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Journal of Neurology

, Volume 261, Issue 3, pp 504–510 | Cite as

The m.3243A>G mitochondrial DNA mutation and related phenotypes. A matter of gender?

  • Michelangelo Mancuso
  • Daniele Orsucci
  • Corrado Angelini
  • Enrico Bertini
  • Valerio Carelli
  • Giacomo Pietro Comi
  • Alice Donati
  • Carlo Minetti
  • Maurizio Moggio
  • Tiziana Mongini
  • Serenella Servidei
  • Paola Tonin
  • Antonio Toscano
  • Graziella Uziel
  • Claudio Bruno
  • Elena Caldarazzo Ienco
  • Massimiliano Filosto
  • Costanza Lamperti
  • Michela Catteruccia
  • Isabella Moroni
  • Olimpia Musumeci
  • Elena Pegoraro
  • Dario Ronchi
  • Filippo Maria Santorelli
  • Donato Sauchelli
  • Mauro Scarpelli
  • Monica Sciacco
  • Maria Lucia Valentino
  • Liliana Vercelli
  • Massimo Zeviani
  • Gabriele Siciliano
Original Communication

Abstract

The m.3243A>G “MELAS” (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) mutation is one of the most common point mutations of the mitochondrial DNA, but its phenotypic variability is incompletely understood. The aim of this study was to revise the phenotypic spectrum associated with the mitochondrial m.3243A>G mutation in 126 Italian carriers of the mutation, by a retrospective, database-based study (“Nation-wide Italian Collaborative Network of Mitochondrial Diseases”). Our results confirmed the high clinical heterogeneity of the m.3243A>G mutation. Hearing loss and diabetes were the most frequent clinical features, followed by stroke-like episodes. “MIDD” (maternally-inherited diabetes and deafness) and “PEO” (progressive external ophthalmoplegia) are nosographic terms without any real prognostic value, because these patients may be even more prone to the development of multisystem complications such as stroke-like episodes and heart involvement. The “MELAS” acronym is convincing and useful to denote patients with histological, biochemical and/or molecular evidence of mitochondrial disease who experience stroke-like episodes. Of note, we observed for the first time that male gender could represent a risk factor for the development of stroke-like episodes in Italian m.3243A>G carriers. Gender effect is not a new concept in mitochondrial medicine, but it has never been observed in MELAS. A better elucidation of the complex network linking mitochondrial dysfunction, apoptosis, estrogen effects and stroke-like episodes may hold therapeutic promises.

Keywords

A3243G MELAS MIDD Mitochondrial DNA PEO Stroke-like episodes 

Notes

Acknowledgments

This work was supported by Telethon (grant number GUP09004). The authors are grateful to the Italian patient association “Mitocon” for the informatic support. The work of the “Besta” group of Milan was supported by the Pierfranco and Luisa Mariani Foundation Italy, Ricerca 2000; Fondazione Giuseppe Tomasello ONLUS and Fondazione Telethon-Italy grants GGP07019 and GPP10005. The work of the University of Milan group was supported by Associazione Amici del Centro Dino Ferrari, by the Telethon project GTB07001ER, and by a Telethon grant “Network of Genetic Biobanks” no GTB07001.

Conflicts of interest

The authors declare no conflicts of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Michelangelo Mancuso
    • 1
  • Daniele Orsucci
    • 1
  • Corrado Angelini
    • 2
    • 3
  • Enrico Bertini
    • 4
  • Valerio Carelli
    • 5
    • 18
  • Giacomo Pietro Comi
    • 6
  • Alice Donati
    • 17
  • Carlo Minetti
    • 7
  • Maurizio Moggio
    • 8
  • Tiziana Mongini
    • 9
  • Serenella Servidei
    • 10
  • Paola Tonin
    • 11
  • Antonio Toscano
    • 12
  • Graziella Uziel
    • 13
  • Claudio Bruno
    • 7
  • Elena Caldarazzo Ienco
    • 1
  • Massimiliano Filosto
    • 15
  • Costanza Lamperti
    • 14
  • Michela Catteruccia
    • 4
  • Isabella Moroni
    • 13
  • Olimpia Musumeci
    • 12
  • Elena Pegoraro
    • 2
    • 3
  • Dario Ronchi
    • 6
  • Filippo Maria Santorelli
    • 16
  • Donato Sauchelli
    • 10
  • Mauro Scarpelli
    • 11
  • Monica Sciacco
    • 8
  • Maria Lucia Valentino
    • 5
    • 18
  • Liliana Vercelli
    • 9
  • Massimo Zeviani
    • 14
  • Gabriele Siciliano
    • 1
  1. 1.Neurological ClinicUniversity of PisaPisaItaly
  2. 2.Neurological ClinicUniversity of PadovaPaduaItaly
  3. 3.IRCCS S. CamilloVeniceItaly
  4. 4.Laboratory of Molecular MedicineBambino Gesù HospitalRomeItaly
  5. 5.IRCCS Istituto Delle Scienze Neurologiche di BolognaBolognaItaly
  6. 6.Neuroscience Section, Neurology Unit, Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT)IRCCS Foundation Ca’ Granda Ospedale Maggiore Policlinico, University of MilanMilanItaly
  7. 7.Neuropediatric and Muscle Disorders UnitUniversity of Genoa, G. Gaslini InstituteGenoaItaly
  8. 8.Neuromuscular Unit, Dino Ferrari CentreFondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of MilanMilanItaly
  9. 9.Department of NeuroscienceUniversity of TurinTurinItaly
  10. 10.Institute of NeurologyCatholic UniversityRomeItaly
  11. 11.Neurological ClinicUniversity of VeronaVeronaItaly
  12. 12.Department of NeurosciencesUniversity of MessinaMessinaItaly
  13. 13.Child Neurology UnitThe Foundation “Carlo Besta” Institute of Neurology, IRCCSMilanItaly
  14. 14.Unit of Molecular NeurogeneticsThe Foundation “Carlo Besta” Institute of Neurology, IRCCSMilanItaly
  15. 15.Neurological ClinicUniversity Hospital Spedali CiviliBresciaItaly
  16. 16.IRCCS Stella MarisPisaItaly
  17. 17.A. Meyer Children’s HospitalUniversity of FlorenceFlorenceItaly
  18. 18.Department of Biomedical and Neuromotor SciencesUniversity of BolognaBolognaItaly

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