Mosaic Mutations May Cause Spina Bifida

In the past, researchers have questioned the exact cause of spina bifida, a neural tube defect in which the spine does not fully close around the developing spinal cord nerves. Some have believed the cause to be a mix of hereditary and environmental factors; others linked folic acid deficiency to this condition. However, according to Medical XPress, new research suggests that mosaic mutations, a type of genetic mutation not inherited from either parent, could cause spina bifida. Read the full study findings published in Nature Communications.

Mosaic Mutations

So what exactly are mosaic mutations? According to an article published in Current Oncology, mosaic mutations:

[occur] at some point after the zygote is created. In general, the later in embryonic development that the mutation occurs, the more restricted in distribution the resulting phenotype is, because the cells derived from a mutated founding cell all carry its mutation.

In short, mosaic mutations occur during fetal development. However, these mutations are not inherited from parents but instead occur randomly. While some of these mutations may cause health issues, others will not. Alternately, some mosaic mutations are protective against disease while others cause disease. Researchers refer to mosaic mutations, or having mosaic mutations, as mosaicism.

The Research

Researchers at the University College of London (UCL) Great Ormond Street Institute of Child Health wanted to understand how mosaic mutations alter cell function and cause birth defects. In addition to learning more about these mutations, researchers hoped to also determine how and why mosaic mutations may occur. However, additional research still needs to be performed to come up with a concrete answer.

In their experimental research, UCL researchers created a mutation to inactivate the Vangl2 gene in mouse embryos. Normally, Vangl2 helps tell cells their direction within a tissue and informs how they interact with the cells around them. However, common issues in the cellular signaling pathway, which Vangl2 is part of, have been previously linked to neural tube defects. Additionally, mosaic mutations in this pathway were found in 15% of human infants with spina bifida in a previous study.

When they created a Vangl2 mutation, researchers discovered that the mutation highly affected cell function. When Vangl2 mutations occurred in 16% of developing spinal cord cells, the mice embryos developed spina bifida. In fact, researchers discovered that the mutated cells were extremely powerful and had wide-reaching effects.

Although future research is needed to better understand how to potentially identify these mutations, and treat them, this does offer amazing insight into the power of genetics in regards to health and fetal development.

Spina Bifida

The aptly named spina bifida, which means “cleft spine,” occurs when the neural tube fails to close during the beginning of embryonic development. Thus, the vertebrae do not close around the developing spinal cord; some of the spinal cord may push or protrude through, causing nerve damage and other health issues. An estimated 1 in 2,500 infants worldwide have spina bifida.

Overall, there are four main forms of spina bifida. First is spina bifida occulta, the most mild and common form. In this form, the vertebrae are malformed but the spinal cord and nerves develop normally. Because of this, the nerves do not protrude from the spine. Rather, they are covered by skin. In general, spina bifida occulta does not cause many health issues outside of back pain or impaired bladder function.

Next, closed neural tube defects are a group of defects in which issues with the fat, bone, or meninges (membranes that line the skull / the protective spinal cord covering) impact spinal cord development. Once again, these defects cause few health problems outside of bowel dysfunction and incomplete paralysis. After this comes meningocele, where the meninges and spinal fluid poke out from a spinal opening. In patients with meningocele, they still have normal spinal cord development. However, the protruding sac may cause bowel dysfunction and complete paralysis.

Finally, the most severe form of spina bifida is called myelomeninocele. In this form, both the spinal cord and meninges protrude from a spinal opening. In this form, most patients have partial or complete paralysis below the spinal opening, and may be unable to walk. Additionally, bowel dysfunction is present. Other symptoms of spina bifida outside of those mentioned include:

  • Seizures
  • Intellectual or developmental delays
  • Hydrocephalus (too much cerebrospinal fluid in the brain)

Learn more about spina bifida.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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