genetics
Last reviewed 09/2021
KSS is usually sporadic, and is caused by deletion or insertion mutations in the mitochondrial DNA:
The deletions:
- never include the origins of DNA replication
- up to 50% of cases are caused by a specific 5 kb deletion
- each patient has a single mutant form of mtDNA because the mutation occurs early in development
- the proportion of mutant mitochondria increases with time because the smaller genome replicates quicker
The insertions:
- often the origins of DNA replication are duplicated; such mutant mtDNA accumulates because it is replicated twice as often
Rarely, KSS is inherited as an autosomal dominant trait. In these patients there are a wide variety of mtDNA deletions. It is thought that this form of the disease results from a defective nuclear gene which is involved in mtDNA replication.