Novel non-contiguous exon duplication in choroideremia

Clin Genet. 2018 Jan;93(1):144-148. doi: 10.1111/cge.13021. Epub 2017 Apr 19.

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.

Keywords: choroideremia; copy number variation; genetic testing; ophthalmology; retinal dystrophy; structural variation.

Publication types

  • Case Reports

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Choroideremia / diagnosis
  • Choroideremia / genetics*
  • Choroideremia / physiopathology
  • Exons / genetics*
  • Gene Duplication*
  • Humans
  • Male
  • Multiplex Polymerase Chain Reaction
  • Tomography, Optical Coherence
  • Visual Acuity

Substances

  • Adaptor Proteins, Signal Transducing
  • CHM protein, human