title: Choroideremia gene testing.
abstract: Choroideremia is a chorioretinal degeneration displaying X-linked recessive inheritance. In recent years, technological advances have increased the accessibility of genetic testing for mutations in the gene that lead to this disorder. The disorder itself, approaches for its detection and the steps and the rationale behind testing are outlined in this review. All mutations in the choroideremia gene result in the truncation or absence of the normal protein product Rab escort protein-1, which is a component of Rab geranylgeranyltransferase, an enzyme complex that mediates correct intracellular vesicular transport. Sequence analysis of the 15 exons of the choroideremia gene and adjacent splice sites is a primary method of mutation detection used by the authors' laboratory, through which a variety of mutations including nonsense mutations, insertions, deletions and splice site alterations have been detected. Alternatively, if no mutations are revealed using this approach, reverse transcription PCR, northern blot analysis or a protein truncation test can be employed to detect aberrantly spliced products. Immunoblot analysis can also be performed to confirm the absence of Rab escort protein-1 in affected males. Deletions create a practical problem in assessing the carrier status of females; linkage analysis with closely linked markers is the most practical approach in these cases.
authors.affiliation: University of Alberta, Department of Ophthalmology, Edmonton T6G 2H7 Canada. macdonal@ualberta.ca
authors.forename: Ian M
authors.initials: IM
authors.lastname: MacDonald
authors.forename: Christina
authors.initials: C
authors.lastname: Sereda
authors.forename: Kerry
authors.initials: K
authors.lastname: McTaggart
authors.forename: Dean
authors.initials: D
authors.lastname: Mah
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D015794:Choroideremia / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D019937:Diagnostic Techniques and Procedures / Q000191:economics / Q000706:statistics & numerical data; D005260:Female; D020549:GTP Phosphohydrolase Activators / Q000378:metabolism*; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes; D012326:RNA Splicing
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C081787:CHM protein, human; D020549:GTP Phosphohydrolase Activators; D009097:Multienzyme Complexes; D019883:Alkyl and Aryl Transferases