title: Hereditary Benign Intraepithelial Dyskeratosis: Report of a Case and Re-examination of the Evidence for Locus Heterogeneity.
abstract: BACKGROUND
  Hereditary benign intraepithelial dyskeratosis (HBID) is a rare autosomal-dominant disorder of the conjunctiva and oral mucosa first described in and predominantly affecting descendents of Haliwa-Saponi Native Americans. We report a spontaneous case of histopathologically-confirmed HBID affecting an individual not of Native American ancestry.
  
  
  METHODS
  Report of a case with histopathologic examination of an excised conjunctival specimen as well as molecular and cytogenetic analysis.
  
  
  RESULTS
  A Caucasian boy with a history of oral lesions and conjunctival injection from birth developed bilateral corneal opacities at age 5 and underwent penetrating keratoplasty, with recurrence of the corneal opacification shortly after surgery. Examination of a conjunctival biopsy specimen revealed features consistent with HBID. Copy number variant (CNV) analysis revealed a de novo 4q35 duplication that overlapped the duplication previously associated with HBID, although no genes were identified in the common interval. NLRP1 gene sequencing failed to reveal a presumed pathogenic variant.
  
  
  CONCLUSIONS
  HBID may develop de novo in individuals who are not of Native American ancestry. The absence of coding regions in a duplicated region of 4q35 common to both the individual that we report and previously associated with HBID raises questions regarding the significance of this CNV in the pathogenesis of HBID.
authors.affiliation: a The Jules Stein Eye Institute, David Geffen School of Medicine at UCLA , Los Angeles , CA , USA and.
authors.forename: Tina
authors.initials: T
authors.lastname: Bui
authors.affiliation: a The Jules Stein Eye Institute, David Geffen School of Medicine at UCLA , Los Angeles , CA , USA and.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Young
authors.affiliation: a The Jules Stein Eye Institute, David Geffen School of Medicine at UCLA , Los Angeles , CA , USA and.
authors.forename: Ricardo F
authors.initials: RF
authors.lastname: Frausto
authors.affiliation: b Undiagnosed Diseases Program, Office of Rare Diseases, NIH , Bethesda , MD , USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Markello
authors.affiliation: a The Jules Stein Eye Institute, David Geffen School of Medicine at UCLA , Los Angeles , CA , USA and.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Glasgow
authors.affiliation: a The Jules Stein Eye Institute, David Geffen School of Medicine at UCLA , Los Angeles , CA , USA and.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Aldave
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D002648:Child; D058674:Chromosome Duplication / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D003229:Conjunctival Diseases / Q000175:diagnosis* / Q000235:genetics; D003318:Corneal Opacity / Q000175:diagnosis* / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics; D004848:Epithelium / Q000002:abnormalities*; D059472:Exome / Q000235:genetics; D006801:Humans; D008297:Male; D009059:Mouth Diseases / Q000175:diagnosis* / Q000235:genetics; D000070576:NLR Proteins; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012868:Skin Abnormalities / Q000175:diagnosis* / Q000235:genetics; D044465:White People
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000070576:NLR Proteins; C427903:NLRP1 protein, human
keywords: Hereditary benign intraepithelial dyskeratosis; NLRP1; segment duplication