title: Detection and characterization of point mutations in the choroideremia candidate gene by PCR-SSCP analysis and direct DNA sequencing.
abstract: By making use of positional cloning strategies we recently isolated a candidate gene for choroideremia (CHM), which is transcribed in retina, choroid, and/or retinal pigment epithelium. The gene contains an open reading frame that is structurally altered in 10 CHM patients with sizable deletions and in a female patient with a balanced translocation involving the Xq21 band. Employing PCR-SSCP analysis and direct DNA sequencing we have now detected and characterized different point mutations in five patients with CHM. Each of these mutations introduces a termination codon into the open reading frame of the CHM candidate gene, thereby predicting a distinct truncated protein product. Together these findings provide convincing evidence for the candidate gene being identical with the choroideremia gene.
authors.affiliation: Department of Human Genetics, University Hospital Nijmegen, The Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: van den Hurk
authors.forename: T J
authors.initials: TJ
authors.lastname: van de Pol
authors.forename: C M
authors.initials: CM
authors.lastname: Molloy
authors.forename: F
authors.initials: F
authors.lastname: Brunsmann
authors.forename: K
authors.initials: K
authors.lastname: Rüther
authors.forename: E
authors.initials: E
authors.lastname: Zrenner
authors.forename: A J
authors.initials: AJ
authors.lastname: Pinckers
authors.forename: I H
authors.initials: IH
authors.lastname: Pawlowitzki
authors.forename: E M
authors.initials: EM
authors.lastname: Bleeker-Wagemakers
authors.forename: B
authors.initials: B
authors.lastname: Wieringa
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002829:Choroid / Q000503:physiopathology*; D015794:Choroideremia / Q000235:genetics*; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D004247:DNA / Q000235:genetics* / Q000302:isolation & purification; D004277:DNA, Single-Stranded / Q000235:genetics; D005091:Exons; D005260:Female; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D016366:Open Reading Frames; D010857:Pigment Epithelium of Eye / Q000502:physiology; D016133:Polymerase Chain Reaction / Q000379:methods; D012160:Retina / Q000503:physiopathology*; D014178:Translocation, Genetic; D014960:X Chromosome
chemical_list: D004277:DNA, Single-Stranded; D009838:Oligodeoxyribonucleotides; D004247:DNA