A novel DSPPmutation is associated with type II dentinogenesis Imperfecta in a chinese family

Xianqin Zhang,Mugen Liu,Xiaotao Wang,Zhen Zhao,Chengqi Xu,Erjun Qu,Jingyu Liu,Lanying Chen,Qing K Wang,Wei Chang

doi:10.1186/1471-2350-8-52

Abstract

BackgroundHereditary defects of tooth dentin are classified into two main groups: dentin dysplasia (DD) (types I and II) and dentinogenesis imperfecta (DGI) (types I, II, and III). Type II DGI is one of the most common tooth defects with an autosomal dominant mode of inheritance. One disease-causing gene, the dentin sialophosphoprotein (DSPP) gene, has been reported for type II DGI.MethodsIn this study, we characterized a four-generation Chinese family with type II DGI that consists of 18 living family members, including 8 affected individuals. Linkage analysis with polymorphic markers D4S1534 and D4S414 that span the DSPP gene showed that the family is linked to DSPP. All five exons and exon-intron boundaries of DSPP were sequenced in members of type II DGI family.ResultsDirect DNA sequence analysis identified a novel mutation (c.49C→T, p.Pro17Ser) in exon 1 of the DSPP gene. The mutation spot, the Pro17 residue, is the second amino acid of the mature DSP protein, and highly conserved during evolution. The mutation was identified in all affected individuals, but not in normal family members and 100 controls.ConclusionThese results suggest that mutation p.Pro17Ser causes type II DGI in the Chinese family. This study identifies a novel mutation in the DSPP gene, and expands the spectrum of mutations that cause DGI.

Highlights

Hereditary defects of tooth dentin are classified into two main groups: dentin dysplasia (DD) and dentinogenesis imperfecta (DGI)
Our finding suggests that Pro17 is a mutational hotspot and it may be critical for the function of dentin sialophosphoprotein (DSPP) gene
Allele 1 of D4S414 and allele 4 of D4S1534 co-segregate with the disease in the family. These results suggest that the disease gene in the family is the DSPP gene

Summary

Introduction

Hereditary defects of tooth dentin are classified into two main groups: dentin dysplasia (DD) (types I and II) and dentinogenesis imperfecta (DGI) (types I, II, and III). One disease-causing gene, the dentin sialophosphoprotein (DSPP) gene, has been reported for type II DGI. Hereditary defects of tooth dentin include two types of dentin dysplasia (DDI and DDII) and three types of dentinogenesis imperfecta (DGII, II and III). Only one disease-causing gene, DSPP encoding the dentin sialophosphoprotein, has been identified for DGI [4]. The precursor is cleaved to form two mature proteins, dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). Yamakoshi et al has established that DSP is a proteoglycan, and identified a third domain, the dentin glycoprotein (DGP) domain of DSPP [8,9]

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