Aug. 23, 2002 — A case report in the Aug.
22 issue of the New England Journal of Medicine
challenges the dogma that mitochondrial DNA (mtDNA) is
maternally inherited; it describes a man with a
mitochondrial myopathy in which the aberrant gene came from
"The present findings suggest that
investigation of paternal mtDNA inheritance may be warranted
in cases with sporadic mitochondrial mutations," write
Marianne Schwartz, PhD, and John Vissing, MD, PhD, from
University Hospital in Copenhagen, Denmark.
This patient was 28 years old with
severe, lifelong exercise intolerance associated with lactic
acidosis. He had no muscle atrophy or weakness. Muscle
biopsy revealed that 15% of fibers were of the ragged-red
type, consistent with abnormal mitochondria with impaired
Biochemical and DNA analysis suggested
an isolated deficiency of the mitochondrial enzyme complex 1
of the respiratory chain in muscle, caused by a novel 2-bp
mtDNA deletion in the ND2 gene. The mtDNA carrying the
mutation was paternal in origin, and accounted for 90% of
the patient's muscle mtDNA.
"The underlying mechanism responsible
for the elimination of sperm mtDNA in normal embryos is not
well understood," the authors write. "We speculate that the
process in some cases may be defective, allowing sperm
mitochondria to survive and giving those with a selective
advantage the possibility of prevailing in certain tissues."
In an accompanying editorial, R.
Sanders Williams, MD, from Duke University Medical Center in
Durham, North Carolina, notes the impossibility of
estimating the frequency of paternal inheritance of mtDNA in
humans. He recommends accommodating the possibility of
paternal inheritance of mtDNA in statistical models that
analyze sequence variations in mtDNA.
"The interpretation of inheritance
patterns in other kindreds thought to have mitochondrial
disease should not be based on the dogmatic assumption of
absolute maternal inheritance of mtDNA," he writes. "The
unusual case described by Schwartz and Vissing is more than
a mere curiosity."
N Engl J Med.
Reviewed by Gary D. Vogin, MD