Mol. Hum. Reprod. Advance Access originally published online on March 18, 2009
Molecular Human Reproduction 2009 15(5):295-300; doi:10.1093/molehr/gap021
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Do mitochondrial mutations cause recurrent miscarriage?
1 Folkhälsan Institute of Genetics, University of Helsinki, PO Box 63, FIN-00014 Helsinki, Finland 2Research Program of Molecular Neurology, Biomedicum-Helsinki, University of Helsinki, Helsinki, Finland 3Department of Obstetrics and Gynecology, Helsinki University Central Hospital, PO Box 140, 00029 HUS Helsinki, Finland 4Pathology Clinic, Molecular Pathology, Rikshospitalet Medical Center, N-0027 Oslo, Norway 5Department of Neurology, Helsinki University Central Hospital, University of Helsinki, PO Box 63, 00014 Helsinki, Finland 6Department of Clinical Genetics, Helsinki University Central Hospital, PO Box 140, 00029 HUS Helsinki, Finland
7 Correspondence address. Tel: +358-919125082; Fax: +358-91925073; E-mail: milja.kaare{at}helsinki.fi
The cause of recurrent miscarriage (RM) can be identified in 
50% of cases, whereas in others, unknown genetic factors are actively being sought. As mitochondrial functions, and therefore also the mitochondrial genome [mitochondrial DNA (mtDNA)], have an important role in human development, through ATP production and participation in apoptosis, we aimed to study the role of mtDNA variations in RM. We screened 48 women with RM and 48 age-matched control women for heteroplasmic mitochondrial mutations using denaturing high performance liquid chromatography, a sensitive method that can detect 5% heteroplasmy. As a result, we detected a heteroplasmic mtDNA variation in 13 RM women (27%) and in 9 control women (19%). Seven synonymous and five non-synonymous changes were detected within coding regions. In addition, seven heteroplasmic variations were detected within the non-coding control region. We were also able to show the presence of the variations in eight placental samples from three heteroplasmic women. In three of these cases, the proportion of variant mtDNA was higher in the placenta compared with that in the mother. We conclude that our sensitive methodology revealed a higher frequency of samples with heteroplasmic variations than expected in women with both RM and controls. However, no apparent increased frequency of heteroplasmic mtDNA variations or amounts of aberrant mtDNA was detected in the RM group. In addition, none of the detected variations were previously known to be pathogenic and therefore they are an unlikely cause of miscarriage.
Key words: DHPLC/mitochondrial DNA variations/recurrent miscarriage
Submitted on December 9, 2008; resubmitted on March 9, 2009; accepted on March 12, 2009.