title: Mutation spectrum in the CHM gene of Danish and Swedish choroideremia patients.
abstract: The recent isolation of the complete open reading frame of the choroideremia (CHM) gene and the characterization of the exon-intron boundaries has paved the way to mutation detection in patients with classical choroideremia. We have performed mutation screening in patients from 15 Danish and Swedish families by using Southern blot hybridization and the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) technique. Causative mutations in the CHM gene were detected in at least 12 families, indicating that a substantial part of the mutations can be identified by this approach. In four of these families deletions of different sizes were found. Thus, in one patient, the deletion resulted in the absence of only one exon, while in another the deletion comprised the entire CHM gene. Mapping of the deletion endpoints in these four patients and in another 11 male patients with sizeable deletions enabled us to construct a very detailed map of intervals 2 and 3 of Xq21. In the remaining 11 Danish and Swedish families at least 8 causative mutations were found by PCR-SSCP analysis and direct sequencing. Interestingly, all CHM gene mutations detected thus far in choroideremia patients give rise to the introduction of a premature stop codon.
authors.affiliation: Department of Human Genetics, University Hospital Nijmegen, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: van Bokhoven
authors.forename: M
authors.initials: M
authors.lastname: Schwartz
authors.forename: S
authors.initials: S
authors.lastname: Andréasson
authors.forename: J A
authors.initials: JA
authors.lastname: van den Hurk
authors.forename: L
authors.initials: L
authors.lastname: Bogerd
authors.forename: M
authors.initials: M
authors.lastname: Jay
authors.forename: K
authors.initials: K
authors.lastname: Rüther
authors.forename: B
authors.initials: B
authors.lastname: Jay
authors.forename: I H
authors.initials: IH
authors.lastname: Pawlowitzki
authors.forename: E M
authors.initials: EM
authors.lastname: Sankila
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D019883:Alkyl and Aryl Transferases; D001483:Base Sequence; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics*; D015794:Choroideremia / Q000235:genetics*; D004252:DNA Mutational Analysis; D003718:Denmark; D005091:Exons; D005260:Female; D005796:Genes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D016324:Sequence Tagged Sites; D013548:Sweden; D014960:X Chromosome; D020691:rab GTP-Binding Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C081787:CHM protein, human; D002352:Carrier Proteins; D019883:Alkyl and Aryl Transferases; D020691:rab GTP-Binding Proteins