As we reported previously, a team of researchers identified mutations in a gene called SMCHD1 which can cause FSH type 2 – a rare form of the condition affecting around 5% of people with FSH.
Researchers have now discovered that the same gene may affect the severity of FSH type 1 – the most common form of the condition caused by a deletion in the DNA on chromosome 4. This deletion allows muscle cells to produce a protein called DUX4 which is not normally made in adult muscle cells. DUX4 is a transcription factor – a molecular switch – which can turn other genes on and off and this eventually leads to the death of muscle cells.
Although scientists believe that the size of the deletion on chromosome 4 is linked to the severity of the condition, variation in disease severity is seen in people with similar deletions. This suggests other factors may play a role and researchers have shown that SMCHD1 can play a role as a modifier gene.
Modifier genes are those which may not cause a condition but can affect the severity of the symptoms. Mutations in SMCHD1 are also thought to allow DUX4 protein to be produced. This is the same pathway which deletions on chromosome 4 activate, and since both mutations affect the same biological pathway, it is possible their effects may be additive, something researchers are now investigating further.
What this means for patients
The discovery of a modifier gene may help researchers and clinicians to help families to understand the risk of passing the condition on to their children. It may also allow families to consider the option of using new technology when planning to have children. Knowing the genetic diagnosis allows clinicians to gather more precise information on how the disease might progress so affected families can plan for the future and gain access to appropriate care.
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