- Email: [email protected]
Gelatino-lattice corneal dystrophy: clinical features and mutational analysis
juvenile stromal dystrophy with homozygous R124H mutation in the keratoepithelin gene in five Japanese patients. Br J Ophthalmol 1998;82:1280 –1284. 3. Fujiki K, Hotta Y, Nakayasu K, Kanai A. Homozygotic patient with ig-h3 gene mutation in granular dystrophy. Cornea 1998;17:288 –292. 4. Okada M, Yamamoto S, Watanabe H, et al. Granular corneal dystrophy with homozygous mutations in the kerato-epithelin gene. Am J Ophthalmol 1998;126:169 –176. 5. Okada M, Yamamoto S, Inoue Y, et al. Severe corneal dystrophy phenotype caused by homozygous R124H keratoepithelin mutations. Invest Ophthalmol Vis Sci 1998;39: 1947–1953.
Gelatino-Lattice Corneal Dystrophy: Clinical Features and Mutational Analysis Takahiro Nakamura, MD, Kohji Nishida, MD, PhD, Atsuyoshi Dota, MS, Wakako Adachi, MD, PhD, Shuji Yamamoto, MD, PhD, Naoyuki Maeda, MD, PhD, Masaki Okada, MD, and Shigeru Kinoshita, MD, PhD PURPOSE:
To report five unrelated Japanese individuals with “gelatino-lattice” corneal dystrophy that clinically resembled, to some extent, gelatinous drop-like corneal dystrophy and lattice corneal dystrophy type 1. METHODS: Genomic DNA isolated from the five individuals with “gelatino-lattice” corneal dystrophy was used as a template for polymerase chain reaction to amplify all exons of the candidate gene ig-h3 and M1S1. The polymerase chain reaction product was then sequenced. RESULTS: In all cases, ig-h3 was mutated in “gelatino-lattice” corneal dystrophy (Arg124Cys), which is the same nucleotide change examined previously in lattice corneal dystrophy type 1. On the other hand, no mutation was detected in the entire coding region of M1S1. CONCLUSION: Based on the results of this study, it is suggested that “gelatino-lattice” corneal dystrophy may be a subtype of lattice corneal dystrophy type 1. (Am J Ophthalmol 2000;129:665– 666. © 2000 by Elsevier Science Inc. All rights reserved.)
Accepted for publication January 10, 2000. From the Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.M., K.N., A.D., W.A., S.K.), and the Department of Ophthalmology, Osaka University Medical School, Osaka, Japan (S.Y., N.M., M.O.). Inquiries to Takahiro Nakamura, MD, Department of Ophthalmology, Kyoto Prefectural University of Medicine, Hirokoji Kawaramachi, Kamigyo-ku, Kyoto 602, Japan; fax: ⫹81-75-251-5663; e-mail: [email protected]
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ATTICE CORNEAL DYSTROPHIES ARE INHERITED, POTEN-
tially blinding, primary, localized corneal amyloidosis. Clinically and histologically, different types of lattice dystrophy exist.1 Type I (MIN 122200), the autosomaldominant form, is characterized by branching stromal lattice figures with subepithelial opacities. On the other hand, gelatinous drop-like corneal dystrophy (MIN 204870) is a rare autosomal recessive disorder characterized by massive subepithelial deposits of amyloid material.2 It was first described by Nakaizumi (1914); most documented cases have been from Japan. We encountered five unrelated Japanese individuals with “gelatino-lattice” corneal dystrophy that clinically resembled, to some extent, gelatinous drop-like corneal dystrophy and lattice corneal dystrophy type 1. However, it is somewhat difficult to distinguish between “gelatino-lattice” corneal dystrophy and gelatinous drop-like corneal dystrophy on the basis of ocular manifestation. Herein, we report on a representative patient, a 33-year-old man referred to our hospital for severe corneal opacities in both eyes. He had had painful recurrent corneal erosions during his teenage years. In his family, the ocular manifestation in his mother and one of his four brothers also resembled that in his eyes, to some extent. Briefly, slit-lamp examination revealed protruding subepithelial masses with a mulberry-like appearance and tiny stromal lattice figures with subepithelial opacities (Figure 1). These subepithelial masses were similar to those of gelatinous drop-like corneal dystrophy; the stromal lattice figures are generally observed in lattice corneal dystrophy type 1. The characteristics of the corneal opacities were similar to those of the other four unrelated patients. In recent years, Munier and associates detected that lattice corneal dystrophy type 1, as well as three other corneal dystrophies that map to 5q31,3 is the result of a mutation in ig-h3.4 According to the latter report, patients with lattice corneal dystrophy type 1 were found to have an Arg124 –⬎Cys mutation caused by a C–⬎T change. Also, Tsujikawa and associates detected that gelatinous drop-like corneal dystrophy is the result of four deleterious mutations in M1S1.5 The mutation most commonly detected was a Glu118 –⬎Stop transition caused by a C–⬎T change. We are unaware of previous reports of “gelatino-lattice” corneal dystrophy and could find no reference to it in a computer search using MEDLINE. Our study was designed to investigate whether ig-h3 and M1S1 are mutated in “gelatino-lattice” corneal dystrophy. With informed consent, we obtained blood from five patients with “gelatino-lattice” corneal dystrophy and 40 healthy volunteers. Genomic DNA was isolated and used as a template for polymerase chain reaction to amplify the entire coding region of ig-h3 and M1S1. The polymerase chain reaction product was then sequenced. Sequencing exon 4 of ig-h3 revealed a C–⬎T transition at nucleotide 417 in “gelatino-lattice” corneal dystrophy, which is the same missense mutation discovered previously in lattice corneal dystrophy type 1.4 Unlike
BRIEF REPORTS
665
FIGURE 1. (Top left) Patient with “gelatino-lattice” corneal dystrophy demonstrates protruding subepithelial masses with a mulberry-like appearance, in addition to tiny branching stromal lattice figures with subepithelial opacities. (Top right) Same patient with “gelatino-lattice” corneal dystrophy cornea under scleral scattering illumination. (Bottom left) Patient with lattice corneal dystrophy type 1 demonstrates fine lattice lines with subepithelial opacities. (Bottom right) Patient with gelatinous drop-like corneal dystrophy demonstrates subepithelial amyloid that forms raised lesions with mulberry-like appearance.
ig-h3, however, no mutation was detected in the entire coding region of M1S1 (Figure 2). Although the cause of “gelatino-lattice” corneal dystrophy has not been demonstrated clearly, it appears that the five individuals had the same genotype as lattice corneal dystrophy type 1, indicating that “gelatino-lattice” corneal dystrophy is a subtype of lattice corneal dystrophy type 1. REFERENCES
1. Klintworth GK. Lattice corneal dystrophy: an inherited variety of amyloidosis restricted to the cornea. Am J Pathol 1967;50:371–399. 2. Nagataki S, Tanishima T, Sakamoto T, et al. A case of primary gelatinous drop-like corneal dystrophy. Jpn J Ophthalmol 1972;16:107–116. 3. Stone EM, Mathers WD, Rosenwasser GOD, et al. Three autosomal dominant corneal dystrophies map to chromosome 5q. Nat Genet 1994;6:47–51. 4. Munier FL, Korvatska E, Djemai A, et al. Kerato-epithelin mutations in four 5q31-linked corneal dystrophies. Nat Genet 1997;15:247–251. 5. Tsujikawa M, Kurahashi H, Tanaka T, et al. Identification of the gene responsible for gelatinous drop-like corneal dystrophy. Nat Genet 1999;21:420 – 424.
FIGURE 2. (Left) Sequence analysis of exon 4 of ig-h3 in region codon 124. Arrows indicate mutation Arg124Cys. (Right) Sequence analysis of M1S1 in region codon 118. Arrows indicate mutation Glu118Stop. No mutation was detected in “gelatino-lattice” corneal dystrophy.
666
AMERICAN JOURNAL
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OPHTHALMOLOGY
MAY 2000
Gelatino-Lattice Corneal Dystrophy: Clinical Features and Mutational Analysis Takahiro Nakamura, MD, Kohji Nishida, MD, PhD, Atsuyoshi Dota, MS, Wakako Adachi, MD, PhD, Shuji Yamamoto, MD, PhD, Naoyuki Maeda, MD, PhD, Masaki Okada, MD, and Shigeru Kinoshita, MD, PhD PURPOSE:
To report five unrelated Japanese individuals with “gelatino-lattice” corneal dystrophy that clinically resembled, to some extent, gelatinous drop-like corneal dystrophy and lattice corneal dystrophy type 1. METHODS: Genomic DNA isolated from the five individuals with “gelatino-lattice” corneal dystrophy was used as a template for polymerase chain reaction to amplify all exons of the candidate gene ig-h3 and M1S1. The polymerase chain reaction product was then sequenced. RESULTS: In all cases, ig-h3 was mutated in “gelatino-lattice” corneal dystrophy (Arg124Cys), which is the same nucleotide change examined previously in lattice corneal dystrophy type 1. On the other hand, no mutation was detected in the entire coding region of M1S1. CONCLUSION: Based on the results of this study, it is suggested that “gelatino-lattice” corneal dystrophy may be a subtype of lattice corneal dystrophy type 1. (Am J Ophthalmol 2000;129:665– 666. © 2000 by Elsevier Science Inc. All rights reserved.)
Accepted for publication January 10, 2000. From the Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.M., K.N., A.D., W.A., S.K.), and the Department of Ophthalmology, Osaka University Medical School, Osaka, Japan (S.Y., N.M., M.O.). Inquiries to Takahiro Nakamura, MD, Department of Ophthalmology, Kyoto Prefectural University of Medicine, Hirokoji Kawaramachi, Kamigyo-ku, Kyoto 602, Japan; fax: ⫹81-75-251-5663; e-mail: [email protected]
VOL. 129, NO. 5
L
ATTICE CORNEAL DYSTROPHIES ARE INHERITED, POTEN-
tially blinding, primary, localized corneal amyloidosis. Clinically and histologically, different types of lattice dystrophy exist.1 Type I (MIN 122200), the autosomaldominant form, is characterized by branching stromal lattice figures with subepithelial opacities. On the other hand, gelatinous drop-like corneal dystrophy (MIN 204870) is a rare autosomal recessive disorder characterized by massive subepithelial deposits of amyloid material.2 It was first described by Nakaizumi (1914); most documented cases have been from Japan. We encountered five unrelated Japanese individuals with “gelatino-lattice” corneal dystrophy that clinically resembled, to some extent, gelatinous drop-like corneal dystrophy and lattice corneal dystrophy type 1. However, it is somewhat difficult to distinguish between “gelatino-lattice” corneal dystrophy and gelatinous drop-like corneal dystrophy on the basis of ocular manifestation. Herein, we report on a representative patient, a 33-year-old man referred to our hospital for severe corneal opacities in both eyes. He had had painful recurrent corneal erosions during his teenage years. In his family, the ocular manifestation in his mother and one of his four brothers also resembled that in his eyes, to some extent. Briefly, slit-lamp examination revealed protruding subepithelial masses with a mulberry-like appearance and tiny stromal lattice figures with subepithelial opacities (Figure 1). These subepithelial masses were similar to those of gelatinous drop-like corneal dystrophy; the stromal lattice figures are generally observed in lattice corneal dystrophy type 1. The characteristics of the corneal opacities were similar to those of the other four unrelated patients. In recent years, Munier and associates detected that lattice corneal dystrophy type 1, as well as three other corneal dystrophies that map to 5q31,3 is the result of a mutation in ig-h3.4 According to the latter report, patients with lattice corneal dystrophy type 1 were found to have an Arg124 –⬎Cys mutation caused by a C–⬎T change. Also, Tsujikawa and associates detected that gelatinous drop-like corneal dystrophy is the result of four deleterious mutations in M1S1.5 The mutation most commonly detected was a Glu118 –⬎Stop transition caused by a C–⬎T change. We are unaware of previous reports of “gelatino-lattice” corneal dystrophy and could find no reference to it in a computer search using MEDLINE. Our study was designed to investigate whether ig-h3 and M1S1 are mutated in “gelatino-lattice” corneal dystrophy. With informed consent, we obtained blood from five patients with “gelatino-lattice” corneal dystrophy and 40 healthy volunteers. Genomic DNA was isolated and used as a template for polymerase chain reaction to amplify the entire coding region of ig-h3 and M1S1. The polymerase chain reaction product was then sequenced. Sequencing exon 4 of ig-h3 revealed a C–⬎T transition at nucleotide 417 in “gelatino-lattice” corneal dystrophy, which is the same missense mutation discovered previously in lattice corneal dystrophy type 1.4 Unlike
BRIEF REPORTS
665
FIGURE 1. (Top left) Patient with “gelatino-lattice” corneal dystrophy demonstrates protruding subepithelial masses with a mulberry-like appearance, in addition to tiny branching stromal lattice figures with subepithelial opacities. (Top right) Same patient with “gelatino-lattice” corneal dystrophy cornea under scleral scattering illumination. (Bottom left) Patient with lattice corneal dystrophy type 1 demonstrates fine lattice lines with subepithelial opacities. (Bottom right) Patient with gelatinous drop-like corneal dystrophy demonstrates subepithelial amyloid that forms raised lesions with mulberry-like appearance.
ig-h3, however, no mutation was detected in the entire coding region of M1S1 (Figure 2). Although the cause of “gelatino-lattice” corneal dystrophy has not been demonstrated clearly, it appears that the five individuals had the same genotype as lattice corneal dystrophy type 1, indicating that “gelatino-lattice” corneal dystrophy is a subtype of lattice corneal dystrophy type 1. REFERENCES
1. Klintworth GK. Lattice corneal dystrophy: an inherited variety of amyloidosis restricted to the cornea. Am J Pathol 1967;50:371–399. 2. Nagataki S, Tanishima T, Sakamoto T, et al. A case of primary gelatinous drop-like corneal dystrophy. Jpn J Ophthalmol 1972;16:107–116. 3. Stone EM, Mathers WD, Rosenwasser GOD, et al. Three autosomal dominant corneal dystrophies map to chromosome 5q. Nat Genet 1994;6:47–51. 4. Munier FL, Korvatska E, Djemai A, et al. Kerato-epithelin mutations in four 5q31-linked corneal dystrophies. Nat Genet 1997;15:247–251. 5. Tsujikawa M, Kurahashi H, Tanaka T, et al. Identification of the gene responsible for gelatinous drop-like corneal dystrophy. Nat Genet 1999;21:420 – 424.
FIGURE 2. (Left) Sequence analysis of exon 4 of ig-h3 in region codon 124. Arrows indicate mutation Arg124Cys. (Right) Sequence analysis of M1S1 in region codon 118. Arrows indicate mutation Glu118Stop. No mutation was detected in “gelatino-lattice” corneal dystrophy.
666
AMERICAN JOURNAL
OF
OPHTHALMOLOGY
MAY 2000