The m.3243A>G mitochondrial DNA mutation and related phenotypes. A matter of gender?
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- 作者：Michelangelo Mancuso (1)
Daniele Orsucci (1)
Corrado Angelini (2) (3)
Enrico Bertini (4)
Valerio Carelli (18) (5)
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 (18) (5)
Liliana Vercelli (9)
Massimo Zeviani (14)
Gabriele Siciliano (1) - 关键词：A3243G ; MELAS ; MIDD ; Mitochondrial DNA ; PEO ; Stroke ; like episodes
- 刊名：Journal of Neurology
- 出版年：2014
- 出版时间：March 2014
- 年：2014
- 卷：261
- 期：3
- 页码：504-510
- 全文大小：249 KB
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Daniele Orsucci (1)
Corrado Angelini (2) (3)
Enrico Bertini (4)
Valerio Carelli (18) (5)
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 (18) (5)
Liliana Vercelli (9)
Massimo Zeviani (14)
Gabriele Siciliano (1)
1. Neurological Clinic, University of Pisa, Via Roma 67, 56100, Pisa, Italy
2. Neurological Clinic, University of Padova, Padua, Italy
3. IRCCS S. Camillo, Venice, Italy
4. Laboratory of Molecular Medicine, Bambino Gesù Hospital, Rome, Italy
18. Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
5. IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy
6. Neuroscience Section, Neurology Unit, Dino Ferrari Centre, Department of Pathophysiology and Transplantation (DEPT), IRCCS Foundation Ca-Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
17. A. Meyer Children’s Hospital, University of Florence, Florence, Italy
7. Neuropediatric and Muscle Disorders Unit, University of Genoa, G. Gaslini Institute, Genoa, Italy
8. Neuromuscular Unit, Dino Ferrari Centre, Fondazione IRCCS Ca-Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
9. Department of Neuroscience, University of Turin, Turin, Italy
10. Institute of Neurology, Catholic University, Rome, Italy
11. Neurological Clinic, University of Verona, Verona, Italy
12. Department of Neurosciences, University of Messina, Messina, Italy
13. Child Neurology Unit, The Foundation “Carlo Besta-Institute of Neurology, IRCCS, Milan, Italy
15. Neurological Clinic, University Hospital Spedali Civili, Brescia, Italy
14. Unit of Molecular Neurogenetics, The Foundation “Carlo Besta-Institute of Neurology, IRCCS, Milan, Italy
16. IRCCS Stella Maris, Pisa, Italy - ISSN：1432-1459
文摘
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.