Journal of Neurology

, Volume 253, Issue 7, pp 869–874 | Cite as

A new POLG1 mutation with peo and severe axonal and demyelinating sensory–motor neuropathy

  • L. Santoro
  • F. Manganelli
  • R. Lanzillo
  • A. Tessa
  • F. Barbieri
  • F. Pierelli
  • G. Di Giacinto
  • V. Nigro
  • F. M. Santorelli



Progressive external ophthalmoplegia (PEO) is a mitochondrial disorder associated with defective enzymatic activities of oxidative phosphorylation (OXPHOS), depletion of mitochondrial DNA (mtDNA) and/or accumulation of mtDNA mutations and deletions. Recent positional cloning studies have linked the disease to four different chromosomal loci. Mutations in POLG1 are a frequent cause of this disorder.


We describe two first–cousins: the propositus presented with PEO,mitochondrial myopathy and neuropathy, whereas his cousin showed a Charcot– Marie–Tooth phenotype. Neurophysiological studies, peroneal muscle and sural nerve biopsies, and molecular studies of mtDNA maintenance genes (ANT1, Twinkle, POLG1, TP) and non dominant CMT–related genes (GDAP1, LMNA, GJB1) were performed.


A severe axonal degeneration was found in both patients whereas hypomyelination was observed only in the patient with PEO whose muscle biopsy specimen also showed defective OXPHOS and multiple mtDNA deletions. While no pathogenetic mutations in GDAP1, LMNA, and GJB1 were found, we identified a novel homozygous POLG1 mutation (G763R) in the PEO patient. The mutation was heterozygous in his healthy relatives and in his affected cousin.


A homozygous POLG1 mutation might explain PEO with mitochondrial abnormalities in skeletal muscle in our propositus, and it might have aggravated his axonal and hypomyelinating sensory–motor neuropathy. Most likely, his cousin had an axonal polyneuropathy with CMT phenotype of still unknown etiology.

Key words

POLG1 PEO neuropathy mitochondrial disorders 


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Copyright information

© Steinkopff-Verlag 2006

Authors and Affiliations

  • L. Santoro
    • 1
    • 2
  • F. Manganelli
    • 2
  • R. Lanzillo
    • 2
  • A. Tessa
    • 3
  • F. Barbieri
    • 2
  • F. Pierelli
    • 4
    • 5
  • G. Di Giacinto
    • 3
  • V. Nigro
    • 6
  • F. M. Santorelli
    • 3
  1. 1.Dipartimento di Scienze NeurologicheUniversità degli Studi di Napoli “Federico II”NapoliItalia
  2. 2.Department of Neurological SciencesUniversity of Naples “Federico II”NapoliItaly
  3. 3.Molecular Medicine IRCCS-Children’sHospital Bambino GesùRomeItaly
  4. 4.Department of Neurology and ORLLa Sapienza UniversityRomeItaly
  5. 5.IRCCS NeuromedPozzilli (IS)Italy
  6. 6.Dipartimento di Patologia Generale e Centro di Eccellenza sulle Malattie CardiovascolariSeconda Università degli Studi di Napoli, and Telethon Institute of Genetics and Medicine (TIGEM)NapoliItaly

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