U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

POLG-Related Spectrum Disorders

MedGen UID:
1680556
•Concept ID:
C4763519
•
Disease or Syndrome

Definition

A group of disorders with overlapping phenotypes caused by mutation(s) of the POLG gene, encoding DNA polymerase subunit gamma-1. Phenotypic variations include Alpers-Huttenlocher syndrome (AHS), childhood myocerebrohepatopathy spectrum (MCHS), myoclonic epilepsy myopathy sensory ataxia (MEMSA), ataxia neuropathy spectrum (ANS), autosomal recessive progressive external ophthalmoplegia (arPEO), and autosomal dominant progressive external ophthalmoplegia (adPEO). [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVPOLG-Related Spectrum Disorders

Recent clinical studies

Etiology

POLG-associated ataxias can represent a substantial part of recessive and sporadic ataxias in adults.
Nuzhnyi E, Seliverstov Y, Klyushnikov S, Krylova T, Tsygankova P, Bychkov I, Zakharova E, Konovalov R, Fedin P, Abramycheva N, Illarioshkin S
Clin Neurol Neurosurg 2021 Feb;201:106462. Epub 2021 Jan 7 doi: 10.1016/j.clineuro.2020.106462. PMID: 33434755
The presence of anaemia negatively influences survival in patients with POLG disease.
Hikmat O, Tzoulis C, Klingenberg C, Rasmussen M, Tallaksen CME, Brodtkorb E, Fiskerstrand T, McFarland R, Rahman S, Bindoff LA
J Inherit Metab Dis 2017 Nov;40(6):861-866. Epub 2017 Sep 1 doi: 10.1007/s10545-017-0084-9. PMID: 28865037
The clinical spectrum and natural history of early-onset diseases due to DNA polymerase gamma mutations.
Hikmat O, Tzoulis C, Chong WK, Chentouf L, Klingenberg C, Fratter C, Carr LJ, Prabhakar P, Kumaraguru N, Gissen P, Cross JH, Jacques TS, Taanman JW, Bindoff LA, Rahman S
Genet Med 2017 Nov;19(11):1217-1225. Epub 2017 Apr 27 doi: 10.1038/gim.2017.35. PMID: 28471437
Molecular and clinical genetics of mitochondrial diseases due to POLG mutations.
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
Hum Mutat 2008 Sep;29(9):E150-72. doi: 10.1002/humu.20824. PMID: 18546365Free PMC Article

Diagnosis

Clinical and molecular spectrum associated with Polymerase-γ related disorders.
Jha R, Patel H, Dubey R, Goswami JN, Bhagwat C, Saini L, K Manokaran R, John BM, Kovilapu UB, Mohimen A, Saxena A, Sondhi V
J Child Neurol 2022 Mar;37(4):246-255. Epub 2022 Jan 5 doi: 10.1177/08830738211067065. PMID: 34986040
POLG-related disorders and their neurological manifestations.
Rahman S, Copeland WC
Nat Rev Neurol 2019 Jan;15(1):40-52. doi: 10.1038/s41582-018-0101-0. PMID: 30451971Free PMC Article
ADCK3 mutations with epilepsy, stroke-like episodes and ataxia: a POLG mimic?
Hikmat O, Tzoulis C, Knappskog PM, Johansson S, Boman H, Sztromwasser P, Lien E, Brodtkorb E, Ghezzi D, Bindoff LA
Eur J Neurol 2016 Jul;23(7):1188-94. Epub 2016 Apr 23 doi: 10.1111/ene.13003. PMID: 27106809
Novel POLG mutation in a patient with sensory ataxia, neuropathy, ophthalmoparesis and stroke.
Lam CW, Law CY, Siu WK, Fung CW, Yau MM, Huen KF, Lee HH, Mak CM
Clin Chim Acta 2015 Aug 25;448:211-4. Epub 2015 Jul 11 doi: 10.1016/j.cca.2015.06.028. PMID: 26169155
Molecular and clinical genetics of mitochondrial diseases due to POLG mutations.
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
Hum Mutat 2008 Sep;29(9):E150-72. doi: 10.1002/humu.20824. PMID: 18546365Free PMC Article

Prognosis

The presence of anaemia negatively influences survival in patients with POLG disease.
Hikmat O, Tzoulis C, Klingenberg C, Rasmussen M, Tallaksen CME, Brodtkorb E, Fiskerstrand T, McFarland R, Rahman S, Bindoff LA
J Inherit Metab Dis 2017 Nov;40(6):861-866. Epub 2017 Sep 1 doi: 10.1007/s10545-017-0084-9. PMID: 28865037
Molecular and clinical genetics of mitochondrial diseases due to POLG mutations.
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
Hum Mutat 2008 Sep;29(9):E150-72. doi: 10.1002/humu.20824. PMID: 18546365Free PMC Article

Clinical prediction guides

iPSC-Derived Neurons from Patients with POLG Mutations Exhibit Decreased Mitochondrial Content and Dendrite Simplification.
Verma M, Francis L, Lizama BN, Callio J, Fricklas G, Wang KZQ, Kaufman BA, D'Aiuto L, Stolz DB, Watkins SC, Nimgaonkar VL, Soto-Gutierrez A, Goldstein A, Chu CT
Am J Pathol 2023 Feb;193(2):201-212. Epub 2022 Nov 19 doi: 10.1016/j.ajpath.2022.11.002. PMID: 36414085Free PMC Article
Clinical and Molecular Features of POLG-Related Sensory Ataxic Neuropathy with Dysarthria and Ophthalmoparesis.
Li LX, Jiang LT, Pan YG, Zhang XL, Pan LZ, Nie ZY, Chen YH, Jin LJ
J Mol Neurosci 2021 Dec;71(12):2462-2467. Epub 2021 Apr 1 doi: 10.1007/s12031-021-01831-9. PMID: 33791913
POLG-associated ataxias can represent a substantial part of recessive and sporadic ataxias in adults.
Nuzhnyi E, Seliverstov Y, Klyushnikov S, Krylova T, Tsygankova P, Bychkov I, Zakharova E, Konovalov R, Fedin P, Abramycheva N, Illarioshkin S
Clin Neurol Neurosurg 2021 Feb;201:106462. Epub 2021 Jan 7 doi: 10.1016/j.clineuro.2020.106462. PMID: 33434755
The clinical, histochemical, and molecular spectrum of PEO1 (Twinkle)-linked adPEO.
Fratter C, Gorman GS, Stewart JD, Buddles M, Smith C, Evans J, Seller A, Poulton J, Roberts M, Hanna MG, Rahman S, Omer SE, Klopstock T, Schoser B, Kornblum C, Czermin B, Lecky B, Blakely EL, Craig K, Chinnery PF, Turnbull DM, Horvath R, Taylor RW
Neurology 2010 May 18;74(20):1619-26. doi: 10.1212/WNL.0b013e3181df099f. PMID: 20479361Free PMC Article
Molecular and clinical genetics of mitochondrial diseases due to POLG mutations.
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
Hum Mutat 2008 Sep;29(9):E150-72. doi: 10.1002/humu.20824. PMID: 18546365Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Consumer resources

    Reviews

    Related information

    • ClinVar
      Related medical variations
    • GTR
      Related information in GTR
    • GTR(Clinical)
      Clinical tests in GTR
    • PMC Articles
      Related information in PubMed Central Links
    • PubMed
      Related literature resources in PubMed

    Recent activity

    Clear Turn Off Turn On

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...