title: Mutations in the USH1C gene associated with sector retinitis pigmentosa and hearing loss.
abstract: OBJECTIVE
  To determine the molecular cause of sector retinitis pigmentosa and hearing loss in two affected siblings.
  
  
  METHODS
  Direct DNA sequencing of the USH1C gene was performed in two affected siblings. Putative pathogenic sequence changes were assayed in their parent's chromosomes and in control chromosomes. Clinical examination included visual acuity measurement, visual field measurement, electrophysiologic assessment, and fine matrix mapping. Retinal imaging with fundus photography, scanning laser ophthalmoscope (fundus autofluorescence), and optical coherence tomography was performed. Hearing and vestibular function was also assessed.
  
  
  RESULTS
  The siblings were aged 42 years and 40 years, and both were compound heterozygotes for the p.R103H missense change and the novel splice site change c.2227-1G>A in the USH1C gene. Both alleles were found to be in trans. Neither allele was identified in a panel of 866 control chromosomes, and both were considered pathogenic. Both siblings had sector retinitis pigmentosa restricted to the inferior and nasal retina. Fundus autofluorescence imaging showed a clear demarcation between normal and abnormal areas of retina, which corresponded to areas of reduced sensitivity on fine matrix mapping and loss of visual field. Both siblings had severe hearing loss but were able to develop language.
  
  
  CONCLUSIONS
  We report a novel molecular cause of sector retinitis pigmentosa associated with hearing loss representing a new phenotype associated with mutations in the USH1C gene.
authors.affiliation: Institute of Ophthalmology, UCL, London, UK. z.saihan@ucl.ac.uk
authors.forename: Zubin
authors.initials: Z
authors.lastname: Saihan
authors.forename: Polona Le Quesne
authors.initials: Ple Q
authors.lastname: Stabej
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Robson
authors.forename: Nell
authors.initials: N
authors.lastname: Rangesh
authors.forename: Graham E
authors.initials: GE
authors.lastname: Holder
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
authors.forename: Karen P
authors.initials: KP
authors.lastname: Steel
authors.forename: Linda M
authors.initials: LM
authors.lastname: Luxon
authors.forename: Maria
authors.initials: M
authors.lastname: Bitner-Glindzicz
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Webster
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D009887:Ophthalmoscopy; D010375:Pedigree; D010641:Phenotype; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*; D017422:Sequence Analysis, DNA; D035781:Siblings; D041623:Tomography, Optical Coherence; D014724:Vestibular Function Tests; D014792:Visual Acuity
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C118970:USH1C protein, human