title: Age-severity relationships in families linked to FCD2 with retroillumination photography.
abstract: OBJECTIVE
  Fuchs corneal dystrophy (FCD) is a progressive disorder of the corneal endothelium and is pathologically defined by the presence of guttae, which are excrescences of the Descemet membrane. The present study was undertaken to investigate the age-severity relationship of the FCD2-linked disease phenotype using retroillumination photography and to compare it with the characteristics of FCD1.
  
  
  METHODS
  Two large families with multiple affected members were recruited. Exclusion analyses of the known late-onset FCD loci were completed with closely spaced STR markers, whereas genes associated with early- and late-onset FCD were investigated by bidirectional sequencing. Haplotypes were constructed, and two-point LOD scores were calculated. To document age-severity relationships, retroillumination photographs were acquired from members of both families.
  
  
  RESULTS
  Parametric linkage and haplotype analysis mapped both families to FCD2 with significant two-point LOD scores. A total of 70,249 guttae were counted in 14 persons from both families. A significant increase in guttae density in the inferotemporal region (P = 0.016) was observed, a pattern similarly observed in a family linked to FCD1. Similarly, FCD2-linked families display an exponential trend in severity with age, as was observed in a family linked to FCD1. Finally, comparison of FCD1 and FCD2 exponential models suggested that the FCD1 phenotype is significantly more severe (P = 0.01).
  
  
  CONCLUSIONS
  A combination of genetic mapping and retroillumination photography was used to quantify the severity of the disease phenotype associated with FCD2 and to compare it to the disease characteristics of FCD1. These data suggest that this approach might have sufficient resolution to discriminate between discrete genetic FCD backgrounds, which will potentially aid in patient management.
authors.affiliation: Center for Corneal Genetics, Cornea and External Disease Service, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Elyse J
authors.initials: EJ
authors.lastname: McGlumphy
authors.forename: William S
authors.initials: WS
authors.lastname: Yeo
authors.forename: S Amer
authors.initials: SA
authors.lastname: Riazuddin
authors.forename: Amr
authors.initials: A
authors.lastname: Al-Saif
authors.forename: Jiangxia
authors.initials: J
authors.lastname: Wang
authors.forename: Allen O
authors.initials: AO
authors.lastname: Eghrari
authors.forename: Danielle N
authors.initials: DN
authors.lastname: Meadows
authors.forename: David G
authors.initials: DG
authors.lastname: Emmert
authors.forename: Nicholas
authors.initials: N
authors.lastname: Katsanis
authors.forename: John D
authors.initials: JD
authors.lastname: Gottsch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D027321:Anion Transport Proteins / Q000235:genetics; D017920:Antiporters / Q000235:genetics; D005260:Female; D005642:Fuchs' Endothelial Dystrophy / Q000175:diagnosis / Q000235:genetics; D008040:Genetic Linkage; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D010781:Photography; D012720:Severity of Illness Index; D014157:Transcription Factors / Q000235:genetics; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D027321:Anion Transport Proteins; D017920:Antiporters; D018398:Homeodomain Proteins; C425809:SLC4A11 protein, human; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1
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