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 his
father.
"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 respiratory function.
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. 2002;347(8):576-579,
609-611
Reviewed by Gary D. Vogin, MD
