title: Dentin phosphoprotein frameshift mutations in hereditary dentin disorders and their variation patterns in normal human population.
abstract: BACKGROUND
  Dentin phosphoprotein (DPP) is the most abundant non-collagenous protein in dentin, which is highly phosphorylated and plays key roles in dentin biomineralization. The aetiology of isolated hereditary dentin disorders in most affected families is largely unknown and the association between DPP and dentin disorders has not been well established. This study aims to determine whether there are some involvements for DPP mutations in inherited dentin disorders and to clarify the sequence variation patterns of DPP in normal population.
  
  
  METHODS
  Genomic DNA was analysed in eight families with hereditary dentin disorders and 110 individuals in the normal population. The full coding sequence of DPP was amplified by polymerase chain reaction (PCR) and screened for mutations and variations by direct sequencing and TOPO TA-cloning sequencing.
  
  
  RESULTS
  Five frameshift mutations in DPP coding region were identified in five of the eight families. The mutations co-segregated with the disease phenotypes in affected families and were not found in 220 control chromosomes. In the normal population, we revealed 14 in-frame indels (insertion/deletion), six non-synonymous single nucleotide polymorphisms (SNPs), and five synonymous SNPs in the DPP coding region. These variants display extensive linkage disequilibrium and constitute a total of 15 haplotypes with three predominant haplotypes in the investigated normal population.
  
  
  CONCLUSIONS
  Our data provide the first evidence that DPP mutations can cause hereditary dentin disorders and suggest that in-frame length variations and missense SNPs in DPP have no obvious pathogenetic effects on dentin formation.
authors.forename: Y L
authors.initials: YL
authors.lastname: Song
authors.forename: C N
authors.initials: CN
authors.lastname: Wang
authors.forename: M W
authors.initials: MW
authors.lastname: Fan
authors.forename: B
authors.initials: B
authors.lastname: Su
authors.forename: Z
authors.initials: Z
authors.lastname: Bian
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003805:Dentin Dysplasia / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D010375:Pedigree; D010750:Phosphoproteins; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein
chemical_list: D004247:DNA; D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein