Causes of Spinal Muscular Atrophies
The 5q chromosome contains two copies of the survival neuron gene 1 (SMN1). This is the most common cause of spinal muscular atrophy. The SMN1 gene produces the survival motor neuron protein (SMN) that is necessary to maintain motor neurons’ normal functions and health. Insufficient levels of SMN proteins can cause spinal muscular atrophy in some individuals. SMN protein in low amounts causes motor neuron loss in the spinal chord, resulting in wasting of skeletal muscles and weakness. The muscles of the upper leg, arm, and trunk are more affected by spinal muscular atrophy than the muscles in the hands and feet.
Multiple changes or mutations of the same gene cause several types of spinal muscle atrophy. Changes in genes, such as those on chromosomes 20, 14, and 9, can cause less common forms of spinal muscular atrophy. The severity of the muscle weakness and age of onset are two factors that determine which type of spinal muscular is. There is still a lot of overlap between the different types of SMN.
Genes SMN
Spinal muscular atrophy is usually autosomal recessive, meaning that the person who develops SMN carries both mutated genes. Each patient with SMN will inherit both mutated genes from their parents. In rare cases, SMN can be caused by mutations of the UBA1 genes. People who have only one mutated chromosome do not show any symptoms of disorder, but they are carriers. SMN is a recessive autosomal disorder. This means that more than one member of the family may be affected.
Normal conditions produce full-length and fully functional SMN proteins that are necessary for neurological and muscular functions. Insufficient SMN protein levels are produced when the SMN1 gene suffers from mutations. A mutation on chromosome 5 also affects the SMN2 genes. The SMN2 gene produces proteins in very small amounts and they are non-functional. Moreover, only 10-15% of the SMN protein are functional.
The SMN2 gene is present in multiple copies throughout the body. SMN2 gene copies can range from zero to eight in an individual. The more copies of SMN2 gene in the body the greater the amount of functional SMN proteins available in the system. This results in milder disease symptoms. The severity of a disease is also dependent on the severity and onset of various biological pathways. The biological modifiers, such as ZPR1 and plastin 3 proteins, indicate the severity or onset of the disease.
