From the Guidelines
Male offspring can develop diseases in mitochondrial inheritance, but they cannot transmit the mitochondrial mutation to their children. Mitochondrial diseases are passed from mother to all her children, regardless of sex, because mitochondrial DNA is inherited exclusively from the mother [ 1 ]. When a mother carries a mitochondrial mutation, both her sons and daughters have an equal chance of inheriting the defective mitochondria. The severity of mitochondrial diseases can vary widely among siblings due to heteroplasmy (different proportions of normal and mutated mitochondria in different cells) [ 1 ].
Some key points to consider in mitochondrial inheritance include:
- Mitochondrial DNA is inherited exclusively from the mother [ 1 ]
- Male offspring can develop the disease, but they cannot transmit the mitochondrial mutation to their children
- The severity of mitochondrial diseases can vary widely among siblings due to heteroplasmy [ 1 ]
- Common mitochondrial disorders that affect males include Leber's hereditary optic neuropathy (LHON), mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), and Leigh syndrome [ 1 ]
In terms of management and counseling, it is essential to consider the unique aspects of mitochondrial inheritance, including the risk of transmission to offspring and the potential for variable expression of the disease [ 1 ]. Genetic counseling plays a crucial role in helping families understand the risks and implications of mitochondrial disease [ 1 ].
From the Research
Mitochondrial DNA Inheritance and Disease Development in Male Offspring
- Mitochondrial diseases are relatively frequent and can be caused by maternally inherited mitochondrial DNA (mtDNA) mutations, with about 15% of cases attributed to this cause 2.
- The severity of the phenotype and the lack of effective treatment make it crucial for couples to prevent the transmission of these mtDNA disorders to their offspring 2.
- Preimplantation genetic diagnosis (PGD) is a viable option for preventing the transmission of mtDNA disorders, allowing for the transfer of embryos with a mutation load below the threshold of clinical expression 2.
- Studies have shown that PGD can provide carriers of mtDNA mutations the opportunity to conceive healthy offspring, including male offspring 2.
- However, the pattern of mitochondrial inheritance is not entirely clear, and there is evidence to suggest that paternal mitochondrial DNA transmission may occur in some cases, although this is not a common phenomenon 3, 4.
- In cases where paternal mtDNA transmission does occur, it may follow an autosomal dominant-like inheritance mode, with biparental mtDNA transmission observed in some families 4.
- The development of disease in male offspring due to mtDNA inheritance is still not fully understood and requires further research to elucidate the underlying mechanisms and to develop effective therapeutic strategies 5.
- It is essential to note that mitochondrial transmission can be distinguished from X-linked transmission by examining sex-specific patterns of disease expression in matrilineally transmitted diseases 6.