A 22-year-old man experiences painless progressive loss of central vision in both eyes over several months. Fundus examination shows peripapillary telangiectatic microangiopathy. Family history reveals his mother's brother and his sister's son have similar visual loss, while no affected individuals appear among his father's relatives. This inheritance pattern is best explained by:
- A Mitochondrial DNA mutation transmitted by the ovum, showing heteroplasmy-dependent expression ✓
- B X-linked dominant mutation lethal in homozygous females
- C Autosomal dominant gene with sex-limited expression
- D Genomic imprinting causing paternal allele silencing
Explanation
Leber hereditary optic neuropathy arises from point mutations in mitochondrial DNA, most commonly the m.11778G>A mutation in MT-ND4. Because mitochondria are inherited almost exclusively through the ovum, transmission is strictly maternal, matching the pedigree described. Variable penetrance and severity reflect heteroplasmy, the proportion of mutant versus wild-type mitochondrial genomes in retinal ganglion cells. X-linked dominant traits would affect fathers' daughters equally, sex-limited autosomal dominance would show male-to-male transmission, and imprinting disorders do not follow strict maternal-only vertical transmission through multiple generations.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.