title: Novel mutation and three other sequence variants segregating with phenotype at keratoconus 13q32 susceptibility locus.
abstract: Keratoconus (KTCN), a non-inflammatory corneal disorder characterized by stromal thinning, represents a major cause of corneal transplantations. Genetic and environmental factors have a role in the etiology of this complex disease. Previously reported linkage analysis revealed that chromosomal region 13q32 is likely to contain causative gene(s) for familial KTCN. Consequently, we have chosen eight positional candidate genes in this region: MBNL1, IPO5, FARP1, RNF113B, STK24, DOCK9, ZIC5 and ZIC2, and sequenced all of them in 51 individuals from Ecuadorian KTCN families and 105 matching controls. The mutation screening identified one mutation and three sequence variants showing 100% segregation under a dominant model with KTCN phenotype in one large Ecuadorian family. These substitutions were found in three different genes: c.2262A>C (p.Gln754His) and c.720+43A>G in DOCK9; c.2377-132A>C in IPO5 and c.1053+29G>C in STK24. PolyPhen analyses predicted that c.2262A>C (Gln754His) is possibly damaging for the protein function and structure. Our results suggest that c.2262A>C (p.Gln754His) mutation in DOCK9 may contribute to the KTCN phenotype in the large KTCN-014 family.
authors: Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32,Poznan, Poland.
authors: Marta
authors: M
authors: Czugala
authors: Justyna A
authors: JA
authors: Karolak
authors: Dorota M
authors: DM
authors: Nowak
authors: Piotr
authors: P
authors: Polakowski
authors: Jose
authors: J
authors: Pitarque
authors: Andrea
authors: A
authors: Molinari
authors: Malgorzata
authors: M
authors: Rydzanicz
authors: Bassem A
authors: BA
authors: Bejjani
authors: Beatrice Y J T
authors: BY
authors: Yue
authors: Jacek P
authors: JP
authors: Szaflik
authors: Marzena
authors: M
authors: Gajecka
mesh_terms: D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007640:Keratoconus / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016415:Sequence Alignment
chemical_list: D005136:Eye Proteins