Paternal Inheritance of Mitochondrial Myopathy Gene



Paternal Inheritance of Mitochondrial Myopathy Gene

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





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