Description:

DNA polymerase gamma is the only DNA polymerase found in mitochondria. It bears sole responsibility for mitochondrial DNA biosynthesis. Mutations in POLG1, the catalytic subunit of polymerase gamma, cause a variety of mitochondrial diseases, including dominant and recessive forms of progressive external ophthalmoplegia (PEO), Alpers syndrome, Parkinsonism, juvenile spinocerebellar ataxia-epilepsy syndrome (SCAE), as well as sensory ataxia, neuropathy, dysarthria and ophthalmoparesis (SANDO). Alpers syndrome is an early-onset fatal disease characterized by hepatic failure, intractable seizures and global neurological deterioration (OMIM#203700). SANDO is a juvenile-onset mixed sensory and cerebellar ataxia syndrome complicated by epileptic seizures and myoclonus. Accumulation of multiple mtDNA deletions in post-mitotic tissues such as muscle and brain is noted in adPEO and arPEO. Much lesser amounts of mtDNA deletion molecules are detected in the muscle tissue of patients affected with SANDO or SCAE. In contrast, depletion of liver mtDNA rather than mtDNA deletion is associated with Alpers syndrome caused by mutations in POLG1.

Reasons for Referral:

• To confirm clinical diagnosis of the affected individuals.

Testing Methodology:

The exons and flanking intron regions of POLG1 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: 4 weeks
Known Familial Mutation: 2 weeks

CPT Codes and Prices:

Index: 83904x44, 83898x12, 83922, 83891, 83894x2
Known Familial Mutation: 83904x4, 83898x2, 83912, 83891, 83894x2

References:

1. Lamantea E, Carrara F, Mariotti C, Morandi L, Tiranti V, Zeviani M. (2002) A novel nonsense mutation (Q352X) in the mitochondrial cytochrome b gene associated with a combined deficiency of complexes I and III. Neuromuscul. Disord. 12: 49-52.
2. Lamantea E, Zeviani M. (2004) Sequence analysis of familial PEO shows additional mutations associated with the 752C-->T and 3527C-->T changes in the POLG1 gene. Ann. Neurol. 56: 454-455.
3. Naviaux RK, Nguyen KV. (2004) POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion. Ann. Neurol. 55: 706-712.
4. Naviaux RK, Nyhan WL, Barshop BA, Poulton J, Markusic D, Karpinski NC, Haas RH. (1999) Mitochondrial DNA polymerase gamma deficiency and mtDNA depletion in a child with Alpers' syndrome. Ann. Neurol. 45: 54-58.
5. 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.
6. 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-gamma A. Brain 128: 723-731.

Shipping Information

Forms:

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

Test Codes:

Index: 3065
Known Familial Mutation: 3066
Prenatal: 3067

Medical Genetics Laboratories
Baylor College of Medicine · Houston, TX 77030
Phone: 1-800-411-GENE · Fax: 713-798-6584
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