MITOCHONDRIAL DNA DEPLETION AND MULTIPLE DELETIONS
POLG1, TK2, SUCLA2 and DGUOK Sequencing
MITOCHONDRIAL DNA ANALYSIS

Description:

Mitochondrial DNA depletion is characterized by a reduction of mtDNA content, which causes a heterogeneous group of disorders. Affected patients usually present in infancy with hypotonia, lactic acidosis, and elevated serum creatine kinase. Some may have severe, often fatal hepatocerebral problems, renal involvement, and/or multisystemic disorders. This test includes direct DNA sequencing analyses of three genes: POLG1, DGUOK, SUCLA2, and TK2.

Reasons for Referral:

To confirm a clinical diagnosis of affected individuals.

Testing Methodology:

The exons and flanking intronic regions of POLG1, DGUOK, SUCLA2, and TK2 genes are PCR amplified and sequenced.

Specimen Requirements:

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

Turnaround Time:

5 weeks

CPT Codes and Prices:

83904x98, 83898x49, 83912x4, 83891, 83894x8

Shipping Information

Forms:

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

References:

1. Carrozzo R, Bornstein B, Lucioli S, Campos Y, de la Pena P, Petit N, Dionisi-Vici C, Vilarinho L, Rizza T, Bertini E, Garesse R, Santorelli FM, Arenas J. (2003) Mutation analysis in 16 patients with mtDNA depletion. Hum. Mutat. 21: 453-454
2. Spinazzola A, Zeviani M. (2005) Disorders of nuclear-mitochondrial intergenomic signaling. Gene 354: 162-168.
3. 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.
4. 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.
5. 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.
6. Naviaux RK, Nguyen KV. (2004) POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion. Ann. Neurol. 55: 706-712.
7. Van Goethem G, Luoma P, Rantamaki M, Al Memar A, Kaakkola S, Hackman P, Krahe R, Lofgren A, Martin JJ, De Jonghe P, Suomalainen A, Udd B, Van Broeckhoven C. (2004) POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement. Neurology 63: 1251-1257.
8. Ferrari G, Lamantea E, Donati A, Filosto M, Briem E, Carrara F, Parini R, Simonati A, Santer R, Zeviani M. (2005) Infantile hepatocerebral syndromes associated with mutations in the mitochondrial DNA polymerase-gammaA. Brain 128: 723-731.

Test Code:

3080