Next generation sequencing identifies mutations in Atonal homolog 7 (ATOH7) in families with global eye developmental defects

Hum Mol Genet. 2012 Feb 15;21(4):776-83. doi: 10.1093/hmg/ddr509. Epub 2011 Nov 7.


The atonal homolog 7 (ATOH7) gene encodes a transcription factor involved in determining the fate of retinal progenitor cells and is particularly required for optic nerve and ganglion cell development. Using a combination of autozygosity mapping and next generation sequencing, we have identified homozygous mutations in this gene, p.E49V and p.P18RfsX69, in two consanguineous families diagnosed with multiple ocular developmental defects, including severe vitreoretinal dysplasia, optic nerve hypoplasia, persistent fetal vasculature, microphthalmia, congenital cataracts, microcornea, corneal opacity and nystagmus. Most of these clinical features overlap with defects in the Norrin/β-catenin signalling pathway that is characterized by dysgenesis of the retinal and hyaloid vasculature. Our findings document Mendelian mutations within ATOH7 and imply a role for this molecule in the development of structures at the front as well as the back of the eye. This work also provides further insights into the function of ATOH7, especially its importance in retinal vascular development and hyaloid regression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Consanguinity
  • DNA Mutational Analysis / methods*
  • Eye / embryology*
  • Eye / pathology
  • Eye Abnormalities / genetics
  • Eye Abnormalities / pathology
  • Eye Diseases / genetics*
  • Eye Diseases / pathology
  • Eye Proteins / metabolism
  • Humans
  • Male
  • Mutation / genetics*
  • Nerve Tissue Proteins / metabolism
  • Retina / pathology
  • beta Catenin / metabolism


  • ATOH7 protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Eye Proteins
  • NDP protein, human
  • Nerve Tissue Proteins
  • beta Catenin

Associated data

  • PDB/2QL2