20대 한국인에서 관찰되는 제2형 과립각막이상증의 다양한 표현형에 대한 고찰
Phenotypes of Granular Corneal Dystrophy Type 2 among Koreans in Their Twenties
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
목적: 제2형 과립각막이상증(granular corneal dystrophy type 2, GCD2)은 각막에 과립 및 격자형 침착물이 생기는 유전 질환으로, 동형접합자와 이형접합자가 있다. GCD2는 중심각막수술 후 악화되며, 이형접합자의 표현형에 개인차가 보고되는 바, 굴절수술이 잦은 국내 20대에서 관찰된 다양한 표현형을 조사하였다. 대상과 방법: 유전자(transforming growth factor β induced gene)검사 결과 R124H 변이가 발견되어 GCD2로 진단된 20대 환자 중동형접합자 1인, 복합이형접합자 1인, 단순 이형접합자임에도 과립형 참착물이 나이에 비하여 많은 1인, 보편적인 표현형의 이형접합자 1인, 각막에 초기 증상인 과립형 침착물이 보이지 않는 이형접합자 4인의 각막을 세극등현미경으로 관찰 및 촬영하였다. 결과: 동형접합자는 각막을 뒤덮는 융합성의 과립침착물을 보였다. 복합이형접합자의 경우 중심각막을 대부분 덮는 과립형과 격자형각막혼탁을 보였다. 단순 이형접합자임에도 단안에 30개 내외의 과립형 침착물이 존재하는 경우도 있었다. 투명각막으로 판정받았던이형접합자 4인 중에서 1인은 6개월 뒤 단안에 미세한 1개의 병변을, 1인은 3주 뒤 재검 시 단안에 매우 희미한 의심 병변 1개를 보였으며, 2인은 1회 조사 후에 투명각막으로 판정하였다. 결론: 20대의 GCD2 환자에서, 매우 혼탁한 각막부터 거의 투명한 경우까지 다양한 표현형이 나타남을 확인하였다. 병변 발견이 힘든GCD2 각막이 존재하므로 각막 중심부 수술 전 세심한 관찰과 검사가 필요하다.
Abstract
Purpose: Granular corneal dystrophy type 2 (GCD2) is a hereditary disease that features granular and lattice stromal deposits in the cornea. There are homozygotes and heterozygotes and the opacities are exacerbated by corneal trauma or surgery, such as laser in situ keratomileusis (LASIK). As there is individual variability in GCD2 phenotypes, we investigated various corneal features of GCD2 patients in their twenties, the main age group for refractive surgery. Methods: From genetically confirmed GCD2 patients who had an R124H mutation of the transforming growth factor β induced (TGFBI) gene at age 20 to 29 years, we chose representative patients: one homozygote; one compound heterozygote; one simple heterozygote with a severe phenotype with many granular deposits; one common heterozygote; and four heterozygotes with normal corneas. The corneas of all patients were subject to slit-lamp examination and photographed. Results: The homozygote had confluent granular deposits covering the cornea. The compound heterozygote had granular and lattice deposits covering the center of the cornea. The patient with a severe phenotype had more than 30 granular deposits in one eye, but was a simple GCD2 heterozygote, verified by full-sequencing of the TGFBI gene. In the four patients with normal corneas, a single small lesion was subsequently detected during follow-up in two, at 3 weeks and 6 months, respectively. Both corneas were judged clear at chance examinations. Conclusions: Among Koreans in their twenties, GCD2 patients have various phenotypes, from clear corneas to severe confluent opacities. There are GCD2 heterozygotes with nearly clear corneas, so caution must be taken when choosing patients for refractive surgery.
참고문헌 (29)
- 정소향, "아벨리노각막이상증으로 진단된 한국인 환자의 각막병변의 분류 및 임상양상", 대한안과학회지, 46(6), pp.938~944 (2005), 대한안과학회
- Han KE, "Extremely varied phenotypes in granular corneal dystrophy type 2 heterozygotes", Mol Vis, 18, pp.1755~1762 (2012)
- Han KE, "Clinical findings and treatments of granular corneal dystrophy type 2(avellino corneal dystrophy) : a review of the literature", Eye Contact Lens, 36, pp.296~299 (2010)
- Kheir V, "Mutation update : TGFBI pathogenic and likely pathogenic variants in corneal dystrophies", Hum Mutat, 40, pp.675~693 (2019)
- Munier FL, "Kerato-epithelin mutations in four 5q31-linked corneal dystrophies", Nat Genet, 15, pp.247~251 (1997)
- Streeten BW, "Immunolocalization of beta IG-H3 protein in 5q31-linked corneal dystrophies and normal corneas", Arch Ophthalmol, 117, pp.67~75 (1999)
- Lee JH, "Prevalence of granular corneal dystrophy type 2(Avellino corneal dystrophy)in the Korean population", Ophthalmic Epidemiol, 17, pp.160~165 (2010)
- Park JE, "Prevalence of granular corneal dystrophy type 2-related TGFBI p.R124H variant in a South Korean population", Mol Vis, 27, pp.283~287 (2021)
- Moon JW, "Homozygous granular corneal dystrophy type II(Avellino corneal dystrophy) : natural history and progression after treatment", Cornea, 26, pp.1095~1100 (2007)
- Diaper CJ, "Clinical and immunopathological corneal phenotype in homozygotes for the BIGH3 R124H mutation", Eye(Lond), 19, pp.92~96 (2005)
- Holland EJ, "Avellino corneal dystrophy. Clinical manifestations and natural history", Ophthalmology, 99, pp.1564~1568 (1992)
- Kim SW, "Characteristic features of granular deposit formation in granular corneal dystrophy type 2", Cornea, 30, pp.848~854 (2011)
- Jun I, "Compound heterozygous mutations in TGFBI cause a severe phenotype of granular corneal dystrophy type 2", Sci Rep, 11, pp.6986~ (2021)
- 송주선, "Mutation Analysis of the TGFBI Gene in Consecutive Korean Patients With Corneal Dystrophies", Annals of Laboratory Medicine, 35(3), pp.336~340 (2015), 대한진단검사의학회
- Yam GH, "In vitro amyloid aggregate forming ability of TGFBI mutants that cause corneal dystrophies", Invest Ophthalmol Vis Sci, 53, pp.5890~5898 (2012)
- Yamada N, "Double mutation(R124H, N544S)of TGFBI in two sisters with combined expression of Avellino and lattice corneal dystrophies", Mol Vis, 15, pp.974~979 (2009)
- Roh MI, "Avellino corneal dystrophy exacerbated after LASIK : scanning electron microscopic findings", Cornea, 25, pp.306~311 (2006)
- Banning CS, "Exacerbation of Avellino corneal dystrophy after LASIK in North America", Cornea, 25, pp.482~484 (2006)
- Jun RM, "Avellino corneal dystrophy after LASIK", Ophthalmology, 111, pp.463~468 (2004)
- Choi SI, "Impaired autophagy and delayed autophagic clearance of transforming growth factor β-induced protein(TGFBI)in granular corneal dystrophy type 2", Autophagy, 8, pp.1782~1797 (2012)
- Kim TI, "Altered mitochondrial function in type 2 granular corneal dystrophy", Am J Pathol, 179, pp.684~692 (2011)
- Choi SI, "Lysosomal dysfunction of corneal fibroblasts underlies the pathogenesis of granular corneal dystrophy type 2 and can be rescued by TFEB", J Cell Mol Med, 24, pp.10343~10355 (2020)
- Choi SI, "Involvement of TGF-{beta} receptor-and integrin-mediated signaling pathways in the pathogenesis of granular corneal dystrophy II", Invest Ophthalmol Vis Sci, 51, pp.1832~1847 (2010)
- Rapuano CJ, "Phototherapeutic keratectomy : who are the best candidates and how do you treat them?", Curr Opin Ophthalmol, 21, pp.280~282 (2010)
- Jung SH, "Phototherapeutic keratectomy in diffuse stromal haze in granular corneal dystrophy type 2", Cornea, 32, pp.296~300 (2013)
- Dinh R, "Recurrence of corneal dystrophy after excimer laser phototherapeutic keratectomy", Ophthalmology, 106, pp.1490~1497 (1999)
- Inoue T, "Recurrence of corneal dystrophy resulting from an R124H Big-h3 mutation after phototherapeutic keratectomy", Cornea, 21, pp.570~573 (2002)
- Kim JW, "Phenotypic non-penetrance in granular corneal dystrophy type II", Graefes Arch Clin Exp Ophthalmol, 246, pp.1629~1631 (2008)
- Cao W, "Reduced penetrance in familial Avellino corneal dystrophy associated with TGFBI mutations", Mol Vis, 15, pp.70~75 (2009)