Kerato-epithelin mutations in four 5q31-linked corneal dystrophies
Details
Serval ID
serval:BIB_911F1DA2003A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Kerato-epithelin mutations in four 5q31-linked corneal dystrophies
Journal
Nature Genetics
ISSN
1061-4036 (Print)
Publication state
Published
Issued date
03/1997
Volume
15
Number
3
Pages
247-51
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Mar
Research Support, Non-U.S. Gov't --- Old month value: Mar
Abstract
Granular dystrophy Groenouw type I (CDGG1), Reis-Bucklers (CDRB), lattice type I (CDL1) and Avellino (ACD) are four 5q31-linked human autosomal dominant corneal dystrophies. Clinically, they show progressive opacification of the cornea leading to severe visual handicap. The nature of the deposits remains unknown in spite of amyloid aetiology ascribed to the last two. We generated a YAC contig of the linked region and, following cDNA selection, recovered the beta ig-h3 gene. In six affected families we identified missense mutations. All detected mutations occurred at the CpG dinucleotide of two arginine codons: R555W in one CDGG1, R555Q in one CDRB, R124C in two CDL1 and R124H in two ACD families. This suggests, as the last two diseases are characterized by amyloid deposits, that R124 mutated kerato-epithelin (the product of beta ig-h3) forms amyloidogenic intermediates that precipitate in the cornea. Our data establish a common molecular origin for the 5q31-linked corneal dystrophies.
Keywords
Alternative Splicing
Base Sequence
Cells, Cultured
Chromosome Mapping
Chromosomes, Artificial, Yeast
*Chromosomes, Human, Pair 5
Cornea/metabolism
Corneal Dystrophies, Hereditary/*genetics
DNA Primers
Dinucleoside Phosphates
Exons
*Extracellular Matrix Proteins
Genes, Dominant
Humans
Introns
Linkage (Genetics)
Molecular Sequence Data
Neoplasm Proteins/*genetics
*Point Mutation
Polymerase Chain Reaction
Skin/metabolism
*Transforming Growth Factor beta
Pubmed
Web of science
Create date
28/01/2008 13:59
Last modification date
20/08/2019 15:54