Novel FAM20A Mutations in Hypoplastic Amelogenesis Imperfecta

CHO S. H., Seymen F., LEE K., LEE S., KWEON Y., KIM K. J., ...More

HUMAN MUTATION, vol.33, no.1, pp.91-94, 2012 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 33 Issue: 1
  • Publication Date: 2012
  • Doi Number: 10.1002/humu.21621
  • Journal Name: HUMAN MUTATION
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.91-94
  • Keywords: FAM20A, amelogenesis imperfecta, hypoplastic enamel, gingival hyperplasia
  • Istanbul University Affiliated: Yes


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. Hum Mutat 33:91-94, 2012. (C) 2011 Wiley Periodicals, Inc.