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 CenterNone of the authors have financial or proprietary interests in any material or method mentioned in this study.
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.
DNA Nucleotide change
Protein Amino Acid change
Reference
c.967delT p.Ser323LeufsX5 Bredrup et al.
c.941delC p.Pro314HisfsX14 Rodahl et al.
Congenital HereditaryStromal Dystrophy (CHSD)
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.
Only 4 families with CHSD were reported.
The decorin gene (DCN) was identified
as a causative gene of CHSD in 2005.
Decorin
Class I family ofsmall 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
Gene Symbol Chromosomal locus
DCN 12q21.33
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
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
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 incisionsPOD
7 months
2148 cell/mm2
Results : Pathologic findings
A few focal infiltration of neutrophils
Normal keratocyte Normal collagen lamellae
Thin collagen fibril in
electron-lucent background layer
Results : Case 2
Thin collagen fibril in electron-lucent background layer
F/1corneal opacities in her both eyes after birth
V 20/150 OD 20/150 OS (Teller Visual Acuity)
OSOD
POD 7 years
Bilateral Penetrating keratoplasty
Results : DNA analysis
The proband
: c.947delG
(p.Gly316AspfsX12)
The proband’s son
(no clinical manifestation)
: normal
The proband’s daughter
: c.947delG
(p.Gly316AspfsX12)
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
References
1. 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):115-25.7. 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):804-8.8. 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):809-13.9. 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.