Dentinogenesis Imperfecta (DGI) and Dentin Dysplasia (DD) via the DSPP Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
771 DSPP$680.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity
No disease-causing mutations outside of the DSPP gene have been identified for nonsyndromic DGI or DD.

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Clinical Features
Inherited dentin malformations are classified into three types of dentinogenesis imperfecta (DGI) and two types of dentin dysplasia (DD) (Shields et al. Arch Oral Biol 18:543-553, 1973).  

DGI-I (OMIM 166240): Syndromic DGI. This includes individuals afflicted with osteogenesis imperfecta. Both deciduous and permanent teeth are discolored (grey-yellowish) and worn. Pulpal obliteration is apparent both prior to and upon tooth eruption.  Expressivity is variable, even within a single patient, ranging from total obliteration to normal-appearing dentin. 

DGI-II (OMIM 125490): Similar to DGI-I, but penetrance is almost complete and expressivity is consistent. 

DGI-III (OMIM 125500): Phenotypic variant of DGI-II, but with large pulp chambers resembling shell teeth in deciduous teeth.  

DD-I (OMIM 125400): Deciduous and permanent teeth appear normal, but radiologically show short roots with crescent-shaped pulpal remnant parallel to the cemento-enamel junction in the  permanent teeth and total pulpal obliteration in the deciduous teeth. Non-carious teeth usually show numerous periapical radiolucencies. 

DD-II (OMIM 125420): Deciduous teeth have features of DGI-II. The permanent teeth are normal, but pulp cavities show a thistle-tube deformity and commonly contain pulp stones.
DGI (opalescent dentin) is the most common heritable dentin disease. In the United States, the prevalence is estimated between 1:6,000 and 1:8,000; DGI-III may be even more predominant in the “Brandywine isolate” population of mixed Caucasian, Black, and Amerindian (see Acevedo et al. Cells Tissues Organs 189:230-236, 2009). Mutations in the DSPP gene are known to cause DGI-II (Xiao et al. Nat Genet 27:201-204, 2001; Malmgren et al. Hum Genet 114:491-498, 2004), DGI-III (Kim et al. Hum Genet 116:186-191, 2005), and DD-II (Rajpar et al. Hum Mol Genet 11:2559-2565, 2002). Mutations in DSPP exhibit an autosomal dominant mode of inheritance. DSPP encodes a 940 amino-acid polypeptide produced in odontoblasts that is cleaved into dentin sialoprotein (DSP) and dentin phosphoprotein (DPP) (MacDougall et al. J Biol Chem 272:835-842, 1997). DSP and DPP are noncallogenous matrix proteins that play a crucial role in dentinogenesis: most causative mutations have been reported in the DSP-coding region (mainly in exons 2-3). Causative mutations are distributed rather evenly among missense / nonsense, splicing, and small deletions. The DGI phenotype is also a variable feature in many other syndromes including Osteogenesis Imperfecta (OI) and Ehlers-Danlos syndrome (EDS), Goldblatt syndrome (OMIM 184260), and Schimke immuno-osseous dysplasia (SIOD, OMIM 242900).
Testing Strategy
This test involves complete bidirectional DNA sequencing of coding exons 2-4 of DSPP plus ~10 bp of flanking non-coding DNA on either side of each exon. Exon 5 of the gene has a large repeat element; sequencing covers the 5’ portion of the coding sequence up to the repeat and the 3’ portion after the repeat along with ~10 bp of flanking non-coding DNA on either side of this exon. We will also sequence and single exon (Test #100) in family members of patients with a known mutation or to confirm research results.
Indications for Test
Patients with symptoms of DGI / DD, and patients with a history of early tooth loss.


Official Gene Symbol OMIM ID
DSPP 125485
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Genetic Counselors
  • Acevedo, A. C., (2009). "Phenotype characterization and DSPP mutational analysis of three Brazilian dentinogenesis imperfecta type II families." Cells Tissues Organs 189(1-4): 230-6. PubMed ID: 18797159
  • Dong, J., (2005). "Dentin phosphoprotein compound mutation in dentin sialophosphoprotein causes dentinogenesis imperfecta type III." Am J Med Genet A 132A(3): 305-9. PubMed ID: 15690376
  • Kim, J. W., (2005). "Mutational hot spot in the DSPP gene causing dentinogenesis imperfecta type II." Hum Genet 116(3): 186-91. PubMed ID: 15592686
  • MacDougall, M., (1997). "Dentin phosphoprotein and dentin sialoprotein are cleavage products expressed from a single transcript coded by a gene on human chromosome 4. Dentin phosphoprotein DNA sequence determination." J Biol Chem 272(2): 835-42. PubMed ID: 8995371
  • Malmgren, B., (2004). "Clinical, histopathologic, and genetic investigation in two large families with dentinogenesis imperfecta type II." Hum Genet 114(5): 491-8. PubMed ID: 14758537
  • Rajpar, M. H., (2002). "Mutation of the signal peptide region of the bicistronic gene DSPP affects translocation to the endoplasmic reticulum and results in defective dentine biomineralization." Hum Mol Genet 11(21): 2559-65. PubMed ID: 12354781
  • Shields, E. D., (1973). "A proposed classification for heritable human dentine defects with a description of a new entity." Arch Oral Biol 18(4): 543-53. PubMed ID: 4516067
  • Xiao, S., (2001). "Dentinogenesis imperfecta 1 with or without progressive hearing loss is associated with distinct mutations in DSPP." Nat Genet 27(2): 201-4. PubMed ID: 11175790
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

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Ordering Options

myPrevent - Online Ordering
  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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