title: Identification and characterization of a novel TACSTD2 mutation in gelatinous drop-like corneal dystrophy.
abstract: OBJECTIVE
  To study the clinical, histological, in vivo confocal microscopic, and molecular profile in a family with gelatinous drop-like corneal dystrophy (GDLD) from north India.
  
  
  METHODS
  Two siblings from a consanguineous family presented with clinical features analogous to GDLD. Detailed clinical evaluations were performed for all the available affected and unaffected members of this family. In vivo confocal microscopy and histology was done wherever necessary. DNA isolated from peripheral blood samples was subjected to polymerase chain reaction (PCR) followed by direct sequencing to detect mutations in the tumor-associated calcium signal transducer 2 (TACSTD2) gene. Protein modeling studies were done to asses the effect of the mutation on the protein structure.
  
  
  RESULTS
  The diagnosis of GDLD was established in the patient and the affected sibling on slit-lamp examinations, which revealed mulberry-like opacities in the subepithelium and anterior stroma that were confirmed on histopathology. The findings of the in vivo confocal microscopy were consistent with those reported in previous reports. Sequencing TACSTD2 revealed a novel homozygous missense mutation c.356G>A, leading to amino acid substitution C119Y in the two affected siblings. The mutation was found to be pathogenic on Sorting Intolerant From Tolerant (SIFT) analysis and was not found in normal controls and unaffected individuals of the family. A synonymous, previously reported, single nucleotide polymorphism (SNP; rs13267) was also seen in all the individuals of the family. Protein modeling studies involving wild-type and mutant protein indicated an exposed cysteine residue in the mutant protein.
  
  
  CONCLUSIONS
  A novel TACSTD2 C119Y mutation leading to an amino acid substitution was identified in two affected siblings of a family. Protein modeling studies revealed an exposed cysteine residue, which might cause interchain disulfide bond formation and protein aggregation leading to disturbed cell junctions of the corneal epithelium.
authors.affiliation: Laboratory of Cyto-Molecular Genetics, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Preeti
authors.initials: P
authors.lastname: Paliwal
authors.forename: Jaya
authors.initials: J
authors.lastname: Gupta
authors.forename: Radhika
authors.initials: R
authors.lastname: Tandon
authors.forename: Namrata
authors.initials: N
authors.lastname: Sharma
authors.forename: Jeewan S
authors.initials: JS
authors.lastname: Titiyal
authors.forename: Seema
authors.initials: S
authors.lastname: Kashyap
authors.forename: Seema
authors.initials: S
authors.lastname: Sen
authors.forename: Punit
authors.initials: P
authors.lastname: Kaur
authors.forename: Divya
authors.initials: D
authors.lastname: Dube
authors.forename: Arundhati
authors.initials: A
authors.lastname: Sharma
authors.forename: Rasik B
authors.initials: RB
authors.lastname: Vajpayee
mesh_terms: D000293:Adolescent; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics*; D002648:Child; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008957:Models, Genetic; D008958:Models, Molecular; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D017385:Sequence Homology; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499380:TACSTD2 protein, human
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