Dihydropyrimidine Dehydrogenase Deficiency via the DPYD Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
4389 DPYD 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4389DPYD81479 81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Dihydropyrimidine dehydrogenase (DPD) deficiency (also termed hereditary thymine-uraciluria; OMIM# 274270) is an inherited error in pyrimidine metabolism with wide phenotypic variability from serious mental and physical delays in infancy to no symptoms at all (van Kuilenburg et al. Hum Genet 104(1):1-9, 1999). The neurological symptoms in severely affected patients include microcephaly, recurrent seizures, muscular hypertonia, intellectual disability, delayed development of motor skills, and autism.

Irrespective of manifestation of symptoms, DPD-deficient patients are vulnerable to a potentially life-threatening toxic reaction to the fluoropyrimidine type of anti-cancer agents such as 5-fluorouracil (5-FU) (Tuchman et al. N Engl J Med 313(4):245-249, 1985; Milano et al. Br J Cancer 79(3-4):627-630, 1999). DPD is the rate-limiting enzyme of 5-FU catabolism and as such, a partial or complete DPD deficiency results in 5-FU toxicity (OMIM# 274270). Symptoms included stomatitis, leukopenia, thrombocytopenia, hair loss, diarrhea, fever, marked weight loss, cerebellar ataxia, and neurologic symptoms, progressing to semicoma. Although DPD deficiency is inherited in an autosomal recessive manner, 5-FU toxicity has been widely found in individuals with one mutated allele of the DPYD gene. DPD deficiency accounts for 50-75% of 5-FU associated toxicities (Ciccolini et al. Clin Colorectal Cancer 9(4):224-228, 2010). Since genotype-phenotype correlations are yet unclear, routine DPD testing to anticipate 5-FU associated toxicities is still lacking in consensus (Ciccolini et al., 2010; van Kuilenburg et al. Cancer Invest 24(2):215-217, 2006; Yen et al. Eur J Cancer 43(6):1011-1016, 2007). Therefore, this testing is NOT for complete risk evaluation of DPYD-associated fluoropyrimidine toxicities.

Genetics

DPD deficiency is an autosomal recessive disorder caused by mutations in the DPYD gene, which has 23 coding exons that encode dihydropyrimidine dehydrogenase (Cremers et al. Am J Hum Genet 47(4): 622–628, 1990). Over half of all DPYD defects are missense mutations (Human Gene Mutation Database). Partial and whole gene deletions are common, accounting for approximately 20% of documented DPYD mutations. Other genetic aberrations include nonsense, splicing mutations and small deletions. DPYD mutations are spread over the whole coding region randomly and no apparent mutational hot spots have been indicated.

Testing Strategy

This test provides full coverage of all coding exons of the DPYD gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

This test also includes targeted testing of the deep intronic splicing mutation c.1129-5923C>G (van Kuilenburg et al. Hum Genet 128(5):529-538, 2010).

Clinical Sensitivity - Sequencing with CNV PG-Select

Since partial and whole gene deletions account for approximately 20% of documented DPYD mutations, the overall DPYD mutation detection rate via DNA sequencing is estimated to be about 80% (Human Gene Mutation Database).

Indications for Test

Candidates for this test are patients with dihydropyrimidine dehydrogenase deficiency. Testing is also indicated for family members of patients who have known DPYD mutations. It should be noted that this testing is NOT for complete risk evaluation of DPYD-associated fluoropyrimidine toxicities. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in DPYD.

Gene

Official Gene Symbol OMIM ID
DPYD 612779
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Dihydropyrimidine Dehydrogenase Deficiency AR 274270

Citations

  • Ciccolini J, Gross E, Dahan L, Lacarelle B, Mercier C. 2010. Routine dihydropyrimidine dehydrogenase testing for anticipating 5-fluorouracil-related severe toxicities: hype or hope? Clin Colorectal Cancer 9: 224–228. PubMed ID: 20920994
  • Cremers, F. et al. (1990). “Deletions in patients with classical choroideremia vary in size from 45 kb to several megabases.” Am J Hum Genet 47(4): 622-628. PubMed ID: 2220804
  • Human Gene Mutation Database (Bio-base).
  • Milano, G et al. (1999) “Dihydropyrimidine dehydrogenase deficiency and fluorouracil-related toxicity.” Br J Cancer. 79(3-4):627-30. PubMed ID: 10027340
  • Tuchman, M et al. (1985) "Familial pyrimidinemia and pyrimidinuria associated with severe fluorouracil toxicity." N Engl J Med. 313(4):245-9. PubMed ID: 2989687
  • van Kuilenburg ABP. 2006. Screening for dihydropyrimidine dehydrogenase deficiency: to do or not to do, that’s the question. Cancer Invest. 24: 215–217. PubMed ID: 16537192
  • van Kuilenburg, A et al. (1999) “Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency.” Hum Genet. 104(1):1-9. PubMed ID: 10071185
  • van Kuilenburg, A et al. (2010). "Intragenic deletions and a deep intronic mutation affecting pre-mRNA splicing in the dihydropyrimidine dehydrogenase gene as novel mechanisms causing 5-fluorouracil toxicity." Hum Genet 128(5):529-538. PubMed ID: 20803296
  • Yen JL, McLeod HL. 2007. Should DPD analysis be required prior to prescribing fluoropyrimidines? Eur. J. Cancer 43: 1011-1016. PubMed ID: 17350823

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

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.

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.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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