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Novel nonsense mutation in MSX 1 in familial nonsyndromic oligodontia: subcellular localization and role of homeodomain/ MH 4
Author(s) -
Kimura Masashi,
Machida Junichiro,
Yamaguchi Seishi,
Shibata Akio,
Tatematsu Tadashi,
Miyachi Hitoshi,
Jezewski Peter A.,
Nakayama Atsuo,
Higashi Yujiro,
Shimozato Kazuo,
Tokita Yoshihito
Publication year - 2014
Publication title -
european journal of oral sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.802
H-Index - 93
eISSN - 1600-0722
pISSN - 0909-8836
DOI - 10.1111/eos.12105
Subject(s) - nonsense mutation , homeobox , oligodontia , genetics , mutation , biology , exon , mutant , axin2 , gene , microbiology and biotechnology , transcription factor , missense mutation , medicine , wnt signaling pathway , dentistry
Nonsyndromic tooth agenesis is one of the most common anomalies in human development. Part of the malformation is inherited and is associated with paired box 9 ( PAX 9 ), msh homeobox 1 ( MSX 1 ), and axin 2 ( AXIN 2 ) mutations. To obtain a comprehensive understanding of the genetic and molecular mechanisms that underlie this genetic disease, we investigated six familial and seven sporadic Japanese cases of nonsyndromic tooth agenesis. Searches for mutations in these candidate genes detected a novel nonsense mutation (c.416G>A) in exon 1 of MSX 1 from a family with oligodontia. This mutation co‐segregated in the affected family members. Moreover, this mutation produced a termination codon in the first exon and therefore the gene product (W139X) was truncated at the C terminus, hence, the entire homeodomain/MH4, which has many functions, such as DNA binding, protein‐protein interaction, and nuclear localization, was absent. We characterized the properties of this truncated MSX 1 by investigating the subcellular localization of the mutant gene product in transfected cells. The wild‐type MSX 1 localized exclusively at the nuclear periphery of transfected cells, whereas the mutant MSX 1 was stable but localized diffusely throughout the whole cell. These results indicate that W139X MSX 1 is responsible for tooth agenesis.