Parmar DN, et al. Keratoconus and granular dystrophy[J/OL]. BMJ Case Rep, 2014, 2014: E1[2014-08-25]. http://casereports.bmj.com/content/2014/bcr-2014-205584.long. DOI: 10.1136/bcr-2014-205584.[publishedonline ahead of print].
8. Boĭko EV, Suetov AA, Mal’tsev DS.Lattice degeneration of the retina[J]. Vestn Oftalmol, 2014, 130(2): 77-82.
9. Yang J, Han X, Huang D, et al. Analysis of TGFBI gene mutations in Chinese patients with corneal dystrophies and review of the literature[J]. Mol Vis, 2010, 16: 1186-1193.
10. Skonier J, Neubauer M, Madisen L, et al. cDNA cloning and sequence analysis of beta ig-h3, a novel gene induced in a human adenocarcinoma cell line after treatment with transforming growth factor-beta[J]. DNA Cell Biol, 1992, 11(7): 511-522.
11. Kim JE, Kim SJ, Lee BH, et al. Identification of motifs for cell adhesion within the repeated domains of transforming growth factor-beta-induced gene, betaig-h3[J]. J Biol Chem, 2000, 275(40): 30907-30915. DOI: 10.1074/jbc.M002752200.
12. Billings PC, Whitbeck JC, Adams CS, et al. The TGFβ-inducible matrix protein βig-h3 interacts with fibronectin[J]. J Biol Chem, 2002, 277(31): 28003-28009.
13. Kannabiran C, Sridhar MS, Chakravarthi SK, et al. Genotype-phenotype correlation in 2 Indian families with severe granular corneal dystrophy.[J]. Arch Ophthalmol, 2005, 123(8): 1127-1133.
14. Ridgway A E, Akhtar S, Munier F L, et al. Ultrastructural and molecular analysis of Bowman’s layer corneal dystrophies: an epithelial origin?[J]. Invest Ophthalmol Vis Sci, 2000, 41(11): 3286-3292.
15. Weiss JS, Møller HU, Lisch W, et al. The IC3D classification of the corneal dystrophies[J]. Klin Monbl Augenheilkd, 2011, 228 Suppl 1: S1-83. DOI: 10.1055/s-0029-1245895.
16. Munier FL, Korvatska E, Djemaï A, et al. Kerato-epithelin mutations in four 5q31-linked corneal dystrophies[J]. Nat Genet, 1997, 15(3): 247-51. DOI: 10.1038/ng0397-247.
17. 梁庆丰, 潘志强. 我国TGFBI基因相关性角膜营养不良的研究现状[J]. 国际眼科纵览, 2014, 38(4): 236-241. DOI: 10.3706/atna.j.issn.1673-5803.2014.04.005.Liang QF, Pan ZQ. Current study situation of TGFBI gene related corneal dystrophy in china[J]. Int Rev Ophthalmol, 2014, 38(4): 236-241.DOI: 10.3706/atna.j.issn.1673-5803.2014.04.005.

Chinese Journal of Ocular Fundus Diseases

Clinical observation and gene mutation detection in a pedigree of retinal lattice degeneration combined with granular corneal dystrophy

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