A pedigree of Sorsby fundus dystrophy with mutation in TIMP3 gene_Chinese Journal of Ocular Fundus Diseases

Authors：

Yin Xiaofang , Ye Zuke , Tang Xiurong , Liang Yingying , Li Yanhao , Luo Shueke ,  Lu Yan

Institute of Ophthalmology, The Second People’s Hospital of Foshan, Foshan 528000, China;

Corresponding author：

Lu Yan, Email: 837800105@qq.com

Keywords：

Retinal dystrophies; TIMP3 gene; Mutation; Heterozygote

DOI：

10.3760/cma.j.issn.1005-1015.2018.06.005

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

ObjectiveTo observe the clinical manifestation and gene mutation of a pedigree with Sorsby fundus dystrophy (SFD). Methods Ten members in 3 generations of a pedigree with SFD were included in this study. Four patients were observed in the pedigree, including 2 females and 2 males. All 10 members underwent comprehensive ophthalmic examinations, including best-corrected visual acuity, intraocular pressure, slit-lamp biomicroscopy, indirect ophthalmoscopy, fundus color photography and spectral domain optical coherence tomography. Genomic DNA was extracted from peripheral venous blood which was collected from all the members. Relevant exons of ocular diseases were detected by the next generation sequencing method from the proband. The other members underwent Sanger verification. Results Among the four patients, fading eyesight was appeared at their 44, 46, 47 and 40 year-old respectively. The two male patients had bilateral morbidity, and the two female patients had monocular symptoms. DNA sequencing results showed that the proband, other 3 patients and 2 members from the Ⅲ generation had heterozygous mutation of TIMP3 gene in exon 5. The amino acid encoded by TIMP3 gene No.204 codon changed from serine to cysteine (TIMP3:NM_000362:Exon5:c.A610T/p.S204C). CoclusionsThe invasion time of all the patients in this pedigree is after their 40 year-old. Heterozygous mutation at c.610A＞T (p.S204C) in TIMP3 gene is the causative gene of SFD in this pedigree.

Citation： Yin Xiaofang, Ye Zuke, Tang Xiurong, Liang Yingying, Li Yanhao, Luo Shueke, Lu Yan. A pedigree of Sorsby fundus dystrophy with mutation in TIMP3 gene. Chinese Journal of Ocular Fundus Diseases, 2018, 34(6): 546-551. doi: 10.3760/cma.j.issn.1005-1015.2018.06.005 Copy

1.	Capon MR, Polkinghorne PJ, Fitzke FW, et al. Sorsby’s pseudoinflammatory macula dystrophy--sorsby’s fundus dystrophies[J]. Eye, 1988, 2(Pt 1): 114-122. DOI: 10.1038/eye.1988.23.
2.	Sorsby A, Mason ME. A fundus dystrophy with unusual features[J]. Br J Ophthalmol, 1949, 33(2): 67-97.
3.	Hoskin A, Sehmi K, Bird AC. Sorsby’s pseudoinflammatory macular dystrophy[J]. Br J Ophthalmol, 1981, 65(12): 859-865. DOI: 10.1136/bjo.65.12.859.
4.	Hamilton WK, Ewing CC, Ives EJ, et al. Sorsby fundus dystrophy[J].Ophthalmology, 1989, 96(12): 1755-1762. DOI: https://doi.org/10.1016/S0161-6420(89)32647-9.
5.	Gourier HCY, Chong NV. Can novel treatment of age-related macular degeneration be developed by better understanding of Sorsby’s fundus dystrophy[J]. J Clin Med, 2015, 4(5): 874-883. DOI: 10.3390/jcm4050874.
6.	Gemenetzi MK, Luff AJ. Successful treatment of choroidal neovascularization secondary to Sorsby fundus dystrophy with intravitreal bevacizumab[J]. Retin Cases Brief Rep, 2011, 5(2): 132-135. DOI: 10.1097/ICB.0b013e3181cc216b.
7.	Felbor U, Benkwitz C, Klein ML, et al. Sorsby fundus dystrophy: revaluation of variable expressivity in patients carrying a TIMP3 founder mutation[J]. Arch Ophthalmol, 1997, 115(12): 1569-1571. DOI: 10.1001/archopht.1997.01100160739011.
8.	Felbor U, Stöhr H, Amann T, et al. A second independent Tyr168Cys mutation in the tissue inhibitor of metalloproteinases-3(TIMP3) in Sorsby’s fundus dystrophy[J]. J Med Genet, 1996, 33(3): 233-236. DOI: 10.1136/jmg.33.3.233.
9.	Felbor U, Stöhr H, Amann T, et al. A novel Ser156Cys mutation in the tissue inhibitor of metalloproteinases-3(TIMP3) in Sorsby’s fundus dystrophy with unusual clinical features[J]. Hum Mol Genet, 1995, 4(12): 2415-2416.
10.	Jacobson SG, Cideciyan AV, Regunath G, et al. Night blindness in Sorsby’s fundus dystrophy reversed by vitamin A[J]. Nat Genet, 1995, 11(1): 27-32. DOI: 10.1038/ng0995-27.
11.	Tabata Y, Isashiki Y, Kamimura K, et al. A novel splice site mutation in the tissue inhibitor of the metalloproteinases-3 gene in Sorsby’s fundus dystrophy with unusual clinical features[J]. Hum Genet, 1998, 103(2): 179-182.
12.	Bakall B, Sohn EH, Riley J, et al. Novel mutations and change of nomenclature for pathogenic variants in the TIMP3 gene causing Sorsby fundus dystrophy[J]. Invest Ophthalmol Vis Sci, 2014, 55: 3290.
13.	Schoenberger SD, Agarwal A. A novel mutation at the N-terminal domain of the TIMP3 gene in Sorsby fundus dystrophy[J]. Retina, 2013, 33(2): 429-435. DOI: 10.1097/IAE.0b013e318263d3b4.
14.	Saihan Z, Li Z, Rice J, et al. Clinical and biochemical effects of the E139K missense mutation in the TIMP3 gene, associated with Sorsby fundus dystrophy[J]. Mol Vis, 2009, 15: 1218-1230.
15.	Langton KP, McKie N, Curtis A, et al. A novel tissue inhibitor of metalloproteinases-3 mutation reveals a common molecular phenotype in Sorsby’s fundus dystrophy[J]. J Biol Chem, 2000, 275(35): 27027-27031. DOI: 10.1074/jbc.M909677199.
16.	Gliem M, Müller PL, Holz FG, et al. Sorsby fundus dystrophy: novel mutations, novel phenotypic characteristics, and treatment outcomes[J]. Invest Ophthalmol Vis Sci, 2015, 56(4): 2664-2676. DOI: 10.1167/iovs.14-15733.
17.	Lin RJ, Blumenkranz MS, Binkley J, et al. A novel His158Arg mutation in TIMP3 causes a late-onset form of Sorsby fundus dystrophy[J]. Am J Ophthalmol, 2006, 142(5): 839-848. DOI: 10.1016/j.ajo.2006.06.003.
18.	Fung AT, Stöhr H, Weber BHF, et al. Atypical Sorsby fundus dystrophy with a novel Tyr159Cys TIMP-3 mutation[J]. Retin Cases Brief Rep, 2003, 7(1): 71-74. DOI: 10.1097/ICB.0b013e318267101e.
19.	Barbazetto IA, Hayashi M, Klais CM, et al. A novel TIMP3 mutation associated with Sorsby fundus dystrophy[J]. Arch Ophthalmol, 2005, 123(4): 542-543. DOI: 10.1001/archopht.123.4.542.
20.	Jacobson SG, Cideciyan AV, Bennett J, et al. Novel mutation in the TIMP3 gene causes Sorsby fundus dystrophy[J]. Arch Ophthalmol, 2002, 120(3): 376-379. DOI: 10.1001/archopht.120.3.376.
21.	Weber BH, Vogt G, Pruett RC, et al. Mutations in the tissue inhibitor of metalloproteinases-3(TIMP3) in patients with Sorsby’s fundus dystrophy[J]. Nat Genet, 1994, 8(4): 352-356. DOI: 10.1038/ng1294-352.
22.	Weber BHF, Lin B, White K, et al. A mouse model for sorsby fundus dystrophy[J]. Invest Ophthalrnol Vis Sci, 2002, 43(8): 2732-2740.
23.	Atail D, Gregory Evans CY, Louis D, et al. Sorsby fundus dystrophy presenting with choroidal neovascularisation showing good response to steriod treatment[J]. Br J Ophthalmol, 2004, 88(3): 440-441. DOI: 10.1136/bjo.2003.020438.
24.	Holz FG, Haimovici R, Wagner DG, et al. Recurrent choroidal neovascularization after laser photocoagulation in Sorsby’s fundus dystrophy[J]. Retina, 1994, 14(4): 329-334.
25.	Sivaprasad S, Webster AR, Egan CA, et al. Clinical course and treatment outcomes of Sorsby fundus dystrophy[J]. Am J Ophthalmol, 2008, 146(2): 228-234. DOI: 10.1016/j.ajo.2008.03.024.
26.	Peiretti E, Klancnik JM Jr, Spaide RF, et al. Choroidal neovascularization in Sorsby fundus dystrophy treated with photodynamic therapy and intravitreal triamcinolone acetonide[J]. Retina, 2005, 25(3): 377-379. DOI: 10.1097/00006982-200504000-00024.
27.	Menassa N, Burgula S, Empeslidis T, et al. Bilateral choroidal neovascular membrane in a young patient with Sorsby fundus dystrophy: the value of prompt treatment[J/OL]. BMJ Case Rep, 2017, 2017: 220488[2017-08-03]. http://casereports.bmj.com/cgi/pmidlookup?view=long&pmid=28775088. DOI: 10.1136/bcr-2017-220488.
28.	Keller J, Giralt J, Alforja S, et al. Altering the clinical course of Sorsby fundus dystrophy with the use of anti-vascular endothelial growth factor intraocular therapy[J]. Retin Cases Brief Rep, 2015, 9(2): 104-105. DOI: 10.1097/ICB.0000000000000103.

1. Capon MR, Polkinghorne PJ, Fitzke FW, et al. Sorsby’s pseudoinflammatory macula dystrophy--sorsby’s fundus dystrophies[J]. Eye, 1988, 2(Pt 1): 114-122. DOI: 10.1038/eye.1988.23.
2. Sorsby A, Mason ME. A fundus dystrophy with unusual features[J]. Br J Ophthalmol, 1949, 33(2): 67-97.
3. Hoskin A, Sehmi K, Bird AC. Sorsby’s pseudoinflammatory macular dystrophy[J]. Br J Ophthalmol, 1981, 65(12): 859-865. DOI: 10.1136/bjo.65.12.859.
4. Hamilton WK, Ewing CC, Ives EJ, et al. Sorsby fundus dystrophy[J].Ophthalmology, 1989, 96(12): 1755-1762. DOI: https://doi.org/10.1016/S0161-6420(89)32647-9.
5. Gourier HCY, Chong NV. Can novel treatment of age-related macular degeneration be developed by better understanding of Sorsby’s fundus dystrophy[J]. J Clin Med, 2015, 4(5): 874-883. DOI: 10.3390/jcm4050874.
6. Gemenetzi MK, Luff AJ. Successful treatment of choroidal neovascularization secondary to Sorsby fundus dystrophy with intravitreal bevacizumab[J]. Retin Cases Brief Rep, 2011, 5(2): 132-135. DOI: 10.1097/ICB.0b013e3181cc216b.
7. Felbor U, Benkwitz C, Klein ML, et al. Sorsby fundus dystrophy: revaluation of variable expressivity in patients carrying a TIMP3 founder mutation[J]. Arch Ophthalmol, 1997, 115(12): 1569-1571. DOI: 10.1001/archopht.1997.01100160739011.
8. Felbor U, Stöhr H, Amann T, et al. A second independent Tyr168Cys mutation in the tissue inhibitor of metalloproteinases-3(TIMP3) in Sorsby’s fundus dystrophy[J]. J Med Genet, 1996, 33(3): 233-236. DOI: 10.1136/jmg.33.3.233.
9. Felbor U, Stöhr H, Amann T, et al. A novel Ser156Cys mutation in the tissue inhibitor of metalloproteinases-3(TIMP3) in Sorsby’s fundus dystrophy with unusual clinical features[J]. Hum Mol Genet, 1995, 4(12): 2415-2416.
10. Jacobson SG, Cideciyan AV, Regunath G, et al. Night blindness in Sorsby’s fundus dystrophy reversed by vitamin A[J]. Nat Genet, 1995, 11(1): 27-32. DOI: 10.1038/ng0995-27.
11. Tabata Y, Isashiki Y, Kamimura K, et al. A novel splice site mutation in the tissue inhibitor of the metalloproteinases-3 gene in Sorsby’s fundus dystrophy with unusual clinical features[J]. Hum Genet, 1998, 103(2): 179-182.
12. Bakall B, Sohn EH, Riley J, et al. Novel mutations and change of nomenclature for pathogenic variants in the TIMP3 gene causing Sorsby fundus dystrophy[J]. Invest Ophthalmol Vis Sci, 2014, 55: 3290.
13. Schoenberger SD, Agarwal A. A novel mutation at the N-terminal domain of the TIMP3 gene in Sorsby fundus dystrophy[J]. Retina, 2013, 33(2): 429-435. DOI: 10.1097/IAE.0b013e318263d3b4.
14. Saihan Z, Li Z, Rice J, et al. Clinical and biochemical effects of the E139K missense mutation in the TIMP3 gene, associated with Sorsby fundus dystrophy[J]. Mol Vis, 2009, 15: 1218-1230.
15. Langton KP, McKie N, Curtis A, et al. A novel tissue inhibitor of metalloproteinases-3 mutation reveals a common molecular phenotype in Sorsby’s fundus dystrophy[J]. J Biol Chem, 2000, 275(35): 27027-27031. DOI: 10.1074/jbc.M909677199.
16. Gliem M, Müller PL, Holz FG, et al. Sorsby fundus dystrophy: novel mutations, novel phenotypic characteristics, and treatment outcomes[J]. Invest Ophthalmol Vis Sci, 2015, 56(4): 2664-2676. DOI: 10.1167/iovs.14-15733.
17. Lin RJ, Blumenkranz MS, Binkley J, et al. A novel His158Arg mutation in TIMP3 causes a late-onset form of Sorsby fundus dystrophy[J]. Am J Ophthalmol, 2006, 142(5): 839-848. DOI: 10.1016/j.ajo.2006.06.003.
18. Fung AT, Stöhr H, Weber BHF, et al. Atypical Sorsby fundus dystrophy with a novel Tyr159Cys TIMP-3 mutation[J]. Retin Cases Brief Rep, 2003, 7(1): 71-74. DOI: 10.1097/ICB.0b013e318267101e.
19. Barbazetto IA, Hayashi M, Klais CM, et al. A novel TIMP3 mutation associated with Sorsby fundus dystrophy[J]. Arch Ophthalmol, 2005, 123(4): 542-543. DOI: 10.1001/archopht.123.4.542.
20. Jacobson SG, Cideciyan AV, Bennett J, et al. Novel mutation in the TIMP3 gene causes Sorsby fundus dystrophy[J]. Arch Ophthalmol, 2002, 120(3): 376-379. DOI: 10.1001/archopht.120.3.376.
21. Weber BH, Vogt G, Pruett RC, et al. Mutations in the tissue inhibitor of metalloproteinases-3(TIMP3) in patients with Sorsby’s fundus dystrophy[J]. Nat Genet, 1994, 8(4): 352-356. DOI: 10.1038/ng1294-352.
22. Weber BHF, Lin B, White K, et al. A mouse model for sorsby fundus dystrophy[J]. Invest Ophthalrnol Vis Sci, 2002, 43(8): 2732-2740.
23. Atail D, Gregory Evans CY, Louis D, et al. Sorsby fundus dystrophy presenting with choroidal neovascularisation showing good response to steriod treatment[J]. Br J Ophthalmol, 2004, 88(3): 440-441. DOI: 10.1136/bjo.2003.020438.
24. Holz FG, Haimovici R, Wagner DG, et al. Recurrent choroidal neovascularization after laser photocoagulation in Sorsby’s fundus dystrophy[J]. Retina, 1994, 14(4): 329-334.
25. Sivaprasad S, Webster AR, Egan CA, et al. Clinical course and treatment outcomes of Sorsby fundus dystrophy[J]. Am J Ophthalmol, 2008, 146(2): 228-234. DOI: 10.1016/j.ajo.2008.03.024.
26. Peiretti E, Klancnik JM Jr, Spaide RF, et al. Choroidal neovascularization in Sorsby fundus dystrophy treated with photodynamic therapy and intravitreal triamcinolone acetonide[J]. Retina, 2005, 25(3): 377-379. DOI: 10.1097/00006982-200504000-00024.
27. Menassa N, Burgula S, Empeslidis T, et al. Bilateral choroidal neovascular membrane in a young patient with Sorsby fundus dystrophy: the value of prompt treatment[J/OL]. BMJ Case Rep, 2017, 2017: 220488[2017-08-03]. http://casereports.bmj.com/cgi/pmidlookup?view=long&pmid=28775088. DOI: 10.1136/bcr-2017-220488.
28. Keller J, Giralt J, Alforja S, et al. Altering the clinical course of Sorsby fundus dystrophy with the use of anti-vascular endothelial growth factor intraocular therapy[J]. Retin Cases Brief Rep, 2015, 9(2): 104-105. DOI: 10.1097/ICB.0000000000000103.

Previous Article
Novel homozygotic mutation in the NR2E3 gene in a family affected with Goldmann-Favre syndrome
Next Article
Detection and analysis of gene mutation in a case of child’s renal coloboma syndrome

Chinese Journal of Ocular Fundus Diseases

A pedigree of Sorsby fundus dystrophy with mutation in TIMP3 gene

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content