Hereditary lattice corneal dystrophy is associated with corneal amyloid deposits enclosing C-terminal fragments of keratoepithelin

Détails

ID Serval
serval:BIB_A4533DEABE1A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Hereditary lattice corneal dystrophy is associated with corneal amyloid deposits enclosing C-terminal fragments of keratoepithelin
Périodique
Investigative Ophthalmology and Visual Science
Auteur(s)
Stix  B., Leber  M., Bingemer  P., Gross  C., Ruschoff  J., Fandrich  M., Schorderet  D. F., Vorwerk  C. K., Zacharias  M., Roessner  A., Rocken  C.
ISSN
0146-0404 (Print)
Statut éditorial
Publié
Date de publication
04/2005
Volume
46
Numéro
4
Pages
1133-9
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Apr
Résumé
PURPOSE: To investigate the molecular basis of hereditary lattice corneal dystrophy (LCD) type IIIA associated with corneal amyloid deposits afflicting several members of a four-generation family. METHODS: Histologic, immunohistochemical and biochemical studies were performed on corneal tissue samples obtained after perforating keratoplasty. DNA was extracted from peripheral blood leukocytes. All exons of the keratoepithelin-encoding TGFBI gene were amplified and sequenced. The presence of a mutation was confirmed by digestion of the isolated PCR product with the restriction enzyme AlwNI. RESULTS: The cornea of the index patient (II-1) contained large patchy deposits of amyloid, which were immunoreactive for the C terminus of keratoepithelin. Western blot analysis of the polypeptide chains extracted from the amyloid deposits of paraffin-embedded tissue revealed that these represented mainly fragments of the full-length protein. The smallest fragments were 6.5 and 6.9 kDa. DNA analyses of the TGFBI gene revealed a heterozygous T-->C transition at the second position of codon 540 in exon 12, indicating that replacement of phenylalanine by serine (Phe540Ser) leads to dominant disease. The mutation creates a new restriction site for the enzyme AlwNI. Five of the examined family members carried this mutation. Three of them (aged >/=41 years) had the disease, two family members (aged <20 years) do not yet show any clinical symptoms. An additional inconsequential single-nucleotide polymorphism (T1667C) was found at the third position of the same codon (Phe540Phe) in three unaffected family members. CONCLUSIONS: This is the first report of a single-nucleotide mutation at codon 540 of TGFBI leading to LCD, and the first to demonstrate that the amyloid deposits in LCD contain proteolytic fragments of keratoepithelin.
Mots-clé
Adult Amyloid/*metabolism Amyloidosis, Familial/*genetics/metabolism/pathology Blotting, Western Codon Cornea/*metabolism/pathology Corneal Dystrophies, Hereditary/*genetics/metabolism/pathology Electrophoresis, Polyacrylamide Gel Exons Extracellular Matrix Proteins/*genetics/metabolism Female Gene Amplification Humans Keratoplasty, Penetrating Male Middle Aged Pedigree *Point Mutation Polymerase Chain Reaction Transforming Growth Factor beta/*genetics/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/01/2008 12:58
Dernière modification de la notice
20/08/2019 15:09
Données d'usage