Neurological Sciences

, Volume 38, Issue 4, pp 563–570 | Cite as

Novel POLG mutations and variable clinical phenotypes in 13 Italian patients

  • Paola Da Pozzo
  • Elena Cardaioli
  • Anna Rubegni
  • Gian Nicola Gallus
  • Alessandro Malandrini
  • Alessandra Rufa
  • Carla Battisti
  • Maria Alessandra Carluccio
  • Raffaele Rocchi
  • Fabio Giannini
  • Amedeo Bianchi
  • Michelangelo Mancuso
  • Gabriele Siciliano
  • Maria Teresa Dotti
  • Antonio Federico
Original Article

Abstract

POLG gene encodes the catalytic subunit of DNA polymerase gamma, essential for mitochondrial DNA (mtDNA) replication and repair. Mutations in POLG have been linked to a spectrum of clinical phenotypes, resulting in autosomal recessive or dominant mitochondrial diseases. These mutations have been associated with heterogeneous phenotypes, presenting with varying severity and at different ages of onset, ranging from the neonatal period to late adult life. We screened 13 patients for POLG mutations. All patients underwent a complete neurological examination, and in most of cases, muscle biopsy was performed. We detected 15 different variations in 13 unrelated Italian patients. Two mutations were novel and mapped in the pol domain (p.Thr989dup and p.Ala847Thr) of the enzyme. We also report new cases carrying controversial variations previously described as incompletely penetrant or a variant of unknown significance. Our study increases the range of clinical presentations associated with mutations in POLG gene, underlining some peculiar clinical features, such as PEO associated with corneal edema, and epilepsy, severe neuropathy with achalasia. The addition of two new substitutions, including the second report of an in-frame duplication, to the growing list of defects increases the value of POLG genetic diagnosis in a range of neurological presentations.

Keywords

Mitochondrial diseases DNA polymerase gamma Genetics Clinical phenotypes 

Notes

Acknowledgments

Research was supported in part by a grant from Regione Toscana and Ministry of Public Health to AF (project entitled “Risk and determinants of dementia in patients with mild cognitive impairment and brain subcortical vascular changes: a study of clinical, neuro-imaging and biological markers”).

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to declare.

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Copyright information

© Springer-Verlag Italia 2017

Authors and Affiliations

  • Paola Da Pozzo
    • 1
  • Elena Cardaioli
    • 1
  • Anna Rubegni
    • 2
  • Gian Nicola Gallus
    • 1
  • Alessandro Malandrini
    • 1
  • Alessandra Rufa
    • 1
  • Carla Battisti
    • 1
  • Maria Alessandra Carluccio
    • 1
  • Raffaele Rocchi
    • 1
  • Fabio Giannini
    • 1
  • Amedeo Bianchi
    • 3
  • Michelangelo Mancuso
    • 4
  • Gabriele Siciliano
    • 4
  • Maria Teresa Dotti
    • 1
  • Antonio Federico
    • 1
  1. 1.Department of Medical, Surgical and Neurological SciencesUniversity of SienaSienaItaly
  2. 2.IRCCS Fondazione Stella MarisPisaItaly
  3. 3.Department of NeuroscienceHospitalArezzoItaly
  4. 4.Department of Neuroscience, Neurological ClinicUniversity of PisaPisaItaly

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