Mitochondrial DNA is transmitted exclusively maternally in humans. A woman has MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes) from an MT-TL1 mutation. What is the probability that her son will transmit this disease to his children?
- A 50% — autosomal dominant-like transmission
- B 0% — paternal mitochondria are eliminated after fertilisation; sons cannot transmit mtDNA mutations ✓
- C 25% — autosomal recessive inheritance
- D 100% — all children of an affected son will inherit the mutation
Explanation
Mitochondrial DNA is maternally inherited because the egg contains ~100,000 mitochondria while the sperm contributes only ~100 mitochondria, and paternal mitochondria are selectively eliminated in the fertilised egg by autophagy (mitophagy) tagged by ubiquitin. Therefore, even if an affected mother transmits the mutation to her son, that son's children will not inherit it from him — he cannot pass on his (or anyone's) mitochondria. All children of the affected woman, regardless of sex, have risk of inheriting the mutation (risk depends on heteroplasmy level). Sons and daughters of the affected woman's daughters are at risk; sons' children are not.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.