A novel mutation of the Keratin 12 gene responsible for a severe phenotype of Meesmann's corneal dystrophy.
OBJECTIVE
To determine if a mutation within the coding region of the keratin 12 gene (KRT12) is responsible for a severe form of Meesmann's corneal dystrophy.


METHODS
A family with clinically identified Meesmann's corneal dystrophy was recruited and studied. Electron microscopy was performed on scrapings of corneal epithelial cells from the proband. Mutations in the KRT12 gene were sought using direct genomic sequencing of leukocyte DNA from two affected and two unaffected family members. Subsequently, the observed mutation was screened in all available family members using polymerase chain reaction and direct sequencing.


RESULTS
A heterozygous missense mutation (Arg430Pro) was found in exon 6 of KRT12 in all 14 affected individuals studied. Unaffected family members and 100 normal controls were negative for this mutation.


CONCLUSIONS
We have identified a novel mutation in the KRT12 gene that is associated with a symptomatic phenotype of Meesmann's corneal dystrophy. This mutation results in a substitution of proline for arginine in the helix termination motif that may disrupt the normal helix, leading to a dramatic structural change of the keratin 12 protein.
Sullivan
Lori S
LS
School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
Baylin
Eric B
EB
Font
Ramon
R
Daiger
Stephen P
SP
Pepose
Jay S
JS
Clinch
Thomas E
TE
Nakamura
Hisashi
H
Zhao
Xinping C
XC
Yee
Richard W
RW
D000328:Adult; D020816:Amino Acid Motifs / Q000235:genetics; D001120:Arginine; D053559:Corneal Dystrophy, Juvenile Epithelial of Meesmann / Q000235:genetics* / Q000473:pathology; D019573:Epithelium, Corneal / Q000473:pathology; D005091:Exons; D005799:Genes, Dominant; D006579:Heterozygote; D006801:Humans; D053551:Keratin-12 / Q000235:genetics*; D008297:Male; D008854:Microscopy, Electron; D008967:Molecular Biology; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D011392:Proline; D012720:Severity of Illness Index
D053551:Keratin-12; D001120:Arginine; D011392:Proline