P. Dighiero et al., Histologic phenotype-genotype correlation of corneal dystrophies associated with eight distinct mutations in the TGFBI gene, OPHTHALMOL, 108(4), 2001, pp. 818-823
Purpose: To establish a phenotype-genotype correlation of various autosomal
-dominant corneal dystrophies among French subjects.
Design: Retrospective molecular genetic study and clinicopathologic correla
tion.
Participants: Forty-four subjects from 26 unrelated French families were in
cluded in this study, and 60 corneal buttons could be examined at the histo
logic and ultrastructural levels.
Methods: Light microscopy and transmission electron microscopy were perform
ed on corneal specimens obtained during keratoplasty. Blood samples were co
llected for DNA analysis.
Main Outcome Measures: After genomic DNA extraction from peripheral blood l
eukocytes of each family member, exons of the TGFBI gene were amplified by
polymerase chain reaction (PCR), and the PCR products were directly sequenc
ed on both strands.
Results: Four different mutations were found to be responsible for dystroph
y of granular type (R555W, R124L, R124H, and R124L+delT125-delE126), three
other different mutations produced a lattice type (R124C, H626R, and A546T)
, and the last mutation identified was associated with the honeycomb-shaped
dystrophy (R555Q). Each subtype of dystrophy showed, histologically and ul
trastructurally, specific characteristics that are easily recognizable. How
ever, besides these stereotyped forms, differential histologic diagnosis of
atypical forms remains difficult, and these forms could be misdiagnosed.
Conclusions: The characteristic biomicroscopic appearance and histopatholog
ic features of each "classic" dystrophy present a significant degree of spe
cificity and generally provide an accurate diagnosis. However, atypical for
ms in which clinical and histologic data alone could be misleading, are une
quivocally diagnosed after DNA analysis. (C) 2001 by the American Academy o
f Ophthalmology.