1 / 12

Jae-hyung Kim, MD 1 Jung Min Ko, MD 2 Inchul Lee, MD 3 Jooeun Lee, MD 1 Jae Yong Kim, MD 1

A Novel Mutation of the decorin gene identified in a Korean family with congenital hereditary stromal dystrophy. Jae-hyung Kim, MD 1 Jung Min Ko, MD 2 Inchul Lee, MD 3 Jooeun Lee, MD 1 Jae Yong Kim, MD 1 Myoung Joon Kim, MD 1 Hungwon Tchah, MD 1

delu
Download Presentation

Jae-hyung Kim, MD 1 Jung Min Ko, MD 2 Inchul Lee, MD 3 Jooeun Lee, MD 1 Jae Yong Kim, MD 1

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. A Novel Mutation ofthe decorin gene identified in a Korean family with congenital hereditary stromal dystrophy Jae-hyung Kim, MD1 Jung Min Ko, MD2 Inchul Lee, MD3 Jooeun Lee, MD1 Jae Yong Kim, MD1 Myoung Joon Kim, MD1 Hungwon Tchah, MD1 1Department of Ophthalmology, University of Ulsan College of Medicine, Asan Medical Center 2Department of Medical genetics, College of Medicine, Ajoo University 3Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center None of the authors have financial or proprietary interests in any material or method mentioned in this study.

  2. Congenital HereditaryStromal Dystrophy (CHSD) : Congenital, autosomal dominant inherited bilateral, non-progressive, diffuse flaky lesions in the central anterior stroma, which may involve the posterior stroma Transmission electron microscopy (TEM) : normal lamellae of collagen fibrils separated by abnormal collagen fibrils which were haphazardly arranged in the electron-lucent background layers Bredrup C, Knappskog PM, Majewski J, et al. Congenital stromal dystrophy of the cornea caused by a mutation in the decorin gene. Invest Ophthalmol Vis Sci 2005;46(2):420-6.

  3. Congenital HereditaryStromal Dystrophy (CHSD) Only 4 families with CHSD were reported. The decorin gene (DCN) was identified as a causative gene of CHSD in 2005. Bredrup C, Knappskog PM, Majewski J, et al. Invest Ophthalmol Vis Sci 2005;46(2):420-6. Rodahl E, Van Ginderdeuren R, Knappskog PM, et al. Am J Ophthalmol 2006;142(3):520-1.

  4. Decorin Class I family of small leucine-rich repeat proteoglycan (SLRP) Function - Formation and/or organization of collagen fibrils - Modulation of cell adhesion, angiogenesis, cell matrix formation - Modulation of the activity of growth factors (TGF-β) - TGF-β-independent effects on cell proliferation and behavior

  5. Patients and Methods Ophthalmic examination Slit lamp examination Best corrected visual acuity (BCVA) Anterior segment optical coherent tomography (OCT, Visante OCT, Carl Zeiss Meditec Inc., Dublin, CA) Confocal microscopy (ConfoScan 4, Nidek Technologies, Padova, Italy) Pathologic examination Hematoxylin and eosin (H&E) Masson’s Trichrome Alcian blue Congo Red Periodic acid stain (PAS Transmission electron microscopy (TEM) DNA analysis

  6. Results : Case Reports F/29 corneal opacities in her both eyes from her childhood the same symptom in her daughter from birth MR -3.0D -0.75D X 30˚ (20/25) -2.0D -1.5D X 150˚ (20/32) Intraocular pressure : 17 mmHg OD 19mmHg OS

  7. Results : Case 1 Deep anterior lamellar keratoplasty (DALK) using a big-bubble technique and a 60 kHz femtosecond laser (IntraLase™, Abbott Medical Optics, Irvine, CA) for zigzag-shaped incisions POD 7 months 2148 cell/mm2

  8. Results : Pathologic findings Thin collagen fibril in electron-lucent background layer A few focal infiltration of neutrophils Normal keratocyte Normal collagen lamellae

  9. Results : Case 2 F/1 corneal opacities in her both eyes after birth V 20/150 OD 20/150 OS (Teller Visual Acuity) Thin collagen fibril in electron-lucent background layer Bilateral Penetrating keratoplasty OS OD POD 7 years

  10. Results : DNA analysis The proband : c.947delG (p.Gly316AspfsX12) The proband’s daughter : c.947delG (p.Gly316AspfsX12) The proband’s son (no clinical manifestation) : normal

  11. Conclusions • Congenital Hereditary Stromal Dystrophy in a Korean family • : the 3rd family confirmed by DNA analysis in the world • A novel frameshift mutation : c.947delG (p.Gly316AspfsX12) • : Premature truncated protein lacking 33 amino acid C-terminal • - Residues within the ear repeat in C-terminal • related to functional specialization • Premature truncation in C-terminal might disturb ligand bindings • The DCN gene can be a major causing gene of CHSD

  12. References • De Sousa LB, Mannis MJ. The Stromal Dystrophies. In: Krachmer JH, Mannis MJ, Holland EJ, eds. • Cornea, 2nd ed. Philadelphia: Mosby, 2005. • 2. Van Ginderdeuren R, De Vos R, Casteels I, Foets B. Report of a new family with dominant • congenital heredity stromal dystrophy of the cornea. Cornea 2002;21(1):118-20. • 3. Rodahl E, Van Ginderdeuren R, Knappskog PM, et al. A second decorin frame shift mutation in a • family with congenital stromal corneal dystrophy. Am J Ophthalmol 2006;142(3):520-1. • 4. Bredrup C, Knappskog PM, Majewski J, et al. Congenital stromal dystrophy of the cornea caused by • a mutation in the decorin gene. Invest Ophthalmol Vis Sci 2005;46(2):420-6. • 5. Witschel H, Fine BS, Grutzner P, McTigue JW. Congenital hereditary stromal dystrophy of the • cornea. Arch Ophthalmol 1978;96(6):1043-51. • 6. Pouliquen Y, Lacombe E, Schreinzer C, et al. [Familial congenital dystrophy of the corneal stroma: • Turpin's syndrome (author's transl)]. J Fr Ophtalmol 1979;2(2):115-25. • Price FW, Jr., Price MO, Grandin JC, Kwon R. Deep anterior lamellar keratoplasty with • femtosecond-laser zigzag incisions. J Cataract Refract Surg 2009;35(5):804-8. • Farid M, Steinert RF. Deep anterior lamellar keratoplasty performed with the femtosecond laser • zigzag incision for the treatment of stromal corneal pathology and ectatic disease. J Cataract • Refract Surg 2009;35(5):809-13. • Turpin R, Tisserand M, Serane J. Opacites corneennes hereditaires et congenitales reparties sur • trois generations et atteignant deux jumelles monozygotes. Arch Ophthalmol 1939;3:109-11. • 10. Odland M. Dystrophia corneae parenchymatosa congenita. A clinical, morphological • and histochemical examination. Acta Ophthalmol (Copenh) 1968;46(3):477-85. • 11. Beuerman RW. Tear film. In: Krachmer JH, Mannis MJ, Holland EJ, eds. • Cornea, 2nd ed. Philadelphia: Mosby, 2005. • 12. Anderson JA, Murphy JA, Gaster RN. Inflammatory cell responses • to radial keratotomy. Refract Corneal Surg 1989;5(1):21-6. • 13. Iozzo RV. The biology of the small leucine-rich proteoglycans. Functional • network of interactive proteins. J Biol Chem 1999;274(27):18843-6. • 14. Michelacci YM. Collagens and proteoglycans of the corneal extracellular matrix. • Braz J Med Biol Res 2003;36(8):1037-46.

More Related