Mutations in C4orf26, encoding a peptide with in vitro hydroxyapatite crystal nucleation and growth activity, cause amelogenesis imperfecta

Am J Hum Genet. 2012 Sep 7;91(3):565-71. doi: 10.1016/j.ajhg.2012.07.020. Epub 2012 Aug 16.


Autozygosity mapping and clonal sequencing of an Omani family identified mutations in the uncharacterized gene, C4orf26, as a cause of recessive hypomineralized amelogenesis imperfecta (AI), a disease in which the formation of tooth enamel fails. Screening of a panel of 57 autosomal-recessive AI-affected families identified eight further families with loss-of-function mutations in C4orf26. C4orf26 encodes a putative extracellular matrix acidic phosphoprotein expressed in the enamel organ. A mineral nucleation assay showed that the protein's phosphorylated C terminus has the capacity to promote nucleation of hydroxyapatite, suggesting a possible function in enamel mineralization during amelogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amelogenesis / genetics
  • Amelogenesis Imperfecta / genetics*
  • Dental Enamel / metabolism
  • Durapatite / metabolism
  • Female
  • Humans
  • Male
  • Mutation
  • Nerve Tissue Proteins / genetics*
  • Pedigree


  • C4ORF48 protein, human
  • Nerve Tissue Proteins
  • Durapatite