Novel non‐contiguous exon duplication in choroideremia

• Published in: Clinical genetics Vol. 93; no. 1; pp. 144 - 148
• Main Authors: Edwards, T.L., Williams, J., Patrício, M.I., Simunovic, M.P., Shanks, M., Clouston, P., MacLaren, R.E.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2018
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adult; choroideremia; Choroideremia - diagnosis; Choroideremia - genetics; Choroideremia - physiopathology; copy number variation; Deoxyribonucleic acid; DNA; Exons; Exons - genetics; Gene Duplication; Gene therapy; Genetic screening; genetic testing; Humans; Male; Multiplex Polymerase Chain Reaction; ophthalmology; Photoreceptors; Proteins; retinal dystrophy; structural variation; Tomography, Optical Coherence; Transcription; Visual Acuity; retinal dystrophy; structural variation; ophthalmology; copy number variation; choroideremia; genetic testing
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/cge.13021

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.