Novel FAM20A mutations in hypoplastic amelogenesis imperfecta

Hum Mutat. 2012 Jan;33(1):91-4. doi: 10.1002/humu.21621. Epub 2011 Oct 31.


Amelogenesis imperfecta (AI) is a genetically and clinically heterogeneous group of inherited dental enamel defects without any other nonoral symptoms. Recently, a disease-causing nonsense mutation (c.406C>T) in a novel gene, FAM20A, was identified in a large consanguineous family affected by AI with gingival hyperplasia. We performed mutational analyses on nine AI families with similar phenotypes and identified three homozygous mutations (c.34_35delCT, c.813-2A>G, c.1175_1179delGGCTC) in three families and a compound heterozygous mutation (c.[590-2A>G] + [c.826C>T]) in one family. An in vitro splicing assay with a minigene confirmed the mutations located in the splicing acceptor site caused the deletion of exons 3 and 6, respectively. Taking into consideration the locations of the nonsense and frameshift mutations, the mutant transcripts are most likely degraded by nonsense-mediated mRNA degradation and it results in a loss of the FAM20A protein. This study confirms the importance of the FAM20A protein in enamel biomineralization as well as tooth eruption.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amelogenesis Imperfecta / genetics*
  • Base Sequence
  • Codon, Nonsense
  • Consanguinity
  • DNA Mutational Analysis
  • Dental Enamel Proteins / genetics*
  • Exons
  • Frameshift Mutation*
  • Heterozygote
  • Homozygote
  • Humans
  • Molecular Sequence Data
  • Pedigree
  • Phenotype
  • Republic of Korea
  • Sequence Deletion*


  • Codon, Nonsense
  • Dental Enamel Proteins
  • FAM20A protein, human