Two mutations in the TGFBI (BIGH3) gene associated with lattice corneal dystrophy in an extensively studied family

Invest Ophthalmol Vis Sci. 2004 May;45(5):1382-8. doi: 10.1167/iovs.03-1228.


Purpose: To determine the genetic basis for lattice corneal dystrophy (LCD) in an extensively studied family.

Methods: Ten affected family members were examined clinically, and three individuals were studied with in vivo confocal microscopy and optical coherence tomography (OCT). Corneal tissues from eight affected family members were examined histopathologically. The status of the transforming growth factor beta-induced gene (TGFBI) gene was determined in each consenting family member (six affected, seven nonaffected) by amplifying, sequencing, and analyzing exons 4 and 12 of TGFBI for mutations. All exons from the entire coding region of TGFBI of one affected person were analyzed for mutations.

Results: Slit lamp biomicroscopy disclosed the clinical features of LCD in both eyes of affected individuals. In vivo confocal microscopy confirmed the presence of deposits as bright lesions within the corneal stroma. OCT revealed increased reflectivity within the corneal stroma. The corneal stroma in persons undergoing penetrating keratoplasty contained amyloid. Affected members of the family were found to have two heterozygous single-nucleotide mutations in exon 12 of the TGFBI gene (C1637A and C1652A) leading to predicted amino acid substitutions in the encoded TGFbeta-induced protein (A546D and P551Q). Mutations were not detected in exon 4. In addition, an inconsequential single-nucleotide polymorphism T1620C (F540F) was found in some affected and nonaffected family members.

Conclusions: Two mutations in the TGFBI gene (A546D and P551Q) cosegregated with LCD in an extensively studied family that lacked the R124C mutation that frequently accompanies this form of corneal amyloidosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Amino Acid Substitution
  • Amyloid / metabolism
  • Amyloidosis / genetics
  • Amyloidosis / metabolism
  • Amyloidosis / pathology
  • Corneal Dystrophies, Hereditary / genetics*
  • Corneal Dystrophies, Hereditary / metabolism
  • Corneal Dystrophies, Hereditary / pathology
  • Corneal Stroma / metabolism
  • Corneal Stroma / pathology
  • Exons / genetics
  • Extracellular Matrix Proteins / genetics*
  • Female
  • Humans
  • Male
  • Microscopy, Confocal
  • Middle Aged
  • Pedigree
  • Point Mutation*
  • Polymorphism, Single Nucleotide
  • Tomography, Optical Coherence
  • Transforming Growth Factor beta / genetics*


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