Nasal epithelial cells are a reliable source to study splicing variants in Usher syndrome

Hum Mutat. 2010 Jun;31(6):734-41. doi: 10.1002/humu.21255.

Abstract

We have shown that nasal ciliated epithelium, which can be easily biopsied under local anesthetic, provides a good source of RNA transcripts from eight of the nine known genes that cause Usher syndrome, namely, MYO7A, USH1C, CDH23, PCDH15, USH1G for Usher type 1, and USH2A, GPR98, WHRN for Usher type 2. Furthermore, the known or predicted effect on mRNA splicing of eight variants was faithfully reproduced in the biopsied sample as measured by nested RT-PCR. These included changes at the canonical acceptor site, changes within the noncanonical acceptor site and both synonymous and nonsynonymous amino acid changes. This shows that mRNA analysis by this method will help in assessing the pathogenic effect of variants, which is a major problem in the molecular diagnosis of Usher syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Base Sequence
  • Cadherin Related Proteins
  • Cadherins / genetics
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Extracellular Matrix Proteins / genetics
  • Gene Expression
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Membrane Proteins / genetics
  • Molecular Diagnostic Techniques / methods
  • Mutation*
  • Myosin VIIa
  • Myosins / genetics
  • Nasal Cavity / pathology
  • Nerve Tissue Proteins / genetics
  • Protein Isoforms / genetics
  • RNA Splice Sites / genetics*
  • RNA Splicing
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, G-Protein-Coupled / genetics
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Usher Syndromes / diagnosis
  • Usher Syndromes / genetics*

Substances

  • ADGRV1 protein, human
  • Adaptor Proteins, Signal Transducing
  • CDH23 protein, human
  • CDHR15, human
  • Cadherin Related Proteins
  • Cadherins
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • Extracellular Matrix Proteins
  • MYO7A protein, human
  • Membrane Proteins
  • Myosin VIIa
  • Nerve Tissue Proteins
  • Protein Isoforms
  • RNA Splice Sites
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • USH1C protein, human
  • USH1G protein, human
  • USH2A protein, human
  • WHRN protein, human
  • Myosins