DEOXYGUANOSINE KINASE (DGUOK) SEQUENCING
MITOCHONDRIAL DNA ANALYSIS
Also see: Mitochondrial DNA Depletion and Multiple Deletions

Description:

The major supply of deoxynucleotides (dNTPs) for mitochondrial DNA (mtDNA) biosynthesis comes from the salvage pathways for dNTP generation. Two primary enzymes: deoxyguanosine kinase (DGUOK, MIM601465) and thymidine kinase (TK2, MIM 188250), are responsible for the salvage biosynthesis of dNTPs necessary to maintain the balance of mitochondrial deoxynucleotide pools. Germline mutations in DGUOK and TK2 cause the hepatocerebral and myopathic forms, respectively, of mitochondrial DNA depletion syndrome (MDS). Mitochondrial DNA depletion syndrome is a heterogeneous group of disorders, which are primarily autosomal recessive and are each characterized by a reduction in copy number of mtDNA in affected tissues. The MDS can present as a hepatocerebral form, a myopathic form, a benign later-onset form, or a cardiomyopathic form. The hepatocerebral form of MDS (MIM251880) (DGUOK) is usually characterized by onset <6 months of age, early progressive liver failure, muscle hypotonia, hyperreflexia, irritability, and death by 12 months of age from liver failure.

Reasons for Referral:

To confirm a clinical diagnosis of affected individuals.

Testing Methodology:

The exons and flanking intron regions of DGUOK gene are PCR amplified and sequenced.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adult: 14 cc; Child: 6 cc; Infant: 2-3 cc

Turnaround Time:

Index: 3 weeks
Known Familial Mutation: 2 weeks

CPT Codes and Prices:

Index: 83904x10, 83898x5, 83912, 83891, 83894x2
Known Familial Mutation: 83904x4, 83898x2, 83912, 83891, 83894x2

Shipping Information

Forms:

>> Gene Sequencing Requisition or Mitochondrial Requisition - Mitochondrial Diagnostic Checklist is included
>> Prenatal Requisition

References:

1. Mandel H, Szargel R, Labay V, Elpeleg O, Saada A, Shalata A, Anbinder Y, Berkowitz D, Hartman C, Barak M, Eriksson S, Cohen N. (2001) The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA. Nat. Genet. 29: 337-341.
2. Taanman JW, Kateeb I, Muntau AC, Jaksch M, Cohen N, Mandel H. (2002) A novel mutation in the deoxyguanosine kinase gene causing depletion of mitochondrial DNA. Ann. Neurol. 52: 237-239.
3. Tadiboyina VT, Rupar A, Atkison P, Feigenbaum A, Kronick J, Wang J, Hegele RA. (2005) Novel mutation in DGUOK in hepatocerebral mitochondrial DNA depletion syndrome associated with cystathioninuria. Am. J. Med. Genet. A. 135: 289-291.

Test Codes:

Index: 3075
Known Familial Mutation: 3076
Prenatal: 3077