title: Gelatinous drop-like corneal dystrophy.
abstract: Gelatinous drop-like corneal dystrophy (GDLD) is a rare autosomal recessive disorder, clinically characterized by grayish corneal deposits of amyloid and by severely impaired visual acuity. Most patients require corneal transplantation. We identified the gene responsible for GDLD, tumor-associated calcium signal transducer 2 (TACSTD2), by positional cloning and detected 4 disease-causing mutations in Japanese patients with GDLD. During the positional cloning process, strong linkage disequilibrium was observed between GDLD and some markers in the critical region. More than 90% of GDLD patients possessed the same haplotype with a Q118X mutation in TACSTD2. This may be the result of a founder effect and reflects that most GDLD patients are Japanese. TACSTD2 deleterious mutations resulted in destabilized tight junction proteins, including claudins, ZO-1, and occludin. These findings may explain why the corneal epithelium barrier function is impaired in GDLD patients.
authors.affiliation: Department of Ophthalmology, Osaka University Medical School, Osaka, Japan. moto@ophthal.med.osaka-u.ac.jp
authors.forename: Motokazu
authors.initials: M
authors.lastname: Tsujikawa
mesh_terms: D028226:Amyloidosis, Familial / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000951:Antigens, Neoplasm / Q000235:genetics*; D015152:Blotting, Northern; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002874:Chromosome Mapping; D057167:Claudins / Q000378:metabolism; D018388:Codon, Terminator; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018703:Founder Effect; D008040:Genetic Linkage; D006801:Humans; D015810:Linkage Disequilibrium; D009154:Mutation; D062793:Occludin / Q000378:metabolism; D062725:Tight Junction Proteins / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D057167:Claudins; D018388:Codon, Terminator; C568985:OCLN protein, human; D062793:Occludin; C499380:TACSTD2 protein, human; C569042:TJP1 protein, human; D062725:Tight Junction Proteins; D062826:Zonula Occludens-1 Protein