Spinal Muscle Atrophy is characterized by the loss of movement as a result of the loss of motor neurons in the spinal cord. This ailment cannot be cured, but treatments are available to improve the quality of life for the patient. Walking, sitting up straight, or even crawling can become difficult for the sufferer. The severity of this disease makes it essential to look for its causes.
Types 1-4
These forms are caused by a mutation in the SMN1 gene present in chromosome 5. It should be noted that people have two SMN1 genes present, one on each chromosome 5. This mutation leads to a deficiency in the motor neuron protein called survival motor neuron (SMN). This protein is important to carry out normal motor neuron functions. Another cause is a mutation in the UBE1 gene present in the X chromosome. This causes X-linked spinal muscle atrophy. This UBE1 gene carries information and instructions for ubiquitin, activating enzyme 1. This helps in making proteins for destruction by attaching a molecular tag to them. Mutation in the cytoplasmic dynein 1 heavy chain 1 (DYNC1H1) gene on chromosome 14 also causes another rare form of SMA which is SMA-LED.
What causes such variations in symptoms?
The SMN1 gene normally produces fully functional and full-length SMN proteins. However, when it gets mutated, insufficient levels or SMN proteins are produced and this variation causes the difference in severity of the disease. A neighboring gene present on chromosome 5, known as SMN2, also produces SMN protein. It should be noted that most of the proteins are created from instructions carried by the SMN2 genes that are not functional. Only a small part is functional. There can be multiple such copies of the SMN2 gene. Actually, in the chromosome 5 form of SMA, the more SMN2 genes a person carries, more of SMN protein is available and as a result, the milder the disease is. Genetic testing can be done to know the amount of SMN2 gene a person has. This can also predict how much SMA protein will be produced.
Disease modifiers
Disease modifiers do not cause the disease, but they affect the severity and onset of the disease by influencing biological pathways. Plastic 3 protein and the ZPR1 protein levels are modifiers of SMN related SMA.
Inheritance patterns of spinal muscle atrophy
The inheritance pattern is called spinal muscle atrophy recessive. Here, the autosomes are actually numbered chromosomes, which refers to all chromosomes except X and Y (which determine gender). The disease requires two gene flaws, generally from one parent each. If both parents are carriers of the chromosome 5 gene mutation, then the risk of having a child affected by spinal muscle atrophy is 25%.
X-linked SMA
Here, it is inherited via the X chromosome. Females have two X chromosomes. Those with the gene deficiency on one of the X-chromosome are seen as carriers of the X-linked disease. Males lack the protection of a second X, which can protect them from the full severity of the disease.
DYNC1H1 gene
Present on chromosome 14, this form of the disease is dominantly inherited, which means that one DYNC1H1 gene mutation is inherited from just one parent and is enough to cause the disease.
Genetic testing can be used to track the severity of the disease as it helps in beginning early treatment.
