Targeted exome sequencing identified novel USH2A mutations in Usher syndrome families

PLoS One. 2013 May 30;8(5):e63832. doi: 10.1371/journal.pone.0063832. Print 2013.

Abstract

Usher syndrome (USH) is a leading cause of deaf-blindness in autosomal recessive trait. Phenotypic and genetic heterogeneities in USH make molecular diagnosis much difficult. This is a pilot study aiming to develop an approach based on next-generation sequencing to determine the genetic defects in patients with USH or allied diseases precisely and effectively. Eight affected patients and twelve unaffected relatives from five unrelated Chinese USH families, including 2 pseudo-dominant ones, were recruited. A total of 144 known genes of inherited retinal diseases were selected for deep exome resequencing. Through systematic data analysis using established bioinformatics pipeline and segregation analysis, a number of genetic variants were released. Eleven mutations, eight of them were novel, in the USH2A gene were identified. Biparental mutations in USH2A were revealed in 2 families with pseudo-dominant inheritance. A proband was found to have triple mutations, two of them were supposed to locate in the same chromosome. In conclusion, this study revealed the genetic defects in the USH2A gene and demonstrated the robustness of targeted exome sequencing to precisely and rapidly determine genetic defects. The methodology provides a reliable strategy for routine gene diagnosis of USH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • DNA Mutational Analysis*
  • Exome / genetics*
  • Extracellular Matrix Proteins / genetics*
  • Female
  • Humans
  • Male
  • Mutation*
  • Pedigree*
  • Phenotype
  • Reproducibility of Results
  • Usher Syndromes / diagnosis
  • Usher Syndromes / genetics*

Substances

  • Extracellular Matrix Proteins
  • USH2A protein, human

Grants and funding

This study was supported by the National Natural Science Foundation of China (H1208/81170879), the National Key Basic Research Program (2013CB967502), and the MOST Major Projects (2012YQ12008004). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.