An international team of researchers from the Netherlands, France and the USA has identified mutations in a gene called SMCHD1 which can cause FSH type 2. This discovery may help researchers to develop genetic tests and lead to a greater understanding of the underlying changes that are involved in the condition. In the long term it could help researchers to develop therapies in the future.
Approximately 95% of people diagnosed with FSH muscular dystrophy have FSH type 1. This condition is caused by a deletion (or contraction) in a part of chromosome 4 called the D4Z4 region. When this mutation is found near a piece of DNA called a permissive allele it can lead to abnormal production of a protein called DUX4 in the muscles. DUX4 controls how cells read many other genes, and so the production of the DUX4 protein alters the proteins produced in muscle cells and will eventually cause them to die.
Around five percent of people with FSH are thought to have FSH type 2. People with FSH type 2 experience similar symptoms to people with FSH type 1 but have no deletion in the D4Z4 region of chromosome 4. Until now, people with FSH type 2 could not be given a precise genetic diagnosis. Now, an international team of researchers from the Netherlands, France and the USA has identified mutations that can cause FSH type 2.
The researchers studied the DNA of 14 people with FSH type 2 and used a combination of techniques, including next generation sequencing, to look for mutations that might cause the disease. Mutations were identified in a gene called SMCHD1 in all 14 people. However, because only few people were included in the study, it must be noted that mutations in other genes could also cause FSH type 2.
The gene carries the genetic blueprint for a protein called Structural Maintenance of Chromosomes Flexible Hinge containing 1, or SMCHD1 for short. This protein helps cells to control which genes are active, and one of the genes it helps to control is DUX4. Mutations in the SMCHD1 gene can therefore lead to the abnormal production of DUX4 which can lead to FSH muscular dystrophy.
The discovery of a mutation which causes FSH type 2 may help researchers to develop genetic tests for people with this condition. A precise genetic diagnosis is vital for helping 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.
In the longer term, this research will lead to a greater understanding of the biological mechanisms that are involved in FSH type 2. Identification of the SMCHD1 gene highlights a new mechanism by which FSH can be caused and may help researchers to develop therapies in the future.
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