Sequence variants in COL4A1 and COL4A2 genes in Ecuadorian families with keratoconus

摘要: PURPOSE: Keratoconus (KTCN) is a non-inflammatory, usually bilateral disorder of the eye which results in conical shape and progressive thinning cornea. Several studies have suggested that genetic factors play role etiology disease. loci were previously described as possible candidate regions for familial KTCN; however, no causative mutations any genes been identified these loci. The purpose this study was to evaluate collagen type IV, alpha-1 (COL4A1) alpha-2 (COL4A2) KTCN Ecuadorian families. METHODS: COL4A1 COL4A2 15 families examined with polymerase chain reaction amplification, direct sequencing all exons, promoter intron-exon junctions performed. RESULTS: Screening revealed numerous alterations coding non-coding both genes. We detected three missense substitutions COL4A1: c.19G>C (Val7Leu), c.1663A>C (Thr555Pro), c.4002A>C (Gln1334His). Five non-synonymous variants COL4A2: c.574G>T (Val192Phe), c.1550G>A (Arg517Lys), c.2048G>C (Gly683Ala), c.2102A>G (Lys701Arg), c.2152C>T (Pro718Ser). None sequence completely segregated affected phenotype. Gln1334His variant possibly damaging protein function structure. CONCLUSIONS: This first mutation screening linkage locus close Analysis indicating other are involved causation