Correspondence
Paternal Inheritance of Mitochondrial DNA
N Engl J Med 2002; 347:2081-2082December 19, 2002
- Article
To the Editor:
Schwartz and Vissing (Aug. 22 issue)1 describe a patient in whom paternal inheritance of mitochondrial DNA (mtDNA) was confirmed. However, the notion of paternal inheritance of mtDNA has been raised before — in one instance, in the Journal.2 In that 1983 report, 30 families were studied for transmission of mitochondrial cytopathy. Maternal inheritance occurred in the majority of cases, but three cases showed evidence of paternal transmission. Although the authors recognized this possibility, it may have been that the dominant view at that time3 prompted them to provide some alternative explanations as well, and therefore, they did not fully recognize the potential for paternal inheritance. Time and again, we are reminded that what we teach our students today may not necessarily be valid later. This lesson should also be coupled with an admonition to question vigorously data that appear to lie “outside of the box.”
3 ReferencesAlvar W. Gustafson, Ph.D.
Tufts University School of Medicine, Boston, MA 02111
al.gustafson@tufts. edu 1
Schwartz M ,Vissing J . Paternal inheritance of mitochondrial DNA. N Engl J Med 2002;347:576-580
Full Text | Web of Science | Medline2
Egger J ,Wilson J . Mitochondrial inheritance in a mitochondrially mediated disease. N Engl J Med 1983;309:142-146
Full Text | Web of Science | Medline3
Giles RE ,Blanc H ,Cann HM ,Wallace DC . Maternal inheritance of human mitochondrial DNA. Proc Natl Acad Sci U S A 1980;77:6715-6719
CrossRef | Web of Science | Medline
To the Editor:
Schwartz and Vissing note that written consent was not required by the institutional review board because the genetic studies were considered to be part of clinical care. One wonders why this was so. For the patient, identification of a mitochondrial base-pair deletion could not be considered to be part of clinical care, since reparative gene therapy for such a deletion is not feasible. For the parents, the sister, and the paternal uncle, mitochondrial haplotype analysis could not be considered to be clinical care, since none had symptoms of skeletal or cardiac myopathy, and even if they had, they would not have benefited from such testing. The benefit here was the generation of new knowledge, and as such, it would have to be weighed by each subject against the potential loss of privacy from having the mitochondrial genome sequenced.1 Such a deliberation would require an informed-consent process that explicitly acknowledged the lack of direct benefit and that clearly described the risk of a loss of confidentiality. At our medical center, such a study would have required approval by a convened institutional review board and written informed consent.
1 ReferencesPaul S. Heckerling, M.D.
University of Illinois at Chicago, Chicago, IL 60612
pshecker@uic.edu 1
Fuller BP ,Kahn MJ ,Barr PA , et al. Privacy in genetics research. Science 1999;285:1359-1361
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Dr. Gustafson states that the possibility of paternal inheritance of mtDNA has been raised before. It is true that it has been speculated on multiple times,1,2 but it has not previously been proved to occur in humans. We believe that the occurrence of a pathogenic mtDNA mutation is necessary for the accumulation of paternal mtDNA. Only further investigation of sporadic cases in persons harboring mtDNA mutations can determine the frequency of this phenomenon.
Dr. Heckerling's concern that approval by an institutional review board and written consent were not obtained in our study was also raised during the review process for our article. Before acceptance, the paper was submitted to the central institutional review board in Copenhagen; this board approved the protocol and did not request any written consent procedure. Obviously, consent procedures differ among countries.
We disagree that “identification of a mitochondrial base-pair deletion could not be considered to be part of clinical care.” Patients with mitochondrial myopathy are often given a misdiagnosis of being “terribly out of shape” or of having poor effort and motivation. Extensive pulmonary and cardiac investigations are often performed, particularly when muscle is the only affected organ, as in our patient. Our patient had had multiple investigations performed since childhood. When a specific diagnosis is made, not only are patients spared further, unnecessary testing, but often the diagnosis provides answers to many of their questions and helps them to explain their condition to other people.
In our experience, patients with muscle diseases generally want molecular characterization of their conditions. In addition, the detection of mutations in patients with mitochondrial myopathy has prognostic implications, since the outcome varies according to the load of mutation in different tissues. This information was clinically relevant not only for our patient, but also for his sister, who wanted to know whether she harbored the mutation before she became pregnant. In our opinion, the failure to provide genetic testing for a capable person who requests such testing and who understands the pros and cons is nihilistic.
2 ReferencesJohn Vissing, M.D., Ph.D.
Marianne Schwartz, Ph.D.
University Hospital Rigshospitalet, DK-2100 Copenhagen, Denmark
schwartz@rh.dk 1
Ankel-Simons F ,Cummins JM . Misconception about mitochondria and mammalian fertilization: implications for theories on human evolution. Proc Natl Acad Sci U S A 1996;93:13859-13863
CrossRef | Web of Science | Medline2
Eyre-Walker A ,Smith NH ,Smith JM . How clonal are human mitochondria? Proc R Soc Lond B Biol Sci 1999;266:477-483
CrossRef | Web of Science
- Citing Articles (3)
Citing Articles
1
Marianne Schwartz, John Vissing. (2004) No evidence for paternal inheritance of mtDNA in patients with sporadic mtDNA mutations. Journal of the Neurological Sciences 218:1-2, 99-101
CrossRef2
Robert W. Taylor, Martina T. McDonnell, Emma L. Blakely, Patrick F. Chinnery, Geoffrey A. Taylor, Neil Howell, Massimo Zeviani, Egill Briem, Franco Carrara, Douglass M. Turnbull. (2003) Genotypes from patients indicate no paternal mitochondrial DNA contribution. Annals of Neurology 54:4, 521-524
CrossRef3
Marianne Schwartz, John Vissing. (2003) New patterns of inheritance in mitochondrial disease. Biochemical and Biophysical Research Communications 310:2, 247-251
CrossRef
