title: Pathogenic mitochondrial DNA mutations are common in the general population.
abstract: Mitochondrial DNA (mtDNA) mutations are a major cause of genetic disease, but their prevalence in the general population is not known. We determined the frequency of ten mitochondrial point mutations in 3168 neonatal-cord-blood samples from sequential live births, analyzing matched maternal-blood samples to estimate the de novo mutation rate. mtDNA mutations were detected in 15 offspring (0.54%, 95% CI = 0.30-0.89%). Of these live births, 0.00107% (95% CI = 0.00087-0.0127) harbored a mutation not detected in the mother's blood, providing an estimate of the de novo mutation rate. The most common mutation was m.3243A-->G. m.14484T-->C was only found on sub-branches of mtDNA haplogroup J. In conclusion, at least one in 200 healthy humans harbors a pathogenic mtDNA mutation that potentially causes disease in the offspring of female carriers. The exclusive detection of m.14484T-->C on haplogroup J implicates the background mtDNA haplotype in mutagenesis. These findings emphasize the importance of developing new approaches to prevent transmission.
authors.affiliation: Mitochondrial Research Group, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Hannah R
authors.initials: HR
authors.lastname: Elliott
authors.forename: David C
authors.initials: DC
authors.lastname: Samuels
authors.forename: James A
authors.initials: JA
authors.lastname: Eden
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Relton
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
mesh_terms: D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005312:Fetal Blood; D005828:Genetics, Population; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics; D008957:Models, Genetic; D015233:Models, Statistical; D009154:Mutation; D015995:Prevalence
chemical_list: D004272:DNA, Mitochondrial