We all are made up of thousands of proteins. These proteins build structures like muscles and
organs, break down food to make energy, and move things around the body.
The instructions to make proteins are encoded in our genes. Each gene is the instruction manual to make one protein. We get these instructions from each of our parents, which means that, with some exceptions, we have 2 copies of the instruction manual to make each protein. This is a good thing, because it means that if there’s a typo in one instruction manual, we can just use the other.
Genes are organized into chromosomes. Think of a chromosome as a book and the genes as the pages in the book. Humans have 46 chromosomes – 23 of each type. Chromosomes are labelled one through twenty-two based on size (these numbered chromosomes are called autosomes) and then the twenty-third pair are the sex chromosomes, which determine biological sex. There are two sex chromosomes, an X-chromosome and a Y-chromosome. Girls have two X-chromosomes and boys have 1 X-chromosome and 1 Y-chromosome. This is the exception to the “two copy” rule we talked about before. Girls have two X chromosomes, whereas boys only have one. That means that for genes on the X-chromosome, boys do not have a second copy. So, if there is a typo in one of the genes there is no backup instruction manual.
A mutation is a change in a gene, a typo, that interferes with the gene’s ability to make a protein that works. Everyone has mutations. Most of the time the mutations do not cause any harm because there is a back up copy of each gene. As a side note, another term for “mutation” is “pathogenic variant” or “disease-causing variant”.
KIF4A is the name of the genes that gives the instructions to make the protein kinesin family member 4A. It lies on the X-chromosome, which means girls have two copies of the instruction manual to make KIF4A and boys have one.
We are all made up of boxes called cells. There are many different kinds of cells: cells that make up your skin, cells that make up your heart, cells that make up your muscle, and many more. Cells can be very large, so they have a system of cables to help move things around. These cables are called microtubules. They are a dynamic transport system that grows and remodels as the cells grow.
Kinesins are motors that help move things along microtubules. They have arms and legs: their arms grab and slide along the microtubules, and their legs grab different cargo within the cell and transport them along the microtubules.
Kinesin 4A is one type of kinesin. Like other kinesin, it is made up of three domains: a motor domain to power movement, a coiled-coil stalk domain, which allows for interaction with other proteins, and a globular domain, which helps in cargo binding and cargo docking.
We still have a lot to learn about the function of this kinesin. What we know is that it helps transport things in brain cells to get them where they need to be. We also think it may help cells divide by moving the chromosomes to the right place in preparation for cell division. We also think it may help repair damage that happens to our genes over time.
We are still learning what it means to have differences in how well KIF4A works. Right now, we think that people who have KIF4A that does not work well can have learning differences, developmental differences, seizures, and structural brain differences.
KIF4A pathogenic variants or mutations can be inherited. Mothers may carry a change in their KIF4A gene, but be unaffected, because they have another X-chromosome with another copy of the KIF4A gene to use as backup. They can pass the KIF4A gene change to their daughters, and their daughters can also carry the gene change and be unaffected. Importantly, mothers can pass the X-chromosome with the KIF4A gene change to their sons. Because the gene is on the X-chromosome, the son would have no backup copy and would have symptoms of KIF4A deficiency. KIF4A gene changes can also be new in the children.
Everyone in the world is a carrier of disease, usually multiple diseases. Most of the time, there is no way to know because disease carriers do not have symptoms and genetic testing is not widely done. Having a child with a KIF4A disease is no one’s fault. There was nothing anyone could have done to prevent it.