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 mutation?

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. 

 MUC1

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.

 Inheritence with chromosomes

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 laboratory.
  • 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 kidney@wakehealth.edu or call 336-716-4513.

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Last Updated: 04-07-2014
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Disclaimer: The information on this website is for general informational purposes only and SHOULD NOT be relied upon as a substitute for sound professional medical advice, evaluation or care from your physician or other qualified health care provider.