Skip to main content
NCBI home page
The British Journal of Ophthalmology logoLink to The British Journal of Ophthalmology
. 2000 Jun;84(6):583–585. doi: 10.1136/bjo.84.6.583

Corneal amyloidosis caused by Leu518Pro mutation of βig-h3 gene

K Hirano 1, Y Hotta 1, K Fujiki 1, A Kanai 1
PMCID: PMC1723504  PMID: 10837380

Abstract

AIM—To report a Japanese family diagnosed clinically as having lattice corneal dystrophy type I (LCDI) in which a Leu518Pro mutation in the βig-h3 gene and not the R124C mutation reported previously was found.
METHODS—Molecular genetic analysis was performed on DNA extracted from peripheral leucocytes from four members (three affected and one unaffected) of a family. Exon 4 of the βig-h3 gene was amplified by PCR and directly sequenced. Histopathological study was performed on the corneal tissue from the proband obtained during deep lamellar keratoplasty.
RESULTS—All the affected members were clinically diagnosed as having LCDI, and the pedigree indicated an autosomal dominant inheritance. A heterozygous single base pair transition (CTG to CCG, leucine to proline) was detected in codon 518 of the βig-h3 gene in the three affected members, and not in the unaffected member. No mutation was found in codon 124. Amyloid deposits were observed between the collagen bundles of the corneal stroma and were seen to extend deep into the stroma.
CONCLUSION—The Leu518Pro mutated βig-h3 forms amyloidogeneic intermediates which precipitate in the cornea and gives rise to a clinical appearance of LCDI. 



Full Text

The Full Text of this article is available as a PDF (185.4 KB).

Figure 1  .

Figure 1  

Open in a new tab

Pedigree of the family. The arrow indicates the proband (III-4). III-7 and 8 are fraternal twin sisters.

Figure 2  .

Figure 2  

Open in a new tab

Slit lamp biomicroscopic findings. (a) The proband (III-4). Refractile lattice lines (arrows) are seen in the mid-peripheral area of the cornea. Inset shows the central corneal opacity. (b) Patient IV-1. Subepithelial white dots and placoid pattern of corneal opacity are seen in the inset. Refractile fine lines (arrows) can be seen.

Figure 3  .

Figure 3  

Open in a new tab

Nucleotide sequences of the βig-h3 gene using sense primer. Three affected individuals (III-2, III-4, IV-1) show a heterozygous single base pair transition (CTG to CCG, Leu to Pro). The proband's unaffected sister (III-7) shows wild type allele.

Figure 4  .

Figure 4  

Open in a new tab

Histological appearance of the proband's cornea stained with congo red. (a) The epithelium varies in thickness and the interruption of Bowman's layer can be seen (arrowheads). Pink to orange coloured amyloid deposits (arrows) are seen among the bundles of the collagen fibrils. These deposits demonstrate green birefringence with a polarising filter (b, arrows) (bar =100 µm).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Endo S., Nguyen T. H., Fujiki K., Hotta Y., Nakayasu K., Yamaguchi T., Ishida N., Kanai A. Leu518Pro mutation of the beta ig-h3 gene causes lattice corneal dystrophy type I. Am J Ophthalmol. 1999 Jul;128(1):104–106. doi: 10.1016/s0002-9394(99)00053-7. [DOI] [PubMed] [Google Scholar]
  2. Fujiki K., Hotta Y., Nakayasu K., Yokoyama T., Takano T., Yamaguchi T., Kanai A. A new L527R mutation of the betaIGH3 gene in patients with lattice corneal dystrophy with deep stromal opacities. Hum Genet. 1998 Sep;103(3):286–289. doi: 10.1007/s004390050818. [DOI] [PubMed] [Google Scholar]
  3. Hotta Y., Fujiki K., Ono K., Fujimaki T., Nakayasu K., Yamaguchi T., Kanai A. Arg124Cys mutation of the betaig-h3 bene in a Japanese family with lattice corneal dystrophy type I. Jpn J Ophthalmol. 1998 Nov-Dec;42(6):450–455. doi: 10.1016/s0021-5155(98)00050-1. [DOI] [PubMed] [Google Scholar]
  4. Korvatska E., Munier F. L., Zografos L., Ahmad F., Faggioni R., Dolivo-Beuret A., Uffer S., Pescia G., Schorderet D. F. Delineation of a 1-cM region on distal 5q containing the locus for corneal dystrophies Groenouw type I and lattice type I and exclusion of the candidate genes SPARC and LOX. Eur J Hum Genet. 1996;4(4):214–218. doi: 10.1159/000472201. [DOI] [PubMed] [Google Scholar]
  5. Munier F. L., Korvatska E., Djemaï A., Le Paslier D., Zografos L., Pescia G., Schorderet D. F. Kerato-epithelin mutations in four 5q31-linked corneal dystrophies. Nat Genet. 1997 Mar;15(3):247–251. doi: 10.1038/ng0397-247. [DOI] [PubMed] [Google Scholar]
  6. Okada M., Yamamoto S., Tsujikawa M., Watanabe H., Inoue Y., Maeda N., Shimomura Y., Nishida K., Quantock A. J., Kinoshita S. Two distinct kerato-epithelin mutations in Reis-Bücklers corneal dystrophy. Am J Ophthalmol. 1998 Oct;126(4):535–542. doi: 10.1016/s0002-9394(98)00135-4. [DOI] [PubMed] [Google Scholar]
  7. Small K. W., Mullen L., Barletta J., Graham K., Glasgow B., Stern G., Yee R. Mapping of Reis-Bücklers' corneal dystrophy to chromosome 5q. Am J Ophthalmol. 1996 Apr;121(4):384–390. doi: 10.1016/s0002-9394(14)70434-9. [DOI] [PubMed] [Google Scholar]
  8. Stewart H. S., Ridgway A. E., Dixon M. J., Bonshek R., Parveen R., Black G. Heterogeneity in granular corneal dystrophy: identification of three causative mutations in the TGFBI (BIGH3) gene-lessons for corneal amyloidogenesis. Hum Mutat. 1999;14(2):126–132. doi: 10.1002/(SICI)1098-1004(1999)14:2<126::AID-HUMU4>3.0.CO;2-W. [DOI] [PubMed] [Google Scholar]
  9. Stewart H., Black G. C., Donnai D., Bonshek R. E., McCarthy J., Morgan S., Dixon M. J., Ridgway A. A. A mutation within exon 14 of the TGFBI (BIGH3) gene on chromosome 5q31 causes an asymmetric, late-onset form of lattice corneal dystrophy. Ophthalmology. 1999 May;106(5):964–970. doi: 10.1016/S0161-6420(99)00539-4. [DOI] [PubMed] [Google Scholar]
  10. Stone E. M., Mathers W. D., Rosenwasser G. O., Holland E. J., Folberg R., Krachmer J. H., Nichols B. E., Gorevic P. D., Taylor C. M., Streb L. M. Three autosomal dominant corneal dystrophies map to chromosome 5q. Nat Genet. 1994 Jan;6(1):47–51. doi: 10.1038/ng0194-47. [DOI] [PubMed] [Google Scholar]
  11. Streeten B. W., Qi Y., Klintworth G. K., Eagle R. C., Jr, Strauss J. A., Bennett K. Immunolocalization of beta ig-h3 protein in 5q31-linked corneal dystrophies and normal corneas. Arch Ophthalmol. 1999 Jan;117(1):67–75. doi: 10.1001/archopht.117.1.67. [DOI] [PubMed] [Google Scholar]
  12. Yamamoto S., Okada M., Tsujikawa M., Shimomura Y., Nishida K., Inoue Y., Watanabe H., Maeda N., Kurahashi H., Kinoshita S. A kerato-epithelin (betaig-h3) mutation in lattice corneal dystrophy type IIIA. Am J Hum Genet. 1998 Mar;62(3):719–722. doi: 10.1086/301765. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The British Journal of Ophthalmology are provided here courtesy of BMJ Publishing Group

RESOURCES