title: Congenital hereditary endothelial dystrophy caused by SLC4A11 mutations progresses to Harboyan syndrome.
abstract: OBJECTIVE
  Homozygous mutations in SLC4A11 cause 2 rare recessive conditions: congenital hereditary endothelial dystrophy (CHED), affecting the cornea alone, and Harboyan syndrome consisting of corneal dystrophy and sensorineural hearing loss. In addition, adult-onset Fuchs endothelial corneal dystrophy (FECD) is associated with dominant mutations in SLC4A11. In this report, we investigate whether patients with CHED go on to develop hearing loss and whether their parents, who are carriers of an SLC4A11 mutation, show signs of having FECD.
  
  
  METHODS
  Patients with CHED were screened for mutations in the SLC4A11 gene and underwent audiometric testing. The patients and their parents underwent a clinical examination and specular microscopy.
  
  
  RESULTS
  Molecular analyses confirmed SLC4A11 mutations in 4 affected individuals from 3 families. All the patients were found to have varying degrees of sensorineural hearing loss at a higher frequency range. Guttate lesions were seen in 2 of the 4 parents who were available for examination.
  
  
  CONCLUSIONS
  Our observations suggest that CHED caused by homozygous SLC4A11 mutations progresses to Harboyan syndrome, but the severity of this may vary considerably. Patients with CHED should therefore be monitored for progressive hearing loss. We could not determine conclusively whether the parents of the patients with CHED were at increased risk of developing late-onset FECD.
authors.affiliation: *Section of Ophthalmology and Neuroscience, Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom; †Department of Ophthalmology, St James's University Hospital, Leeds, United Kingdom; ‡Department of Biochemistry, Faculty of Medicine, National Autonomous University of Mexico (UNAM), Mexico City, Mexico; §Department of Genetics, Institute of Ophthalmology "Conde de Valenciana," Mexico City, Mexico; and ¶Department of Ophthalmology, Bradford Royal Infirmary, Bradford, United Kingdom.
authors.forename: Salina
authors.initials: S
authors.lastname: Siddiqui
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Zenteno
authors.forename: Aine
authors.initials: A
authors.lastname: Rice
authors.forename: Oscar
authors.initials: O
authors.lastname: Chacón-Camacho
authors.forename: Steven G
authors.initials: SG
authors.lastname: Naylor
authors.forename: David
authors.initials: D
authors.lastname: Rivera-de la Parra
authors.forename: David M
authors.initials: DM
authors.lastname: Spokes
authors.forename: Nigel
authors.initials: N
authors.lastname: James
authors.forename: Carmel
authors.initials: C
authors.lastname: Toomes
authors.forename: Chris F
authors.initials: CF
authors.lastname: Inglehearn
authors.forename: Manir
authors.initials: M
authors.lastname: Ali
mesh_terms: D000293:Adolescent; D000328:Adult; D027321:Anion Transport Proteins / Q000235:genetics*; D017920:Antiporters / Q000235:genetics*; D001299:Audiometry; D003317:Corneal Dystrophies, Hereditary / Q000175:diagnosis* / Q000235:genetics*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D004728:Endothelium, Corneal / Q000473:pathology*; D005091:Exons / Q000235:genetics; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D027321:Anion Transport Proteins; D017920:Antiporters; C425809:SLC4A11 protein, human