Systemic investigation of keratoepithelin deposits in TGFBI/BIGH3-related corneal dystrophy.

Abstract

PURPOSE:

To investigate the location and tissue-specificity of the pathologic keratoepithelin (KE) deposition in a patient with a keratoepithelinopathy (KEP), TGFBI/BIGH3-related corneal dystrophy.

METHODS:

An autopsy was performed in a patient with lattice type I corneal dystrophy (LCDI) after authorization was obtained from the family. Mutation screening in TGFBI/BIGH3 was done on the patient several years ago. Eighteen different tissues or organs, including brain, heart, lung, kidney, liver, lymph nodes, spleen, aorta, esophagus, bone marrow, urinary bladder (including a papillary urothelial carcinoma), samples of a metastatic squamous cell carcinoma, adrenal gland, parathyroid gland, muscle, prostate, and cornea were investigated, and sections from the tissues were labeled with KE2 rabbit TGFBI/BIGH3 antiserum.

RESULTS:

The patient, diagnosed with LCDI and Alzheimer's disease, died at 79 years of age from a complicated chronic obstructive lung disease. Mutation analysis showed the classical Arg124Cys mutation in exon 4 of TGFBI/BIGH3, associated with LCDI. Except for the cornea, immunostaining with KE2 antisera did not reveal any deposits in any of the 17 other organs analyzed.

CONCLUSIONS:

Pathologic deposits caused by KE accumulation were only observed in the cornea and in no other tissue or organ in this patient. These results suggest a cornea-specific mechanism in the aggregation of KE. Further studies need to be done to investigate whether the degradation of mutated KE generates cornea-specific fragments that aggregate or whether the clearing of normal fragments is different in affected corneas, which then leads to aggregation.

• Authors: Ilhem El Kochairi, Igor Letovanec, Sylvie Uffer, Francis L Munier, Pascal Chaubert, Daniel F Schorderet
• Journal: Molecular vision (Mol Vis) Vol. 12 Pg. 461-6 (May 10 2006) ISSN: 1090-0535 [Electronic] United States
• PMID: 16710170 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Extracellular Matrix Proteins
• Transforming Growth Factor beta
• betaIG-H3 protein
• Arginine
• Cysteine

Topics

• Aged
• Arginine
• Cornea (metabolism, pathology)
• Corneal Dystrophies, Hereditary (complications, genetics, metabolism, pathology)
• Cysteine
• DNA Mutational Analysis
• Exons
• Extracellular Matrix Proteins (genetics, metabolism)
• Humans
• Immunohistochemistry
• Male
• Pulmonary Disease, Chronic Obstructive (complications)
• Tissue Distribution
• Transforming Growth Factor beta (genetics, metabolism)