Mol. Hum. Reprod. Advance Access published online on March 18, 2009
Molecular Human Reproduction, doi:10.1093/molehr/gap021
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Do mitochondrial mutations cause recurrent miscarriage?
1Folkhälsan Institute of Genetics, University of Helsinki, P.O. Box 63, 00014 Helsinki, Finland 2Research Program of Molecular Neurology, Biomedicum-Helsinki, University of Helsinki, Finland 3Department of Obstetrics and Gynecology, Helsinki University Central Hospital, P.O. Box 140, 00029 HUS, Helsinki, Finland 4Pathology Clinic, Molecular Pathology, Rikshospitalet Medical Center, N-0027 Oslo, Norway 5Department of Neurology, Helsinki University Central Hospital, P.O.Box 63, 00014 University of Helsinki, Finland 6Department of Clinical Genetics, Helsinki University Central Hospital, P.O. Box 140, 00029 HUS, Helsinki, Finland
* Corresponding author: Milja Kaare, Folkhälsan Institute of Genetics, BiomedicumHelsinki, P.O. Box 63, University of Helsinki, FIN-00014,Helsinki, Finland. E-mail: milja.kaare{at}helsinki.fi, Telephone: +358 919125082, Fax: +358 91925073
The cause of recurrent miscarriage (RM) can be identified in 
50% of cases, while in others, unknown genetic factors are actively being sought. As mitochondrial functions, and therefore also the mitochondrial genome (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 dHPLC, a sensitive method which 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 to that in the mother. We conclude that our sensitive methodology revealed a higher frequency of samples with heteroplasmic variations than expected in both women with 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.