A novel missense mutation in ANO5/TMEM16E is causative for gnathodiaphyseal dyplasia in a large Italian pedigree

Eur J Hum Genet. 2013 Jun;21(6):613-9. doi: 10.1038/ejhg.2012.224. Epub 2012 Oct 10.


Gnathodiaphyseal dysplasia (GDD) is an autosomal dominant syndrome characterized by frequent bone fractures at a young age, bowing of tubular bones and cemento-osseus lesions of the jawbones. Anoctamin 5 (ANO5) belongs to the anoctamin protein family that includes calcium-activated chloride channels. However, recent data together with our own experiments reported here add weight to the hypothesis that ANO5 may not function as calcium-activated chloride channel. By sequencing the entire ANO5 gene coding region and untranslated regions in a large Italian GDD family, we found a novel missense mutation causing the p.Thr513Ile substitution. The mutation segregates with the disease in the family and has never been described in any database as a polymorphism. To date, only two mutations on the same cysteine residue at position 356 of ANO5 amino-acid sequence have been described in GDD families. As ANO5 has also been found to be mutated in two different forms of muscular dystrophy, the finding of this third mutation in GDD adds clues to the role of ANO5 in these disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amino Acid Sequence
  • Anions / metabolism
  • Anoctamins
  • Base Sequence
  • Biological Transport
  • Calcium / metabolism
  • Chloride Channels / chemistry
  • Chloride Channels / genetics*
  • Family
  • Female
  • HEK293 Cells
  • Humans
  • Italy
  • Male
  • Molecular Sequence Data
  • Mutation, Missense / genetics*
  • Osteogenesis Imperfecta / diagnostic imaging
  • Osteogenesis Imperfecta / genetics*
  • Pedigree*
  • Phenotype
  • Radiography
  • Sequence Alignment


  • ANO5 protein, human
  • Anions
  • Anoctamins
  • Chloride Channels
  • Calcium

Supplementary concepts

  • Osteogenesis imperfecta, Levin type