For certain individuals with ALS, the condition is thought to be caused by abnormal superoxide dismutase 1 (SOD1) protein. Variants in the SOD1 gene are thought to cause abnormal SOD1 protein to be made, which is likely harmful to cells and possibly causes nerve cells to break down and die. There are many different kinds of SOD1 gene variants.1 The ATLAS Study is studying some, but not all, SOD1 gene variants.
As you may know, ALS is a rare neurodegenerative disease in which the nerve cells that control muscles (also known as motor neurons) break down and die over time. This results in progressive loss of muscle mass, strength, and function.
Everyone has two copies of most genes, including the SOD1 gene: one copy that we inherit from our mother, and one copy that we inherit from our father. If an individual has a SOD1 gene variant, that typically means they have one abnormal copy of the SOD1 gene and one normal copy. Having one abnormal copy of the SOD1 gene may be enough to cause an increased risk of developing ALS. This is called autosomal dominant inheritance (see graphic below), and it’s how the majority of SOD1-ALS is inherited. In other words, the abnormal copy of the SOD1 gene dominates over the normal copy; therefore, having only one abnormal copy may cause an increased risk for ALS.
When an individual has children, they pass on one copy of each of their genes to each child. This means that if a parent has a single SOD1 gene variant, there is a 50% chance that the SOD1 gene variant will be passed down to each child. Alternatively, there is a 50% chance that the normal copy of the SOD1 gene will be passed down to each child. If an individual does not inherit the SOD1 gene variant from their parent, that means they will not pass on the SOD1 gene variant to their children either. Men and women have equal chances of not only inheriting a SOD1 gene variant from their parents but also passing it on to their children. In rare cases, de novo variants in the SOD1 gene have been reported, meaning that the variant occurred for the first time in that individual and was not inherited from a parent.4