title: Detailed assessment of renal function in a proband with Harboyan syndrome caused by a novel homozygous SLC4A11 nonsense mutation.
abstract: OBJECTIVE
  To identify the underlying molecular genetic cause of disease in a patient with Harboyan syndrome and to perform a detailed assessment of her renal function. We also assessed the influence of the SLC4A11 mutation identified on the corneal endothelium in the heterozygous state.
  
  
  METHODS
  A 55-year-old female was examined ophthalmologically, audiologically and nephrologically including 24-hour urine collection. The coding region of SLC4A11 was directly sequenced. Specular microscopy was performed in the proband's 21-year-old daughter.
  
  
  RESULTS
  The proband had bilateral iridectomy at the age of 3 months because of an initial diagnosis of congenital glaucoma and since the age of 12 years she underwent several keratoplasties in each eye. Nephrological examination did not reveal any abnormalities. Moderate bilateral sensorineural hearing loss was confirmed by audiometry. A novel homozygous mutation predicted to lead to a premature stop codon at the protein level, c.2188C>T; p.(Arg730*), was identified in SLC4A11. No changes in corneal endothelial cell morphology or density were observed in the heterozygous daughter.
  
  
  CONCLUSIONS
  In contrast to the Slc4a11(-/-) mouse, no abnormalities in daily renal ion excretion or polyuria were observed in the Harboyan syndrome patient. The mutation identified does not affect corneal endothelial cell morphology or density in the heterozygous state.
authors.affiliation: Laboratory of the Biology and Pathology of the Eye, Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Liskova
authors.forename: Lubica
authors.initials: L
authors.lastname: Dudakova
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tesar
authors.forename: Vladimira
authors.initials: V
authors.lastname: Bednarova
authors.forename: Jana
authors.initials: J
authors.lastname: Kidorova
authors.forename: Katerina
authors.initials: K
authors.lastname: Jirsova
authors.forename: Alice E
authors.initials: AE
authors.lastname: Davidson
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Hardcastle
mesh_terms: D027321:Anion Transport Proteins / Q000235:genetics*; D017920:Antiporters / Q000235:genetics*; D001299:Audiometry; D018389:Codon, Nonsense; D003317:Corneal Dystrophies, Hereditary / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D063171:Corneal Pachymetry; D004252:DNA Mutational Analysis; D004728:Endothelium, Corneal / Q000473:pathology; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000502:physiology*; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D014792:Visual Acuity / Q000502:physiology; D055815:Young Adult
chemical_list: D027321:Anion Transport Proteins; D017920:Antiporters; D018389:Codon, Nonsense; C425809:SLC4A11 protein, human