A locus for autosomal dominant keratoconus maps to human chromosome 3p14–q13

• Published in: Journal of medical genetics 2004-03, Vol.41 (3), p.188-192
• Main Authors: Brancati, F, Valente, E M, Sarkozy, A, Fehèr, J, Castori, M, Del Duca, P, Mingarelli, R, Pizzuti, A, Dallapiccola, B
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; chromosome 3; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 3 - genetics; COL8A1; Collagen; Collagen Type VIII - genetics; Deoxyribonucleic acid; Diseases of cornea, anterior segment and sclera; DNA; Female; Genes; Genes, Dominant - genetics; Genomes; Haplotypes; Humans; Italy; keratoconus; Keratoconus - genetics; Keratoconus - pathology; Keratoconus - physiopathology; Letter to JMG; linkage; Lod Score; Male; Medical sciences; Middle Aged; Mutation; Ophthalmology; Pedigree; Polymerase chain reaction; Topography
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2003.012872

[...]although a number of putative keratoconus loci have been identified so far, 1, 4- 6 this is the first locus mapped by a genomewide search in a single informative family. A number of collagen genes (that is, collagen types I and III-VIII) have been considered excellent candidates for keratoconus on the basis of their expression pattern in different layers of the cornea. 1 In particular, studies of the Descemet's membrane have shown that type VIII collagen is a major component of the hexagonal lattice of this tissue. 13, 14 Recently, missense mutations in COL8A2, which encodes the alpha2 chain of type VIII collagen, have been identified in two forms of corneal endothelial dystrophy, underlining its role in influencing the terminal differentiation of corneal endothelial cells. 15 We could not detect any pathogenic mutations in the coding sequences and exon-intron boundaries of COL8A1.