Lattice corneal dystrophy associated with the Ala546Asp and Pro551Gln missense changes in the TGFBI gene.
OBJECTIVE
To report a phenotypic variant of lattice corneal dystrophy associated with two missense changes, Ala546Asp and Pro551Gln, in the transforming growth factor-beta-induced gene (TGFBI).


METHODS
Experimental study.


METHODS
Genomic DNA was obtained from the proband as well as affected and unaffected family members. Exons 4, 11, 12, and 14 of the TGFBI gene were amplified and sequenced. Additionally, a corneal button excised from the proband was examined by light and transmission electron microscopy. Haplotype analysis was performed on the proband's family and members of a previously identified pedigree with the same TGFBI gene missense changes.


RESULTS
Bilateral, symmetric, radially arranged, branching refractile lines within and surrounding an area of central anterior stromal haze were noted in the proband. Multiple polymorphic, refractile deposits were noted in the mid and posterior stroma in both the proband and her daughter. Light and electron microscopic analyses demonstrated amyloid and excluded the presence of deposits characteristic of granular corneal dystrophy. Screening of TGFBI exon 12 in the proband and her affected daughter revealed two missense changes, Ala546Asp and Pro551Gln (both absent in 250 control chromosomes). Haplotype analysis suggested that the mutations in this family and in a previously identified pedigree reflect a founder effect, rather than an independent occurrence.


CONCLUSIONS
We present a phenotypic variant of lattice corneal dystrophy associated with the Ala546Asp and Pro551Gln missense changes in exon 12 of the TGFBI gene. A common ancestor appears to account for the missense mutations observed in this pedigree and in a previously reported family.
Aldave
Anthony J
AJ
Cornea Service, The Jules Stein Eye Institute, 100 Stein Plaza, Los Angeles, CA 90095, USA. aldave@jsei.ucla.edu
Gutmark
Julie G
JG
Yellore
Vivek S
VS
Affeldt
John A
JA
Meallet
Mario A
MA
Udar
Nitin
N
Rao
Narsing A
NA
Small
Kent W
KW
Klintworth
Gordon K
GK
D000328:Adult; D000409:Alanine; D000682:Amyloid / Q000032:analysis; D000686:Amyloidosis / Q000473:pathology; D001224:Aspartic Acid; D003315:Cornea / Q000648:ultrastructure; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005973:Glutamine; D006239:Haplotypes; D006801:Humans; D020125:Mutation, Missense; D010375:Pedigree; D011392:Proline; D016212:Transforming Growth Factor beta / Q000235:genetics*; D000099222:betaIG-H3 Protein
D000409:Alanine; D000682:Amyloid; D001224:Aspartic Acid; D016326:Extracellular Matrix Proteins; D005973:Glutamine; D011392:Proline; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein