Hypoplastic AI with Highly Variable Expressivity Caused by ENAM Mutations

J Dent Res. 2018 Aug;97(9):1064-1069. doi: 10.1177/0022034518763152. Epub 2018 Mar 19.

Abstract

Tooth enamel, the hardest tissue in the human body, is formed after a complex series of interactions between dental epithelial tissue and the underlying ectomesenchyme. Nonsyndromic amelogenesis imperfecta (AI) is a rare genetic disorder affecting tooth enamel without other nonoral symptoms. In this study, we identified 2 novel ENAM mutations in 2 families with hypoplastic AI by whole exome sequencing. Family 1 had a heterozygous splicing donor site mutation in intron 4, NM_031889; c.123+2T>G. Affected individuals had hypoplastic enamel with or without the characteristic horizontal hypoplastic grooves in some teeth. Family 2 had a nonsense mutation in the last exon, c.1842C>G, p.(Tyr614*), that was predicted to truncate the protein by 500 amino acids. Participating individuals had at least 1 mutant allele, while the proband had a homozygous mutation. Most interestingly, the clinical phenotype of the individuals harboring the heterozygous mutation varied from a lack of penetrance to a mild hypoplastic enamel defect. We believe that these findings will broaden our understanding of the clinical phenotype of AI caused by ENAM mutations.

Keywords: amelogenesis imperfecta; enamel; enamelin; penetrance; tooth; whole exome sequencing.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amelogenesis Imperfecta / genetics*
  • Child
  • Consanguinity
  • Exome Sequencing
  • Extracellular Matrix Proteins / genetics*
  • Female
  • Humans
  • Mutation / genetics*
  • Pedigree
  • Phenotype
  • Polymerase Chain Reaction
  • Turkey
  • Young Adult

Substances

  • ENAM protein, human
  • Extracellular Matrix Proteins

Supplementary concepts

  • Amelogenesis imperfecta local hypoplastic form