| MadSci Network: Molecular Biology |
Let me answer your question in two parts: first I'll talk about mutations in general, and then about von Willebrand disease.
Mutations occur in the DNA, and alter the meaning of a gene that encodes another molecule, usually a protein. A mutation occurs when one of the bases, or "letters", is changed to another one by a mistake in replication or damage caused by external influences. This change alters the meaning of the code for that gene. The mutation is passed on from parent to child in the case of genetic diseases, such as von Willebrand disease. When the gene is transcribed into mRNA, the mistake is copied right along with the rest of the gene. Then, when the mRNA is translated into protein, the mistake is now present in the protein. Often, the mistake in the protein consists of a wrong amino acid being incorporated into a protein at a given position (missense mutation; a protein is a long chain of amino acids, and the properties of the protein are determined by the order of the amino acids). Sometimes a protein is prematurely stopped (nonsense mutation). Both types of mutation are found in von Willebrand disease.
An analogy of the process by which DNA makes protein is as follows: the DNA is a series of large manuals that are locked in a room (the nucleus) in a house (the cell). These manuals contain the blueprints needed to make all the parts (protein) of the house. In order for the workers to get the blueprints they are first copied by a clerk (this is transcription) and the copy (mRNA) is passed out of the locked room. When the house divides (this is where the analogy breaks down!) the manuals are themselves copied, so that each new house has a copy. Now it may be easier to see how a mistake in the manual will be copied, and then mislead the workers into making faulty parts.
Now a short word about von Willebrand disease. In general three types are recognised. Type I is the result of lowered amounts of the vW factor, and resultant reduced factor VIII. Type II is the result of mutations such as the ones discussed above. The mutations you mention, which occur in the factor VIII binding domain of vW factor, are responsible for type 2N von Willebrand disease. Type 2 vW disease is variable in its clinical manifestation. Finally type 3 is characterised by an almost complete absence of vW factor.
(I'm not sure why you asked this question - are you a student? If you require more detailed information about vW disease I'd like to refer you to the following reference:
J. Evan Sadler (1995) "von Willebrand Disease" Chapter 107, pp 3269-3287. in The Metabolic and Molecular Bases of Inherited Disease, Volume III. (7th Edition); McGraw Hill; Scriver, Beaudet, Sly and Valle, eds.
If you have trouble locating the article please let me know (obogler@ucsd.edu) and I'll get a copy for you.