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Novel FAM20A mutations in hypoplastic amelogenesis imperfecta
Author(s) -
Cho Sang Hyun,
Seymen Figen,
Lee KyungEun,
Lee SookKyung,
Kweon YoungSun,
Kim Kyung Jin,
Jung SeungEun,
Song Su Jeong,
Yildirim Mine,
Bayram Merve,
Tuna Elif Bahar,
Gencay Koray,
Kim JungWook
Publication year - 2012
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21621
Subject(s) - amelogenesis imperfecta , frameshift mutation , biology , nonsense mutation , genetics , minigene , exon , mutation , nonsense mediated decay , nonsense , mutant , phenotype , rna splicing , microbiology and biotechnology , gene , missense mutation , alternative splicing , enamel paint , medicine , rna , dentistry
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. © 2011 Wiley Periodicals, Inc.