A Splicing Mutation in VPS4B Causes Dentin Dysplasia I

Dentin dysplasia I (DDI) is an autosomal dominant disorder characterized by rootless teeth with abnormal pulpal morphology. The etiology of DDI still remains largely unclear. Here, we identified VPS4B as a disease-causing gene for DDI by linkage analysis followed by deep sequencing of the candidate genes in a large Chinese family with DDI. A splicing mutation (IVS7+46C>G) in VPS4B gene was found, which resulted in the aberrant transcripts with a 15-amino acid insertion and loss of function. We showed that VPS4B was identified to be linked to Wnt/beta-catenin signaling and other genes involved in odontogenesis by a functional study. (By Prof. Fu Xiong, http://jmg.bmj.com/content/early/2016/05/31/jmedgenet-2015-103619 )