Figure 1.

Mutations in the 5-prime end of DSPP causing inherited dentin defects. Top: The intron/exon structure of DSPP. The five DSPP exons are indicated by numbered boxes; the four introns are the lines connecting the exons. The numbers below each intron show the number of basepairs (bp) in that intron. The numbers below each exon show the number of bp in that exon followed by the range of amino acids encoded by it. Locations of the 15 reported DSPP 5' mutations are indicated by numbered lines, starting at the 5' end of DSPP. The first five mutations are in exon 2. We hypothesize that these mutations directly interfere with signal peptide function or cleavage. The other ten mutations cluster around the splice boundaries of exon 3. Skipping of exon 3 might affect cleavage or functioning of the DSPP signal peptide of (amino acids 1 to 15). Signal peptide malfunction is presumed to interfere with protein secretion and cause cell pathology. Middle: List of the 15 reported DSPP 5' mutations and their dental phenotypes. Note that six of the fourteen DSPP 5' mutations have been reported more than once and that the diagnoses of DGI-II or DGI-III have both been used to describe the phenotype of persons with the same DSPP mutation. Bottom: Wild-type (WT) and mutant predicted amino acid DSPP sequences. Changed amino acids are in bold and underlined; the signal peptide cleavage site is indicated by and arrow.