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

Mol Vis. 2006 May 10:12:461-6.


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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

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


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