title: A novel mutation in GRK1 causes Oguchi disease in a consanguineous Pakistani family.
abstract: OBJECTIVE
  The purpose of this study was to identify the underlying molecular genetic defect in a large consanguineous Pakistani family with Oguchi disease who had been given a diagnosis of autosomal recessive retinitis pigmentosa.
  
  
  METHODS
  The family was genotyped with the Affymetrix 10K single nucleotide polymorphism array. Fine-mapping of a common homozygous region on chromosome 13q was performed using fluorescent microsatellite markers. Mutation analysis was done by direct sequencing of the candidate gene GRK1 located in the region. The segregation of a novel mutation in the family and the frequency of the identified mutation in the Pakistani population were determined by StuI RFLP analysis.
  
  
  RESULTS
  Genetic mapping supported the diagnosis of typical Oguchi disease in a Pakistani family and also resulted in the identification of a novel nonsense mutation (c.614C>A; p.S205X) in exon 1 of GRK1. This mutation is predicted to result in premature termination of the protein product, thereby affecting the phototransduction cascade. A clinical reappraisal of the family revealed that all patients homozygous for this variant had Oguchi disease.
  
  
  CONCLUSIONS
  This is the first report to describe a mutation causing typical Oguchi disease in a large consanguineous Pakistani family. This mutation segregated in eight affected members.
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: Maleeha
authors.initials: M
authors.lastname: Azam
authors.forename: Rob W J
authors.initials: RW
authors.lastname: Collin
authors.forename: Muhammad Imran
authors.initials: MI
authors.lastname: Khan
authors.forename: Syed Tahir Abbas
authors.initials: ST
authors.lastname: Shah
authors.forename: Nadeem
authors.initials: N
authors.lastname: Qureshi
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ajmal
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
authors.forename: Raheel
authors.initials: R
authors.lastname: Qamar
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005128:Eye Diseases / Q000235:genetics*; D005190:Family; D005260:Female; D005654:Fundus Oculi; D051606:G-Protein-Coupled Receptor Kinase 1 / Q000737:chemistry / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010154:Pakistan; D010375:Pedigree
chemical_list: D051606:G-Protein-Coupled Receptor Kinase 1; C496764:GRK1 protein, human