Advanced molecular approaches pave the road to a clear-cut diagnosis of hereditary retinal dystrophies

Mol Vis. 2018 Oct 19:24:679-689. eCollection 2018.

Abstract

Purpose: The aim of this study was to identify the molecular genetic basis of hereditary retinal dystrophies (HRDs) in five unrelated Iranian families.

Methods: Whole exome sequencing and Sanger sequencing were performed in all families. Variants were analyzed using various bioinformatics databases and software.

Results: Based on the selected strategies, we identified potentially causative variants in five families with HRDs: the novel homozygous deletion mutation c.586_589delTTTG (p.F196Sfs*56) in the TTC8 gene of family A, the novel homozygous missense mutation c.2389T>C (p.S797P) in the CRB1 gene in family B, the novel homozygous frameshift mutation c.2707dupA (p.S903Kfs*66) in the LRP5 gene in family C, the novel homozygous splice mutation c.584-1G>T in the MERTK gene in family D, and the novel homozygous missense mutation c.1819G>C (p.G607R) rs61749412 in the ABCA4 gene of family E.

Conclusions: This study highlights the presence of five novel variants associated with retinal dystrophies in selected Iranian families with hereditary blindness.

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Adult
  • Asian People / genetics
  • Child
  • Cytoskeletal Proteins
  • DNA Mutational Analysis
  • Exome Sequencing*
  • Eye Diseases, Hereditary / diagnosis*
  • Eye Diseases, Hereditary / genetics
  • Eye Proteins / genetics
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Infant
  • Iran
  • Low Density Lipoprotein Receptor-Related Protein-5 / genetics
  • Male
  • Membrane Proteins / genetics
  • Molecular Biology
  • Nerve Tissue Proteins / genetics
  • Pedigree
  • Proteins / genetics
  • Retinal Dystrophies / diagnosis*
  • Retinal Dystrophies / genetics
  • c-Mer Tyrosine Kinase / genetics

Substances

  • ABCA4 protein, human
  • ATP-Binding Cassette Transporters
  • CRB1 protein, human
  • Cytoskeletal Proteins
  • Eye Proteins
  • LRP5 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-5
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Proteins
  • TTC8 protein, human
  • MERTK protein, human
  • c-Mer Tyrosine Kinase