Atypical asymmetric lattice corneal dystrophy associated with a novel homozygous mutation (Val624Met) in the TGFBI gene.
OBJECTIVE
To evaluate the TGFBI gene and the encoded transforming growth factor beta-induced protein (TGFBIp) in a 47-year-old African-American patient with an unusual atypical asymmetric lattice corneal dystrophy (LCD).


METHODS
The eyes of the proband and his brother were examined by slit-lamp biomicroscopy and their clinical records were reviewed. All 17 exons of TGFBI were evaluated in genomic DNA extracted from blood or buccal epithelial cell samples from the proband and his family members. The corneal tissue of the proband was examined histopathologically, and TGFBIp was analyzed in half of an excised corneal button.


RESULTS
The proband (who had an unusual atypical asymmetric LCD) and his brother (who had mild bilateral deep stromal opacities) were found to have homozygous Val624Met mutations in TFGBI. The proband's daughter who was heterozygous for the Val624Met mutation had no reported ophthalmic abnormalities. The corneal tissue from the proband contained TGFBIp with the Val624Met mutation. Patients with LCD have different clinical phenotypes based on their genotype. Molecular genetic analyses are becoming increasingly important in making precise diagnoses and prognostic predictions about inherited corneal disorders.


CONCLUSIONS
A novel Val624Met homozygous mutation in TGFBI was associated with atypical LCD in two family members. Symptomatic corneal disease was absent at the age of 24 years in the offspring of the proband who was heterozygous for this mutation. This is an apparent example of a TGFBI mutation that becomes evident when it is homozygous. The finding of Val624Met mutated TGFBIp in a approximately 65 kDa protein band in a reduced sodium dodecyl sulfate (SDS) gel suggests that the accumulated protein was intact TGFBIp and not a fragment of TGFBIp.
Afshari
Natalie A
NA
Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina 27705, USA. Natalie.afshari@duke.edu
Bahadur
Rosanna P
RP
Eifrig
David E
DE
Thogersen
Ida B
IB
Enghild
Jan J
JJ
Klintworth
Gordon K
GK
D001483:Base Sequence; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008715:Methionine; D008875:Middle Aged; D009154:Mutation; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014633:Valine; D000099222:betaIG-H3 Protein
D016326:Extracellular Matrix Proteins; D008715:Methionine; D016212:Transforming Growth Factor beta; D014633:Valine; D000099222:betaIG-H3 Protein