title: Allelic homogeneity in Avellino corneal dystrophy due to a founder effect.
abstract: Avellino corneal dystrophy (ACD) is a common corneal dystrophy that shows allelic homogeneity, R124H mutation in the transforming growth factor beta-induced (TGFBI) gene. There are distinct phenotypes of homozygous Avellino corneal dystrophy, termed types I and II. To investigate if the difference is caused by a modifier mutation, we sequenced the entire coding region of TGFBI of two types of ACDs. The sequences obtained from each type were identical, and we could not find any nucleotide alternations. Instead, we found seven single nucleotide polymorphisms (SNPs) compared with the normal control. Primer extension analysis revealed that all 14 homozygous patients were homozygotes in each SNP, which meant that all the patients shared the same disease haplotype. Subsequent analysis of 45 heterozygous ACD patients showed strong linkage disequilibrium between disease alleles of each SNP and ACD. These results strongly suggest that the allelic homogeneity of TGFBI associated corneal dystrophies (ACD, lattice corneal dystrophy types I and III, granular corneal dystrophy and Reis-Bucklers dystrophy) might not be caused by mutation hot spots but by the founder effects.
authors.affiliation: Department of Ophthalmology, Osaka University Medical School, 2-2 Yamadaoka Suita, Osaka, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tsujikawa
authors.affiliation: Department of Ophthalmology, Osaka University Medical School, 2-2 Yamadaoka Suita, Osaka, Japan. moto@ophthal.med.osaka-u.ac.jp.
authors.forename: Motokazu
authors.initials: M
authors.lastname: Tsujikawa
authors.affiliation: Department of Ophthalmology, Osaka University Medical School, 2-2 Yamadaoka Suita, Osaka, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Ophthalmology, Osaka University Medical School, 2-2 Yamadaoka Suita, Osaka, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Maeda
authors.affiliation: Department of Ophthalmology, Osaka University Medical School, 2-2 Yamadaoka Suita, Osaka, Japan.
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Department of Ophthalmology, Osaka University Medical School, 2-2 Yamadaoka Suita, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujikado
authors.affiliation: Department of Ophthalmology, Osaka University Medical School, 2-2 Yamadaoka Suita, Osaka, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tano
mesh_terms: D000483:Alleles; D001483:Base Sequence; D003317:Corneal Dystrophies, Hereditary / Q000175:diagnosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D018703:Founder Effect; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D053773:Transforming Growth Factor beta1 / Q000235:genetics
chemical_list: D053773:Transforming Growth Factor beta1