- Human pathology

Home > A. Molecular pathology > POLG


MIM.174763 15q25

Sunday 19 June 2005

Defects of mitochondrial polymerase gamma (POLG) have been found to underlie neurological diseases ranging from myopathies to parkinsonism and infantile Alpers syndrome.


Mutations in the POLG gene have emerged as one of the most common causes of inherited mitochondrial disease in children and adults.

They are responsible for a heterogeneous group of at least 7 major phenotypes of neurodegenerative disease that include:

- 1) childhood Myocerebrohepatopathy Spectrum disorders (MCHS)
- 2) Alpers syndrome (MIM.203700)
- 3) Ataxia Neuropathy Spectrum (ANS) disorders
- 4) Myoclonus Epilepsy Myopathy Sensory Ataxia (MEMSA)
- 5) autosomal recessive Progressive External Ophthalmoplegia (arPEO)
- 6) autosomal dominant Progressive External Ophthalmoplegia (adPEO) type A1 (autosomal dominant PEOA1) (MIM.157640).
- 7) sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO) (MIM.607459)


- reversible valproate hepatotoxicity due to mutations in mitochondrial DNA polymerase gamma (POLG1) (18208989)

Due to the clinical heterogeneity, time-dependent evolution of symptoms, overlapping phenotypes, and inconsistencies in muscle pathology findings, definitive diagnosis relies on the molecular finding of deleterious mutations.

See also

- inherited mitochondrial diseases


- Wong LJ, Naviaux RK, Brunetti-Pierri N, Zhang Q, Schmitt ES, Truong C, Milone M, Cohen BH, Wical B, Ganesh J, Basinger AA, Burton BK, Swoboda K, Gilbert DL, Vanderver A, Saneto RP, Maranda B, Arnold G, Abdenur JE, Waters PJ, Copeland WC. Molecular and clinical genetics of mitochondrial diseases due to POLG mutations. Hum Mutat. 2008 Jun 10. PMID: 18546365