A new mutation (Leu569Arg) within exon 13 of the TGFBI (BIGH3) gene causes lattice corneal dystrophy type I.
OBJECTIVE
To describe an American family with lattice corneal dystrophy type I, which associates with a novel mutation, Leu569Arg, of the TGFBI (BIGH3) gene.


METHODS
Experimental study.


METHODS
Genomic DNA was extracted from buccal epithelial cells of four affected members of an American family with lattice corneal dystrophy type I. All 17 exons of the TGFBI gene were evaluated by PCR amplification and direct sequencing. Clinical and histologic data were also collected.


RESULTS
Three generations of this family have been positively diagnosed with lattice corneal dystrophy, indicating autosomal dominant inheritance. We identified a heterozygous point mutation that associates with the disease phenotype. The single base-pair substitution (T1753G) results in an amino acid substitution (Leu569Arg) in exon 13 of the TGFBI gene.


CONCLUSIONS
Substitution of arginine for leucine at position 569 of the TGFBI gene results in a form of lattice corneal dystrophy that is phenotypically similar to other genetically distinct forms of type I disease. This is the first report of disease correlated with changes in exon 13 of the TGFBI gene.
Francis I. Proctor Foundation and the Department of Ophthalmology, University of California, San Francisco, San Francisco, California 94143, USA. jwarren@itsa.ucsf.edu
John F
JF
Warren
Richard L
RL
Abbott
Michael K
MK
Yoon
J Brooks
JB
Crawford
William H
WH
Spencer
Todd P
TP
Margolis
D000328:Adult; D019943:Amino Acid Substitution; D001120:Arginine / Q000235:genetics*; D002675:Child, Preschool; 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; D006801:Humans; D015948:Keratoplasty, Penetrating; D007930:Leucine / Q000235:genetics*; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012008:Recurrence; D012086:Reoperation; D017422:Sequence Analysis, DNA; D016212:Transforming Growth Factor beta / Q000235:genetics; D014792:Visual Acuity; D000099222:betaIG-H3 Protein
D001120:Arginine; D016326:Extracellular Matrix Proteins; D007930:Leucine; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein