151. The m.3243A>G mitochondrial DNA mutation and related phenotypes. A matter of gender?
- Author
-
Olimpia Musumeci, Dario Ronchi, Graziella Uziel, Tiziana Mongini, Elena Caldarazzo Ienco, Enrico Bertini, Alice Donati, Corrado Angelini, Michela Catteruccia, Antonio Toscano, Paola Tonin, Filippo M. Santorelli, Massimo Zeviani, Mauro Scarpelli, Elena Pegoraro, Gabriele Siciliano, Valerio Carelli, Daniele Orsucci, Maurizio Moggio, M. Sciacco, Serenella Servidei, Giacomo P. Comi, Massimiliano Filosto, Donato Sauchelli, Costanza Lamperti, Liliana Vercelli, Michelangelo Mancuso, Maria Lucia Valentino, Carlo Minetti, Isabella Moroni, Claudio Bruno, Mancuso, M., Orsucci, D., Angelini, C., Bertini, E., Carelli, V., Comi, G.P., Donati, A., Minetti, C., Moggio, M., Mongini, T., Servidei, S., Tonin, P., Toscano, A., Uziel, G., Bruno, C., Ienco, E.C., Filosto, M., Lamperti, C., Catteruccia, M., Moroni, I., Musumeci, O., Pegoraro, E., Ronchi, D., Santorelli, F.M., Sauchelli, D., Scarpelli, M., Sciacco, M., Valentino, M.L., Vercelli, L., Zeviani, M., and Siciliano, G.
- Subjects
Male ,MELAS syndrome ,Bioinformatics ,G+mutation%22">mitochondrial m.3243A>G mutation ,MIDD ,Genotype ,Databases, Genetic ,MELAS Syndrome ,Child ,Genetics ,mtDNA ,Medicine (all) ,Stroke-like episodes ,Middle Aged ,Mitochondrial DNA ,Mitochondrial ,Settore MED/26 - NEUROLOGIA ,A3243G ,mitochondrial DNA ,PEO ,stroke-like episodes ,Phenotype ,phenotypic ,Italy ,Neurology ,Lactic acidosis ,Child, Preschool ,Mutation (genetic algorithm) ,MELAS ,Female ,medicine.symptom ,Adult ,mitochondrial encephalopathy with lactic acidosis and stroke-like episode ,Heterozygote ,G+"MELAS%22">m.3243A>G "MELAS ,Adolescent ,Hearing loss ,Mitochondrial disease ,Biology ,DNA, Mitochondrial ,Databases ,Young Adult ,Sex Factors ,Genetic ,Mitochondrial Encephalomyopathies ,medicine ,Humans ,Aged ,Infant ,Mutation ,Retrospective Studies ,Neurology (clinical) ,Preschool ,DNA ,medicine.disease - 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. © 2013 Springer-Verlag Berlin Heidelberg.
- Published
- 2014