title: Diagnosis of autosomal dominant retinitis pigmentosa by linkage-based exclusion screening with multiple locus-specific microsatellite markers.
abstract: OBJECTIVE
  To describe a hierarchical approach for efficient genetic diagnosis of autosomal dominant retinitis pigmentosa (adRP).
  
  
  METHODS
  Forty di-, tri-, or tetra-nucleotide repeats tightly linked to 10 genes known to be responsible for adRP were identified from the human genome sequence and used as markers in multiplex amplification and genotyping, followed by linkage analysis. Discordance of cosegregation of markers and the disease excluded the majority of the examined genes as candidates, and mutation screening for the remaining genes was performed.
  
  
  RESULTS
  With this strategy, examination of an adRP-affected family indicated that 3 of 10 candidate genes segregated concordantly with the disease. Further searches for mutations revealed a novel insertion and deletion in the last exon of a splicing factor gene, PRPF8.
  
  
  CONCLUSIONS
  This systematic approach facilitates the molecular diagnosis of adRP, which is known to have a highly heterogeneous genetic background.
authors.affiliation: Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, Japan. hkondo@fukuoka-u.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kondo
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tahira
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mizota
authors.forename: Emiko
authors.initials: E
authors.lastname: Adachi-Usami
authors.forename: Kenji
authors.initials: K
authors.lastname: Oshima
authors.forename: Kenshi
authors.initials: K
authors.lastname: Hayashi
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D002675:Child, Preschool; D004247:DNA / Q000032:analysis; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D005799:Genes, Dominant; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree; D016601:RNA-Binding Proteins; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*; D020080:Tandem Repeat Sequences
chemical_list: D002352:Carrier Proteins; C115374:PRPF8 protein, human; D016601:RNA-Binding Proteins; D004247:DNA