TABLE 2.
Inheritance patterns of primary mitochondrial disease.
| INHERITANCE PATTERN: | MATERNAL | AUTOSOMAL RECESSIVE | AUTOSOMAL DOMINANT | X-LINKED | SPORADIC |
|---|---|---|---|---|---|
| Disease examples: | mtDNA point mutations (e.g., MELAS, MERRF, NARP, some causes of Leigh syndrome) |
mtDNA depletion disorders caused by nuclear gene mutations (e.g., POLG1 or DGUOK) nDNA mutations in OXPHOS subunit or assembly genes |
POLG1-related diseases (e.g., progressive external ophthalmoplegia or parkinsonism) |
One cause of OXPHOS Complex I deficiency Pyruvate dehydrogenase deficiency (e.g., PDHA1) Barth syndrome |
Persistent lactic acidemia of unclear etiology Muscle biopsy abnormality of unclear etiology |
| Recurrence risk to full siblings: | • 1-4% if asymptomatic mother • < 50% risk if symptomatic mother |
25% | 50% if affected parent <1% if asymptomatic parent based on risk of gonadal mosaicism |
If carrier mother: 50% for brothers to be affected; 50% for sisters to be carriers/affected** If de novo: <1% for brothers to be affected or sisters to be carriers** |
Uncertain |
| Recurrence risk to half-maternal sibs: | Same as above | None* | Uncertain | ||
| Recurrence risk to half-paternal sibs: | None | •None for boys • 50% risk girls will be carriers** |
Uncertain | ||
| Recurrence risk to offspring of affected females: | Up to 50% for both sons and daughters | None* All children will be carriers |
50% for both sons and daughters | • 50% for sons • 50% for daughters to be carriers/affected** |
Uncertain |
| Recurrence risk to offspring of affected males: | None | • None for sons • 50% risk daughters will be carriers/affected** |
Uncertain |
*
Assuming low carrier frequency in population such that partner is not a carrier for any mutation in causative gene.
**
Patterns of x-inactivation determine whether females are asymptomatic carriers or affected with x-linked conditions.
nDNA, nuclear DNA; mtDNA, mitochondrial DNA; MELAS, mitochondrial encephalomyopathy, lactic acidosis, and stroke; MERRF, myoclonic epilepsy and ragged red fibers; NARP, neurogenic ataxia and retinitis pigmentosa; OXPHOS, oxidative phosphorylation.