Abstract
Purpose
To present the phenotypic variability both among and within families in Japanese gelatinous drop-like corneal dystrophy (GDLD), and to study the genetic background of the variability.
Methods
Four Japanese families who suffer from bilateral corneal amyloidoses were studied by a molecular genetic method. All families included a patient whose clinical features alone could not be used to diagnose GDLD. In one family, obvious clinical differences were observed between the two members who were patients. Three families had members who suffered from atypical amyloidoses that had not been initially diagnosed as GDLD. For their final diagnoses and for the investigation of the genetic background of these phenotypes, the sequences of the entire TACSTD2 gene and the genotypes of some polymorphic markers close to the TACSTD2 gene were studied.
Results
Genetic analysis revealed that all the patients possessed a homozygous Q118X mutation in TACSTD2, a major founder mutation in Japanese GDLD. There were no differences in the entire sequence of TACSTD2 in these patients compared with other GDLD patients. Moreover, the genotyping of polymorphic markers near the TACSTD2 gene revealed that these patients shared the same founder chromosome as well as the TACSTD2 gene.
Conclusion
In Japanese GDLD patients, phenotypic variability is observed both among and within families in spite of the allelic homogeneity of Q118X. Even in these atypical cases, the patients shared the same chromosomal region, received from a founder.
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References
Nakaizumi G. A rare case of corneal dystrophy. Acta Soc Ophthalmol Jpn 1914;18:949–950.
Weber FL, Babel J. Gelatinous drop-like dystrophy. A form of primary corneal amyloidosis. Arch Ophthalmol 1980;98:144–148.
Tsujikawa M, Kurahashi H, Tanaka T, et al. Homozygosity mapping of a gene responsible for gelatinous drop-like corneal dystrophy to chromosome 1p. Am J Hum Genet 1998;63:1073–1077.
Tsujikawa M, Kurahashi H, Tanaka T, et al. Identification of the gene responsible for gelatinous drop-like corneal dystrophy. Nat Genet 1999;21:420–423.
Fujiki K, Nakayasu K, Kanai A. Corneal dystrophies in Japan. J Hum Genet 2001;46:431–435.
Yamamoto S, Okada M, Tsujikawa M, et al. The spectrum of beta ig-h3 gene mutations in Japanese patients with corneal dystrophy. Cornea 2000;19:S21–23.
Tsujikawa M, Tsujikawa K, Maeda N, et al. Rapid detection of M1S1 mutations by the protein truncation test. Invest Ophthalmol Vis Sci 2000;41:2466–2468.
Ide T, Nishida K, Maeda N, et al. A spectrum of clinical manifestations of gelatinous drop-like corneal dystrophy in Japan. Am J Ophthalmol 2004;137:1081–1084.
Grimberg J, Nawoschik S, Belluscio L, McKee R, Turck A, Eisenberg A. A simple and efficient non-organic procedure for the isolation of genomic DNA from blood. Nucleic Acids Res 1989; 17:8390.
Munier FL, Korvatska E, Djemai A, et al. Kerato-epithelin mutations in four 5q31-linked corneal dystrophies. Nat Genet 1997;15: 247–251.
Korvatska E, Munier FL, Djemai A, et al. Mutation hot spots in 5q31-linked corneal dystrophies. Am J Hum Genet 1998;62:320–324.
Mashima Y, Imamura Y, Konishi M, et al. Homogeneity of keratoepithelin codon 124 mutations in Japanese patients with either of two types of corneal stromal dystrophy. Am J Hum Genet 1997; 61:1448–1450.
Mashima Y, Yamamoto S, Inoue Y, et al. Association of autosomal dominantly inherited corneal dystrophies with BIGH3 gene mutations in Japan. Am J Ophthalmol 2000;130:516–517.
Konishi M, Yamada M, Nakamura Y, et al. Varied appearance of cornea of patients with corneal dystrophy associated with R124H Mutation in the BIGH3 gene. Cornea 1999;18:424–429
Smolin G. Corneal dystrophies and degenerations. In: Smolin G, Thoft R, editors. Cornea, 3d ed. Boston: Little, Brown; 1994. p. 499–533.
Yoshida S, Kumano Y, Numa S, et al. Two brothers with gelatinous drop-like dystrophy at different stage of the disease; role of mutation analysis. Am J Ophthalmol 2002;13:830–832.
Klintworth GK, Valnickova Z, Kielar RA, Baratz KH, Campbell RJ, Enghild JJ. Familial subepithelial corneal amyloidosis—a lactoferrin-related amyloidosis. Invest Ophthalmol Vis Sci 1997; 38:2756–2763.
Araki-Sasaki K, Ando Y, Nakamura M, et al. Lactoferrin Glu-561Asp facilitates secondary amyloidosis in the cornea. Br J Ophthalmol 2005;89:684–688.
Taniguchi Y, Tsujikawa M, Hibino S, et al. A novel missense mutation in a Japanese patient with gelatinous droplike corneal dystrophy. Am J Ophthalmol 2005;139:186–188.
Kinoshita S, Nishida K, Dota A, et al. Epithelial barrier function and ultrastructure of gelatinous drop-like corneal dystrophy. Cornea 2000;19:551–555.
Kinoshita S, Adachi W, Sotozono C, et al. Characteristics of the human ocular surface epithelium. Prog Retin Eye Res 2001;20: 639–673.
Klintworth GK, Sommer JR, Obrian G, et al. Familial subepithelial corneal amyloidosis (gelatinous drop-like corneal dystrophy): exclusion of linkage to lactoferrin gene. Mol Vis 1998;4:31.
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Tsujikawa, M., Maeda, N., Tsujikawa, K. et al. Chromosomal sharing in atypical cases of gelatinous drop-like corneal dystrophy. Jpn J Ophthalmol 54, 494–498 (2010). https://doi.org/10.1007/s10384-010-0861-6
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DOI: https://doi.org/10.1007/s10384-010-0861-6