Young: Medical Genetics 
Multiple Choice QuestionsYoung: Medical Genetics
Your family tree should resemble the one shown above. Clearly there is a striking history of muscle weakness and neurological disorder in the mother’s side of the family. It is notable that transmission has occurred exclusively through females with both males and females affected. This could represent autosomal dominant inheritance with reduced penetrance (page 72), but there is no example of male to male transmission. X-linked transmission is another possibility. However, it cannot be X-linked recessive as several females are affected, and X-linked dominant inheritance is unlikely as neither of the affected males has transmitted the condition to his daughters.
This leaves mitochondrial inheritance as the most probable mode of transmission (page 86). Mitochondrial disorders tend to preferentially involve organs such as brain and muscle, which have high energy requirements (page 216), and they can sometimes be quite variable in severity within a family depending upon the proportion of mitochondria which harbour the mutation. (If the mutation is present in all mitochondria this is referred to as homoplasmy: if present in only some of the mitochondria the term heteroplasmy is used). The fact that the familial pattern of involvement is suggestive of mitochondrial transmission would prompt investigations for an underlying mutation in mitochondrial DNA.
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