title: Two novel mutations of TACSTD2 found in three Japanese gelatinous drop-like corneal dystrophy families with their aberrant subcellular localization.
abstract: OBJECTIVE
  To report two novel mutation of the tumor-associated calcium signal transducer 2 (TACSTD2) gene in 3 Japanese patients with gelatinous drop-like corneal dystrophy (GDLD).
  
  
  METHODS
  Genomic DNAs were extracted from the peripheral blood of 3 Japanese families. The coding region of TACSTD2 was amplified by polymerase chain reaction (PCR) and subjected to direct sequencing analysis. Plasmid vectors harboring normal and mutated TACSTD2 were transfected to the immortalized human corneal epithelial cells to identify the subcellular localization of the normal and mutated TACSTD2 gene products.
  
  
  RESULTS
  Sequencing analysis of TACSTD2 revealed two novel homozygous mutations (c.840_841insTCATCATCGCCGGCCTCATC and c.675C>A which may result in frameshift (p.Ile281SerfsX23) and nonsense (p.Tyr225X) mutations, respectively) in the 3 GDLD patients. Protein expression analysis showed that the mutated gene product was distributed diffusely in the cytoplasm, whereas the normal gene product accumulated at the cell-to-cell borders.
  
  
  CONCLUSIONS
  This study reports two novel mutations in 3 GDLD families and expands the spectrum of mutations in TACSTD2 that may cause pathological corneal amyloidosis.
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Mina
authors.initials: M
authors.lastname: Nakatsukasa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kawasaki
authors.forename: Kenta
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Hideki
authors.initials: H
authors.lastname: Fukuoka
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
authors.forename: Kohji
authors.initials: K
authors.lastname: Nishida
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kinoshita
mesh_terms: D000328:Adult; D000368:Aged; D028226:Amyloidosis, Familial / Q000235:genetics* / Q000473:pathology; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000235:genetics*; D044466:Asian People; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics*; D002461:Cell Line, Transformed; D018389:Codon, Nonsense / Q000032:analysis*; D003315:Cornea / Q000378:metabolism* / Q000473:pathology; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D016368:Frameshift Mutation; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010957:Plasmids; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014162:Transfection
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D018389:Codon, Nonsense; C499380:TACSTD2 protein, human