Medullary Kidney Disease
Medullary Kidney Disease 1 Genetics
What causes Medullary
Kidney Disease Type I?
Medullary Kidney Disease Type I (MKD1) is caused by a mutation (change) in a
gene. In this case, it is a mutation in
a gene called MUC1
that makes a protein called Mucin-1.
What is a gene and a
Genes store the information for
making everything in our body: kidneys, blood, how to process the foods we eat,
etc... Genes are messages that are used to
make proteins. Sometimes a little
mistake can be made in the message, like a typo. This little mistake causes the protein to be
made in the wrong way. The abnormal
protein will not work properly and cause problems in the body.
For example, imagine that genes
are the blueprints for a factory. If
there is a mistake in the blueprint, the factory will have a problem. Sometimes the problem is minor, and no one
may know the problem exists. Other times, the problem is major, and the factory
is unable to make its products or make them correctly.
Another way to look at it is to think of a gene as a sentence that
reads: THE CAT SAT. When a gene is
mutated, that sentence is changed.
Sometimes the sentence will still have meaning -
- If the “T” in CAT is swapped
with an R: THE CAR SAT.
Other times, the change makes the sentence meaningless
- If the “T” in CAT is deleted: THE CAS AT.
- If a “B” is inserted before CAT: THE BCA TSA T.
If a mutation makes a gene’s
message meaningless, the protein it makes will not be able to work properly.
MKD1 is caused by an insertion into the MUC1 gene.
What does the mutation in MUC1 do?
The mistake in the MUC1 gene causes slow worsening of
kidney function but no other problems.
What mutation causes MKD1?
Doctors working at the Broad
Institute in Boston, Massachusetts found that a mutation in the gene called MUC1 causes MKD1. All families that have been studied have the
same MUC1 mutation.
MUC1 makes a protein called Mucin-1, or Mucoprotein-1 (18
mucins have been found so far).
Mucin-1 helps make mucus, a physical barrier to protect our
bodies. Mucin-1 is found all over the body, especially in the lung, breast,
skin, stomach, salivary glands and kidney.
How does a mutation in MUC1 cause
kidney damage in MKD1?
In MKD1, the abnormal Mucin-1 is not able to perform its job, and cannot be used in the cell. The abnormal protein builds up in the kidney
cells. How it causes kidney failure is
still being determined.
Is Mucin-1 made only in the kidney?
Mucin-1 is made in many tissues, but
for some reason it only causes kidney failure.
We do not know why this is.
How is MKD1 inherited?
We all have two copies of the MUC1 gene, one from our father and one
from our mother.
For patients with MKD1, one of
the copies has a mutation, and even though they have a good copy as well, it
cannot make up for the buildup of the abnormal Mucin-1.
A person with MKD1 has one good
copy and one mutated copy. When a
patient with MKD1 has a baby, they either passes on the good copy to the child
(who will not have MKD1) or the mutated copy (who will have MKD1). It is entirely by chance
if the good copy or the mutated copy is given to the child.
There are a lot of unanswered questions about
MUC1 and MKD1, such as:
- What controls the
MUC1 gene? If we can figure out what
makes the gene work, it will help us know what to do to treat the
disease. We are now studying how the gene works in the
- How and why does the abnormal Mucin-1 build up
in the cells? Abnormal Mucin-1 accumulates in
the kidney cells.
- How does this accumulation lead to MKD1? We are
growing cells in the laboratory that make the abnormal protein, and
we are studying what it does to them.
- Why do problems only occur in the kidney when the
abnormal Mucin-1 is made in many cells in the
body? To study this, we are looking at
biopsies that have been done of other tissues in patients with this
disease. We know that the abnormal protein is present in
these tissue biopsies, but it does not seem to make cells of other
organs besides the kidney die.
- Why do some patients have mild disease and others
have severe disease? We have noticed
by studying many different families that in some the disease is
relatively mild, whereas in other families the kidney disease
starts early in life. We are trying to figure out why there
is such a difference. If we can understand this, it would
help us identify potential treatments.
Researching the MUC1 gene, Mucin-1, and MKD1
in patients is the only way forward to finding ways to help treat
and slow the progression of the disease.
We are also excited to be working with the Uromodulin Kidney Disease
Foundation which provides support for families, doctors and
researchers. For more information, visit: ukdcure.org
This webpage provides only general information. Please consult your physician for recommendations specific to your care. If you think you may have this disease or another type of inherited kidney disease that no one can tell you the cause, please contact Dr.Anthony Bleyer at firstname.lastname@example.org
or call 336-716-4513.