A novel mutation in the helix termination motif of keratin K12 in a US family with Meesmann corneal dystrophy.

Abstract

PURPOSE:

Meesmann corneal dystrophy is an autosomal dominant disorder characterized by fragility of the anterior corneal epithelium. We have previously demonstrated that this disease can be caused by mutations in the genes encoding keratins K3 or K12, the major intermediate filament proteins expressed in corneal epithelial cells. Here, we have carried out mutation analysis in a United States kindred presenting with typical features of Meesmann corneal dystrophy.

METHODS:

Exons 1 and 6 of the K12 gene (KRT12) were polymerase chain reaction amplified from the proband's and control DNA and subjected to direct automated sequencing.

RESULTS:

A heterozygous missense mutation 1300A-->G was detected in exon 6 of KRT12, predicting amino acid substitution 1426V in the helix termination motif of the K12 polypeptide. The mutation was confirmed in the proband and excluded from 50 normal individuals by restriction enzyme analysis of polymerase chain reaction products.

CONCLUSION:

We report a novel mutation in a critical molecular overlap region of K12 in a United States family with Meesmann corneal dystrophy. The results confirm that mutations in the corneal keratins (K3 or K12) can underlie Meesmann corneal dystrophy.

• Authors: C M Coleman, S Hannush, S P Covello, F J Smith, J Uitto, W H McLean
• Journal: American journal of ophthalmology (Am J Ophthalmol) Vol. 128 Issue 6 Pg. 687-91 (Dec 1999) ISSN: 0002-9394 [Print] United States
• PMID: 10612503 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA Primers
• Keratins

Topics

• Adult
• Corneal Dystrophies, Hereditary (genetics, pathology)
• DNA Mutational Analysis
• DNA Primers (chemistry)
• Family
• Humans
• Keratins (genetics)
• Male
• Mutation, Missense
• Point Mutation
• Polymerase Chain Reaction
• Sequence Analysis, DNA
• Terminator Regions, Genetic
• United States