Rare Disease Spotlight - Kabuki Syndrome
If you're at all familiar with Japanese art or have been fortunate enough to visit Japan's theater scene, you're probably seen someone with Kabuki-style make up. This iconic style is characterized by dramatic, thick highlights around the eyes on top of a snow white background.
Figure 1: Some examples of Kabuki make up
In 1981, researchers from the Kanagawa Children's Medical Center in Yokohama, Japan identified a rare genetic disease that they subsequently reported on in The Journal of Pediatrics. They called the disease "Kabuki syndome", due to similarities between the appearance of the afflicted with the make up styles described above.
Figure 2: A child with Kabuki syndrome
Only 1 child in 32,000 births are diagnosed with Kabuki syndrome each year and they suffer from variety of congenital defects, ranging from hearing loss to growth deficiencies. The disease was only discovered about 30 years ago, so we lack any significant information regarding life expectancy, but there is no current indication that this disease shortens lifespan.
As with many rare disorders, the advent of robust gene sequencing techniques greatly assisted geneticists who were interested in Kabuki syndome's root biological causes. In 2010, Sarah Ng and colleagues reported that the disease was due to a mutation in a gene called MLL2. But what does this gene do? To fully explain, let's dive into a short biology lesson!
Imagine your cell. Small, healthy, and unassuming. Now, imagine a small speck in the center of that cell, about 10% of its total volume (this is normally around 6 micrometers, or six millionths of a meter). What you are now visualizing is the amount of space available for your cells to pack in all of the genetic information required to code for your entire body, which would be about two meters long if you stretched it end to end! How does your body cram all of that material into such a small space? From the perspective of the cell, it approaches this problem in the same way you would if you were packing clothes into a suitcase for a trip. The key is the way in which you pack everything!
As it turns out, DNA is wrapped very tightly around proteins called histones, which are then wound tightly around each other to form structures called chromosomes. Below is a nice illustration of how that all works:
Figure 3: Packing in the DNA!
Pretty incredible, right? As I mentioned earlier, Kabuki syndrome involves a mutation in a gene called MLL2. This gene codes for a type of enzyme called a methyltransferase, which is an enzyme that affects how tightly some of the DNA in your nucleus is wound up like in the picture above. This is important, as the DNA must be relaxed for it to be translated into proteins. When the DNA is wound up tight around histones and in chromosomes, your cells can't take a look at them because they're all covered up!
Thankfully, most of the medical issues associated with Kabuki syndrome can be helped with modern medicine. While we can't cure genetic disorders yet, science is also providing us with interesting solutions to these tough problems!