A unique corneal dystrophy of Bowman's layer and stroma associated with the Gly623Asp mutation in the transforming growth factor beta-induced (TGFBI) gene.
OBJECTIVE
To report a unique corneal dystrophy characterized by deposits at Bowman's layer and stromal lattice lines associated with the Gly623Asp missense mutation in the transforming growth factor beta-induced (TGFBI) gene.


METHODS
Experimental study.


METHODS
The proband, 3 affected siblings, 4 unaffected relatives, and 100 control individuals.


METHODS
Slit-lamp examination, photographic documentation, and isolation of genomic DNA from buccal mucosal swabs obtained from each family member examined. Exons 4 and 11 to 14 of the TGFBI gene were amplified and sequenced in these family members and in control individuals.


METHODS
Clinical characteristics of corneal opacification in affected patients and presence of coding region changes in the TGFBI gene.


RESULTS
Significant phenotypic variability, including polymorphic Bowman's layer opacities and stromal lattice lines, was noted in the 4 affected siblings who were examined. Screening of TGFBI exon 14 in the proband, 3 affected siblings, and a 19-year-old unaffected relative revealed a missense change, Gly623Asp, that was absent in the other 3 unaffected relatives screened and in 200 control chromosomes.


CONCLUSIONS
We report a novel corneal dystrophy phenotype secondary to the Gly623Asp mutation in the TGFBI gene that is associated with clinical features of both lattice corneal dystrophy and a Bowman's layer dystrophy. The presence of clinical features considered atypical for a TGFBI-associated dystrophy in this pedigree, as well as the wide range of phenotypic expressions of the Gly623Asp mutation in affected members, underscore the clinical utility of molecular genetic analysis in the diagnosis of suspected corneal dystrophies.
Aldave
Anthony J
AJ
Cornea Service, Jules Stein Eye Institute, University of California, Los Angeles, California 90095, USA. aldave@jsei.ucla.edu
Rayner
Sylvia A
SA
King
Julie A
JA
Affeldt
John A
JA
Yellore
Vivek S
VS
D000328:Adult; D000368:Aged; D001485:Basement Membrane / Q000473:pathology*; D002648:Child; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology; D003319:Corneal Stroma / Q000473:pathology*; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014792:Visual Acuity; D000099222:betaIG-H3 Protein
D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein