title: Mitochondrial DNA haplogroups do not play a role in the variable phenotypic presentation of the A3243G mutation.
abstract: Thirty-five mitochondrial (mt) DNAs from Spain that harbor the mutation A3243G in association with either MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) syndrome or a wide array of disease phenotypes (ranging from diabetes and deafness to a mixture of chronic progressive external ophthalmoplegic symptoms and strokelike episodes) were studied by use of high-resolution restriction fragment length polymorphism analysis and control-region sequencing. A total of 34 different haplotypes were found, indicating that all instances of the A3243G mutation are probably due to independent mutational events. Haplotypes were distributed into 13 haplogroups whose frequencies were close to those of the general Spanish population. Moreover, there was no statistically significant difference in haplogroup distribution between patients with MELAS and those with disease phenotypes other than MELAS. Overall, these data indicate that the A3243G mutation harbors all the evolutionary features expected from a severely deleterious mtDNA mutation under strong negative selection, and they reveal that European mtDNA backgrounds do not play a substantial role in modulating the mutation's phenotypic expression.
authors.affiliation: Dipartimento di Genetica e Microbiologia, Università di Pavia, Pavia, Italy. torroni@ipvgen.unipv.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Torroni
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Campos
authors.forename: Chiara
authors.initials: C
authors.lastname: Rengo
authors.forename: Daniele
authors.initials: D
authors.lastname: Sellitto
authors.forename: Alessandro
authors.initials: A
authors.lastname: Achilli
authors.forename: Chiara
authors.initials: C
authors.lastname: Magri
authors.forename: Ornella
authors.initials: O
authors.lastname: Semino
authors.forename: Alberto
authors.initials: A
authors.lastname: García
authors.forename: Pilar
authors.initials: P
authors.lastname: Jara
authors.forename: Joaquín
authors.initials: J
authors.lastname: Arenas
authors.forename: Rosaria
authors.initials: R
authors.lastname: Scozzari
mesh_terms: D000328:Adult; D000368:Aged; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D017241:MELAS Syndrome / Q000235:genetics*; D008875:Middle Aged; D008957:Models, Genetic; D020125:Mutation, Missense; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D013030:Spain
chemical_list: D004272:DNA, Mitochondrial