A novel variant of combined granular-lattice corneal dystrophy associated with the Met619Lys mutation in the TGFBI gene.
OBJECTIVE
To report a novel mutation in TGFBI (GenBank NM_000358), p.Met619Lys, associated with a variant of combined granular-lattice corneal dystrophy.


METHODS
Slitlamp examination and DNA collection from the proband and affected and unaffected relatives. All 17 exons of TGFBI were amplified and sequenced in the proband. Exon 14 was amplified and sequenced in the proband's family members and in 100 controls. Histopathologic examination of the excised corneal buttons from the proband and 3 family members was also performed.


RESULTS
Affected individuals demonstrated an age-dependent phenotype, with the progression from central subepithelial needlelike deposits in younger individuals to polymorphic anterior stromal opacities in older family members. Screening of TGFBI in the proband demonstrated a novel mutation, p.Met619Lys, which was also present in all affected family members. Histopathologic examination revealed stromal deposits that stained with the Congo red and Masson trichrome stains as well as an antibody to the protein product of TGFBI.


CONCLUSIONS
We present a unique corneal dystrophy phenotype associated with the novel p.Met619Lys mutation in TGFBI. Clinical Relevance The atypical and variable phenotype and the demonstration of both hyaline and amyloid stromal deposits indicate that neither clinical nor histopathologic features may be relied on to accurately diagnose and classify the corneal dystrophies.
Aldave
Anthony J
AJ
Jules Stein Eye Institute, University of California, Los Angeles, CA 90095, USA. aldave@jsei.ucla.edu
Yellore
Vivek S
VS
Sonmez
Baris
B
Bourla
Nirit
N
Salem
Andrew K
AK
Khan
M Ali
MA
Rayner
Sylvia A
SA
Glasgow
Ben J
BJ
D000328:Adult; D000368:Aged; D000682:Amyloid / Q000378:metabolism; D000686:Amyloidosis / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D003317:Corneal Dystrophies, Hereditary / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D003319:Corneal Stroma / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D005091:Exons; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D016212:Transforming Growth Factor beta / Q000235:genetics*; D000099222:betaIG-H3 Protein
D000682:Amyloid; D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein