title: Novel non-contiguous exon duplication in choroideremia.
abstract: The importance of establishing a genetic diagnosis in patients with a choroideremia phenotype has been underscored by the advent of gene replacement therapy for this condition. Here, we describe a complex imbalance at the CHM locus in a male patient with classical disease. At the DNA level, this imbalance consists of 2 non-contiguous duplications (exons 1-2 and 9-12). Further characterization suggests the generation of 2 independent CHM transcriptional units, one of which may produce a deleted form of the Rab escort protein 1 protein. Expression of such a type of aberrant protein in photoreceptors may have important implications when considering gene therapy for this disorder.
authors.affiliation: Department of Clinical Neurosciences, Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, UK.|Oxford Eye Hospital, Oxford University Hospital NHS Foundation Trust, Oxford, UK.
authors.forename: T L
authors.initials: TL
authors.lastname: Edwards
authors.affiliation: Oxford Medical Genetics Laboratories, Churchill Hospital, Oxford University Hospital NHS Foundation Trust, Oxford, UK.
authors.forename: J
authors.identifier: http://orcid.org/0000-0003-2672-2450
authors.initials: J
authors.lastname: Williams
authors.affiliation: Department of Clinical Neurosciences, Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, UK.
authors.forename: M I
authors.identifier: http://orcid.org/0000-0003-3875-1400
authors.initials: MI
authors.lastname: Patrício
authors.affiliation: Department of Clinical Neurosciences, Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, UK.|Oxford Eye Hospital, Oxford University Hospital NHS Foundation Trust, Oxford, UK.
authors.forename: M P
authors.initials: MP
authors.lastname: Simunovic
authors.affiliation: Oxford Medical Genetics Laboratories, Churchill Hospital, Oxford University Hospital NHS Foundation Trust, Oxford, UK.
authors.forename: M
authors.initials: M
authors.lastname: Shanks
authors.affiliation: Oxford Medical Genetics Laboratories, Churchill Hospital, Oxford University Hospital NHS Foundation Trust, Oxford, UK.
authors.forename: P
authors.initials: P
authors.lastname: Clouston
authors.affiliation: Department of Clinical Neurosciences, Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, UK.|Oxford Eye Hospital, Oxford University Hospital NHS Foundation Trust, Oxford, UK.|Moorfields Eye Hospital, UCL Institute of Ophthalmology NIHR Biomedical Research Centre, London, UK.
authors.forename: R E
authors.initials: RE
authors.lastname: MacLaren
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D015794:Choroideremia / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005091:Exons / Q000235:genetics*; D020440:Gene Duplication; D006801:Humans; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D041623:Tomography, Optical Coherence; D014792:Visual Acuity
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C081787:CHM protein, human
keywords: choroideremia; copy number variation; genetic testing; ophthalmology; retinal dystrophy; structural variation