MYOPATHIC MITOCHONDRIAL DNA DEPLETION SYNDROME
Thymidine Kinase (TK2) Sequencing
MITOCHONDRIAL DNA ANALYSIS
Also see: SUCLA2 Sequencing; SUCLG1 Sequencing; RRM2B Sequencing

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. MDS can present as a hepatocerebral form, a myopathic form, a benign later-onset form, or a cardiomyopathic form. Patients with deficiency of TK2 manifest severe skeletal myopathy in infancy.

Reasons for Referral:

To confirm a clinical diagnosis of affected individuals.

Testing Methodology:

The exons and flanking intron regions of TK2 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: 83904x20, 83898X10, 83912, 83891, 83894x2
Known Familial Mutation: 83904x4, 83912, 83898x2, 83891, 83894x2

Shipping Information

Forms:

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

References:

1. Saada A, Shaag A, Elpeleg O. (2003) mtDNA depletion myopathy: elucidation of the tissue specificity in the mitochondrial thymidine kinase (TK2) deficiency. Mol. Genet. Metab. 79: 1-5.
2. Saada A, Shaag A, Mandel H, Nevo Y, Eriksson S, Elpeleg O. (2001) Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. Nat. Genet. 29: 342-344.
3. Tulinius M, Moslemi AR, Darin N, Holme E, Oldfors A. (2005) Novel mutations in the thymidine kinase 2 gene (TK2) associated with fatal mitochondrial myopathy and mitochondrial DNA depletion. Neuromuscul. Disord. 15: 412-415.

Test Codes:

Index: 3070
Known Familial Mutation: 3071
Prenatal: 3072