Faculty Collaboration Database

A novel mutation in transforming growth factor-beta induced protein (TGFβIp) reveals secondary structure perturbation in lattice corneal dystrophy. Br J Ophthalmol 2011 Oct;95(10):1457-62

Date

08/13/2011

Pubmed ID

21835759

DOI

10.1136/bjophthalmol-2011-300651

Scopus ID

2-s2.0-81155161831 (requires institutional sign-in at Scopus site)   23 Citations

Abstract

BACKGROUND: To describe mutations in the transforming growth factor-beta induced (TGFBI) gene in Asian patients with Bowman's membrane as well as stromal corneal dystrophies, and to elucidate their structural implications, using model peptides.

METHODS: Twenty-two unrelated Asian families were examined clinically including visual acuity testing and ocular examination with slit lamp biomicroscopy. Genomic DNA was extracted and the 17 exons of the TGFBI gene were amplified by PCR and sequenced bi-directionally. Biophysical techniques were used to characterise the wild type and mutant model peptides.

RESULTS: Molecular genetic analysis identified a variety of mutations in our patient series including a novel heterozygous C to A transversion mutation in exon 14 (c.1859C→A), resulting in a substitution of a highly conserved alanine residue by aspartic acid (p.A620D). Clinical presentation in the patient with the p.A620D included subepithelial scarring in addition to the linear branching opacities usually seen with lattice dystrophy. Using model peptides, we showed that A620D mutant peptide alters the secondary structure and conformational stability, and increased amyloid formation.

CONCLUSION: A novel mutation (A620D) in transforming growth factor-beta induced protein (TGFβIp) is described, expanding the repertoire of mutations in this protein. Using model peptides, we demonstrated that A→D substitution leads to perturbation of the secondary structure that may be responsible for the amyloid formation in lattice corneal dystrophy.

Author List

Lakshminarayanan R, Vithana EN, Chai SM, Chaurasia SS, Saraswathi P, Venkatraman A, Rojare C, Venkataraman D, Tan D, Aung T, Beuerman RW, Mehta JS

Author

Shyam S. Chaurasia PhD Associate Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Aged, 80 and over
Amino Acid Sequence
Amyloid
Benzothiazoles
Bowman Membrane
Child
Circular Dichroism
Contrast Sensitivity
Corneal Dystrophies, Hereditary
Corneal Stroma
Crystallography, X-Ray
Extracellular Matrix Proteins
Female
Humans
Male
Middle Aged
Molecular Sequence Data
Mutation
Polymerase Chain Reaction
Refraction, Ocular
Thiazoles
Transforming Growth Factor beta
Visual Acuity