title: USH1G with unique retinal findings caused by a novel truncating mutation identified by genome-wide linkage analysis.
abstract: OBJECTIVE
  Usher syndrome (USH) is an autosomal recessive disorder divided into three distinct clinical subtypes based on the severity of the hearing loss, manifestation of vestibular dysfunction, and the age of onset of retinitis pigmentosa and visual symptoms. To date, mutations in seven different genes have been reported to cause USH type 1 (USH1), the most severe form. Patients diagnosed with USH1 are known to be ideal candidates to benefit from cochlear implantation.
  
  
  METHODS
  Genome-wide linkage analysis using Affymetrix GeneChip Human Mapping 10K arrays were performed in three cochlear implanted Saudi siblings born from a consanguineous marriage, clinically diagnosed with USH1 by comprehensive clinical, audiological, and ophthalmological examinations. From the linkage results, the USH1G gene was screened for mutations by direct sequencing of the coding exons.
  
  
  RESULTS
  We report the identification of a novel p.S243X truncating mutation in USH1G that segregated with the disease phenotype and was not present in 300 ethnically matched normal controls. We also report on the novel retinal findings and the outcome of cochlear implantation in the affected individuals.
  
  
  CONCLUSIONS
  In addition to reporting a novel truncating mutation, this report expands the retinal phenotype in USH1G and presents the first report of successful cochlear implants in this disease.
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. fahmad@kfshrc.edu.sa
authors.forename: Faiqa
authors.initials: F
authors.lastname: Imtiaz
authors.forename: Khalid
authors.initials: K
authors.lastname: Taibah
authors.forename: Ghada
authors.initials: G
authors.lastname: Bin-Khamis
authors.forename: Shelley
authors.initials: S
authors.lastname: Kennedy
authors.forename: Amal
authors.initials: A
authors.lastname: Hemidan
authors.forename: Faisal
authors.initials: F
authors.lastname: Al-Qahtani
authors.forename: Khalid
authors.initials: K
authors.lastname: Tabbara
authors.forename: Bashayer
authors.initials: B
authors.lastname: Al Mubarak
authors.forename: Khushnooda
authors.initials: K
authors.lastname: Ramzan
authors.forename: Brian F
authors.initials: BF
authors.lastname: Meyer
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al-Owain
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003054:Cochlear Implants; D003241:Consanguinity; D005091:Exons; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D012160:Retina / Q000378:metabolism / Q000473:pathology*; D012529:Saudi Arabia; D017422:Sequence Analysis, DNA; D035781:Siblings; D052245:Usher Syndromes / Q000235:genetics* / Q000473:pathology
chemical_list: D009419:Nerve Tissue Proteins; C477452:USH1G protein, human