A corneal dystrophy associated with transforming growth factor beta-induced Gly623Asp mutation an amyloidogenic phenotype.

Détails

ID Serval
serval:BIB_0ED2173ADBEA
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Etude de cas (case report): rapporte une observation et la commente brièvement.
Collection
Publications
Institution
Titre
A corneal dystrophy associated with transforming growth factor beta-induced Gly623Asp mutation an amyloidogenic phenotype.
Périodique
Ophthalmology
Auteur⸱e⸱s
Auw-Haedrich C., Agostini H., Clausen I., Reinhard T., Eberwein P., Schorderet D.F., Gruenauer-Kloevekorn C.
ISSN
1549-4713[electronic]
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
116
Numéro
1
Pages
46-51
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article - Publication Status: ppublish
Résumé
PURPOSE: To present the light and electron microscopic findings of a unique corneal dystrophy never before described in a German family carrying the Gly623Asp Mutation of the TGFBI gene with late clinical onset. DESIGN: Experimental study. PARTICIPANTS: Four affected and 6 nonaffected family members. METHODS: Slit-lamp examination, photographic documentation, and isolation of genomic DNA from peripheral blood leucocytes obtained from each family member examined. Exons 3, 4, 5, and 11 to 14 of the TGFBI gene were amplified and sequenced in these family members. Five corneal buttons of 3 affected siblings were excised at the time of penetrating keratoplasty. Light and electron microscopic examination were performed including immunohistochemistry with antibodies against keratoepithelin (KE) 2 and 15. MAIN OUTCOME MEASURES: Clinical and histologic characteristics of corneal opacification in affected patients and presence of coding region changes in the TGFBI gene. RESULTS: The specimens showed destructive changes in Bowman's layer and the adjacent stroma. Patchy Congo red-positive amyloid deposits were found within the epithelium in 1 cornea, in Bowman's layer and in the anterior stroma of all specimens also showing KE2, but not KE15, immunostaining. Electron microscopy revealed deposits mainly located in the anterior stroma and Bowman's layer and in small amounts in the basal area of some epithelial cells. The destroyed areas were strongly Alcian blue-positive, the Masson Trichrome stain proved mainly negative for the deposits. All affected but none of the unaffected family members had a heterozygous missense mutation in exon 14 of the TGFBI gene (G-->A transition at nucleotide 1915) replacing glycin by aspartic acid amino acid (Gly623Asp) at position 623 of the KE protein. CONCLUSIONS: In contrast with the patient carrying the Gly623Asp mutation of the TGFBI gene described by Afshari et al, our cases presented with Salzmann's nodular degeneration-like clinical features and their specimens contained KE2-positive amyloid. The reason for this now "meeting the expectation histologic phenotype" is unclear. The histologic findings emphasize that this is a unique corneal dystrophy, which shares no clinical characteristics with Reis-Bücklers' dystrophy and should be treated as a distinct entity. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.
Mots-clé
Adult, Aged, Amyloid/metabolism, Amyloidosis, Familial/genetics, Amyloidosis, Familial/metabolism, Asparagine/genetics, Corneal Dystrophies, Hereditary/genetics, Corneal Dystrophies, Hereditary/metabolism, DNA Mutational Analysis, Extracellular Matrix Proteins/metabolism, Female, Glycine/genetics, Humans, Male, Middle Aged, Mutation, Missense, Pedigree, Phenotype, Polymerase Chain Reaction, Transforming Growth Factor beta/metabolism, Transforming Growth Factor beta1/genetics, Visual Acuity
Pubmed
Web of science
Création de la notice
30/09/2009 16:22
Dernière modification de la notice
20/08/2019 12:35
Données d'usage