title: Spectrum of Clinical Signs and Genetic Characterization of Gelatinous Drop-Like Corneal Dystrophy in a Colombian Family.
abstract: OBJECTIVE
  To describe the clinical signs of gelatinous drop-like corneal dystrophy (GDLD) in a consanguineous Colombian family and determine the underlying genetic cause.
  
  
  METHODS
  We performed ocular examination of available family members and bidirectionally Sanger sequenced the GDLD-associated gene, TACSTD2. In one individual, the presence of subepithelial amyloid was confirmed with biopsy.
  
  
  RESULTS
  The parents were consanguineous and 5 of their 10 children had GDLD. Typical mulberry subepithelial deposits with subepithelial vascularization were present in 3 individuals; 2 individuals only had mild polymorphic anterior stromal opacity. We identified a homozygous TACSTD2 missense mutation, c.551A>G, p.(Tyr184Cys), in the affected family members. Both parents were heterozygous for the mutation, and unaffected siblings were either heterozygous or homozygous wild-type for this allele. In the Colombian population, this mutation has a minor allele frequency of 0.53%.
  
  
  CONCLUSIONS
  The clinical presentation of GDLD in this family was variable and does not solely support an age-dependent progression of the phenotype, suggesting that environmental or other genetic factors can modify phenotypic expression. The relatively high prevalence of this mutation in the Colombian population suggests that other individuals may have undiagnosed subclinical disease.
authors.affiliation: *Sección de Oftalmología, Universidad de Antioquia, Medellín, Colombia; †UCL Institute of Ophthalmology, London, United Kingdom; ‡Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia; §Facultad de Medicina, Universidad Pontificia Bolivariana, Medellín, Colombia; ¶Department of Genetics, Evolution and Environment, University College London, London, United Kingdom; ‖Moorfields Eye Hospital, London, United Kingdom; and **Servicio de Córnea y Superficie Ocular, Hospital Universitario San Vicente Fundación, Medellín, Colombia.
authors.forename: Sara
authors.initials: S
authors.lastname: Morantes
authors.forename: Cerys J
authors.initials: CJ
authors.lastname: Evans
authors.forename: Ana V
authors.initials: AV
authors.lastname: Valencia
authors.forename: Alice E
authors.initials: AE
authors.lastname: Davidson
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Hardcastle
authors.forename: Andrés
authors.initials: A
authors.lastname: Ruiz Linares
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Tuft
authors.forename: Miguel
authors.initials: M
authors.lastname: Cuevas
mesh_terms: D000293:Adolescent; D000328:Adult; D028226:Amyloidosis, Familial / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003105:Colombia / Q000453:epidemiology; D003241:Consanguinity; D003317:Corneal Dystrophies, Hereditary / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499380:TACSTD2 protein, human