title: The m.3243A>G mitochondrial DNA mutation and related phenotypes. A matter of gender?
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.
authors.affiliation: Neurological Clinic, University of Pisa, Via Roma 67, 56100, Pisa, Italy, mancusomichelangelo@gmail.com.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Mancuso
authors.forename: Daniele
authors.initials: D
authors.lastname: Orsucci
authors.forename: Corrado
authors.initials: C
authors.lastname: Angelini
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Valerio
authors.initials: V
authors.lastname: Carelli
authors.forename: Giacomo Pietro
authors.initials: GP
authors.lastname: Comi
authors.forename: Alice
authors.initials: A
authors.lastname: Donati
authors.forename: Carlo
authors.initials: C
authors.lastname: Minetti
authors.forename: Maurizio
authors.initials: M
authors.lastname: Moggio
authors.forename: Tiziana
authors.initials: T
authors.lastname: Mongini
authors.forename: Serenella
authors.initials: S
authors.lastname: Servidei
authors.forename: Paola
authors.initials: P
authors.lastname: Tonin
authors.forename: Antonio
authors.initials: A
authors.lastname: Toscano
authors.forename: Graziella
authors.initials: G
authors.lastname: Uziel
authors.forename: Claudio
authors.initials: C
authors.lastname: Bruno
authors.forename: Elena Caldarazzo
authors.initials: EC
authors.lastname: Ienco
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Filosto
authors.forename: Costanza
authors.initials: C
authors.lastname: Lamperti
authors.forename: Michela
authors.initials: M
authors.lastname: Catteruccia
authors.forename: Isabella
authors.initials: I
authors.lastname: Moroni
authors.forename: Olimpia
authors.initials: O
authors.lastname: Musumeci
authors.forename: Elena
authors.initials: E
authors.lastname: Pegoraro
authors.forename: Dario
authors.initials: D
authors.lastname: Ronchi
authors.forename: Filippo Maria
authors.initials: FM
authors.lastname: Santorelli
authors.forename: Donato
authors.initials: D
authors.lastname: Sauchelli
authors.forename: Mauro
authors.initials: M
authors.lastname: Scarpelli
authors.forename: Monica
authors.initials: M
authors.lastname: Sciacco
authors.forename: Maria Lucia
authors.initials: ML
authors.lastname: Valentino
authors.forename: Liliana
authors.initials: L
authors.lastname: Vercelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Zeviani
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000235:genetics; D030541:Databases, Genetic; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007558:Italy; D017241:MELAS Syndrome / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D017237:Mitochondrial Encephalomyopathies / Q000145:classification / Q000235:genetics / Q000503:physiopathology*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012189:Retrospective Studies; D012737:Sex Factors; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial