Test ID: FDPD    
Dihydropyrimidine Dehydrogenase (DPD) Gene Mutation Analysis

Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting

enzyme in the pathway for the degradation of the pyrimidine

bases, uracil and thymine. DPD also catalyzes the

detoxification of pyrimidine-based chemotherapeutic agents

(e.g. 5-fluorouracil (5-FU) and capecitabine). Decreased

DPD activity is associated with severe myelosuppression or

even lethal toxicity, in patients treated with standard

doses of 5-FU. DPD deficiency is associated with congenital

thymine-uraciluria, an autosomal recessive condition

characterized by convulsive disorders, microcephaly, and

mental retardation. The IVS14+1G>A mutation in the

splice-donor site of intron 14 of the DPD gene (located on

chromosome 1) accounts for approximately 50% of DPD

deficiency alleles.

The IVS14+1G>A mutation is detected by polymerase chain

reaction (PCR) amplification of a portion of the DPD gene,

followed by a single nucleotide primer extension reaction

using fluorescent dideoxynucleotides, and detection of the

fluorescent reaction products using an automated, capillary

DNA sequencer. Since genetic variation and other problems

can affect the accuracy of the direct mutation testing,

these results should always be interpreted in light of

clinical and familial data.

This test is performed pursuant to a license agreement with

Orchid Biosciences Inc

Test Performed By:  Quest Diagnostics Nichols Institute

                                        36608 Ortega Highway

                                        San Juan Capistrano, CA  92690