title: Autosomal dominant pericentral retinal dystrophy caused by a novel missense mutation in the TOPORS gene.
abstract: OBJECTIVE
  This study aimed to identify the genetic cause of autosomal dominant pericentral retinal dystrophy (adPRD) in a large Norwegian family with 35 affected members.
  
  
  METHODS
  The family was characterized by clinical ophthalmological examination along with fundus photography, dark adaptometry and electroretinography. We performed a genome-wide linkage analysis followed by sequencing of a candidate gene to identify the mutation causing the disease.
  
  
  RESULTS
  The ophthalmological examinations revealed an atypical form of retinitis pigmentosa (RP), which we prefer to call adPRD. Compared with classical RP, this phenotype has a favourable prognosis. Linkage analysis showed a linkage peak covering the most recently reported adRP gene TOPORS. This gene was sequenced in 19 family members and a novel missense mutation, c.1205a>c, resulting in an amino acid substitution p.Q402P, was detected in all affected members. The mutation showed complete co-segregation with the disease in this family, with a LOD score of 7.3. It is located in a highly conserved region and alignment with the appropriate DNA sequence from other species shows complete conservation of this amino acid. The mutation was not detected in 207 healthy, unrelated controls of Norwegian origin.
  
  
  CONCLUSIONS
  We present a novel mutation in the TOPORS gene co-segregating with a distinct phenotype of adPRD in a large Norwegian family.
authors.affiliation: Department of Medical Genetics, Ullevål University Hospital, Oslo, Norway. k.k.selmer@medisin.uio.no <k.k.selmer@medisin.uio.no>
authors.forename: Kaja Kristine
authors.initials: KK
authors.lastname: Selmer
authors.forename: Jan
authors.initials: J
authors.lastname: Grøndahl
authors.forename: Ruth
authors.initials: R
authors.lastname: Riise
authors.forename: Kristin
authors.initials: K
authors.lastname: Brandal
authors.forename: Oivind
authors.initials: O
authors.lastname: Braaten
authors.forename: Ragnheidur
authors.initials: R
authors.lastname: Bragadottir
authors.forename: Dag Erik
authors.initials: DE
authors.lastname: Undlien
mesh_terms: D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D004264:DNA Topoisomerases, Type I / Q000235:genetics; D003623:Dark Adaptation; D004596:Electroretinography; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D014792:Visual Acuity; D055815:Young Adult
chemical_list: D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; C120157:TOPORS protein, human; D044767:Ubiquitin-Protein Ligases; D004264:DNA Topoisomerases, Type I