The clinical implications of molecular monitoring and analyses of inherited retinal diseases

Expert Rev Mol Diagn. 2017 Nov;17(11):1009-1021. doi: 10.1080/14737159.2017.1384314. Epub 2017 Oct 5.

Abstract

Retinal dystrophies (RDs) are the most common cause of inherited blindness and one of the most genetically heterogeneous human diseases. RDs arise from mutations in genes involved in development and function of photoreceptors or other retinal cells. Identification of the genetic defect causing RD allows accurate diagnosis, prognosis, and counseling in affected patients. Molecular diagnosis is a tremendous challenge in RDs due to their locus and phenotypic heterogeneity. As conventional DNA sequencing approaches are impractical in such situation, Next Generation Sequencing (NGS)-based protocols are needed to identify RD-causing mutations. This is being accomplished by sequencing RD gene panels or by whole exome or whole genome sequencing approaches. Areas covered: This review discusses the current strategies for molecular diagnosis in RDs including their advantages and limitations, as well as their utility in diagnosis of non-syndromic versus syndromic RDs. Results of ongoing gene therapy protocols in RDs are also presented. Expert commentary: Molecular diagnosis in RD improves the medical management of patients. Importantly, demand for molecular screening for RDs is greatly expanding not only as a result of increasing development and availability of NGS technologies, but also of the growing number of gene-based clinical trials offering a potential treatment to patients.

Keywords: Retinal dystrophies; exome sequencing; molecular diagnosis; next generation sequencing; retinitis pigmentosa.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell- and Tissue-Based Therapy / methods
  • Genetic Association Studies / methods
  • Genetic Diseases, Inborn / diagnosis*
  • Genetic Diseases, Inborn / genetics*
  • Genetic Diseases, Inborn / therapy
  • Genetic Predisposition to Disease
  • Genetic Therapy / methods
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Molecular Diagnostic Techniques*
  • Reproducibility of Results
  • Retinal Diseases / diagnosis*
  • Retinal Diseases / genetics*
  • Retinal Diseases / therapy
  • Stem Cell Transplantation / methods