title: Keratopathy in Autoimmune Polyendocrinopathy Syndrome Type 1.
abstract: OBJECTIVE
  To report the spectrum of phenotypes in patients with autoimmune polyendocrinopathy syndrome type 1 (APS1)-related keratopathy.
  
  
  METHODS
  In this retrospective observational case series, 6 patients followed for APS1 were included. Data collected included family history, age at presentation, and systemic and ophthalmic manifestations. The 14 coding exons of the autoimmune regulator (AIRE) gene were sequenced.
  
  
  RESULTS
  The age at the onset of keratopathy ranged from 4 to 20 years. The ocular symptoms varied from mild photophobia to severe pain, and visual acuity was from light perception to 20/20 Snellen equivalent. Heterogeneous corneal involvement was observed, ranging from minimal superficial punctate staining to severe stromal scarring with deep corneal neovascularization. The severity of ophthalmic findings was uncorrelated to that of systemic manifestations. The genetic analyses identified 2 novel mutations (c.173C>A in exon 2 and c.892G>T in exon 8) and 4 known mutations (c.62C>T in exon 1, c.415C>T in exon 3, c.1096-1G>A in intron 9, and c.1193delC in exon 10) in the AIRE gene. In patients with identical AIRE mutations, including within a sib-pair, heterogeneous phenotypes were observed.
  
  
  CONCLUSIONS
  Keratopathy can be an early and severe manifestation of APS1, which contributes to the global prognosis of the disease. Its mechanisms remain to be elucidated.
authors.affiliation: *APHP, Hôpital Lariboisière, Service d'Ophtalmologie, Paris, France; †Université Paris Diderot, Sorbonne Paris Cité, Paris, France; ‡APHP, Hôpital Cochin, Service d'Ophtalmologie, Paris, France; §Université Paris Descartes, Faculté de Médecine, Paris, France; ¶Institute for Biomedical Research, Faculty of Medecine, University of Rouen, France; ‖Department of Genetics, Rouen University Hospital, Rouen, France; **AP-HP, Hôpital Robert Debré, Service d'Endocrinologie Diabétologie Pédiatrique et Centre de Référence des Maladies Endocriniennes Rares de la Croissance, and Institut National de la Santé et de la Recherche Médicale, Paris, France; and ††APHP, Hôpital Cochin, Service d'Endocrinologie, Paris, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Couturier
authors.forename: Pascale
authors.initials: P
authors.lastname: Saugier-Veber
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Carel
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bertherat
authors.forename: Antoine P
authors.initials: AP
authors.lastname: Brézin
mesh_terms: D000328:Adult; D017668:Age of Onset; D002648:Child; D003316:Corneal Diseases / Q000175:diagnosis / Q000235:genetics*; D005091:Exons / Q000235:genetics; D058447:Eye Pain / Q000175:diagnosis; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D010641:Phenotype; D020795:Photophobia / Q000175:diagnosis; D016884:Polyendocrinopathies, Autoimmune / Q000175:diagnosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics*; D014786:Vision Disorders / Q000175:diagnosis; D014792:Visual Acuity / Q000502:physiology; D055815:Young Adult; D000096927:AIRE Protein
chemical_list: D014157:Transcription Factors; D000096927:AIRE Protein