Okay, this is really cool.  I am a graduate student in cell and molecular
biology.  I just now did a MedLine search on Waardenburg Syndrome and found
out some very interesting (to me) things.
 
Some researchers have found a gene that when defective can cause a certain
type of Waardenburg Syndrome.  (There are apparently different types.)  This
gene is called Pax-3.  The interesting thing about this is that Pax-3 is a
homeobox gene (fairly closely related to the genes I am working on in the
lab).  I will try to make this understandable so please bear with me if you
are interested....
 
Homeobox genes code for homeobox proteins which are generally genes that
are active during development of an organism.  They act as transcription
factors, which means that they are responsible for 'turning on' other
genes.  For example a transcription factor protein binds to the ''control''
region of another gene and allows that gene to be turned off or on.  This
regulates whether or not that gene will be transcribed and translated to
make a protein.
 
As this suggests, there are often very convoluted pathways in gene
regulation, in which several (even 10s to 100s) of gene products (proteins)
are involved in a particular pathway.  For this reason there are probably
many genes that can contribute to Waardenburg Syndrome.  If any gene in
this pathway is mutated then there's the possibility of a phenotypical
manifestation.
 
Several genes have been implicated in Waardenburg Syndrome.  Pax-3,
Sox-10, and MITF.  Some researchers think that these are all in the
same pathway.  What these genes seem to do (normally) is affect the
development and distribution of neural crest cells.  These are cells
that, during development, migrate from the developing neural plate, to
different portions of the fetus and contribute to a whole host of
structures generally associated with vertebrates.  (i.e., as far as I
know invertebrates don't have neural crest cells).  The formation of ear
structures are one of the things that neural crest cells contribute to.
Neural crest cells also contribute to the migration of pigment cells, which
explains the funny pattern of blaze ferrets!  The migration of these cells
is disrupted along the midline of the fetus and therefore you get a streak
with no pigment along the head.
 
Some people on this list have stated that the genes for the coloration
patterns and the genes for deafness are closely linked.  From what I read
I don't think that's really the case.  I think it's the same gene that
contributes to both the deafness and the coloration patterns.  The fact
that it is a gene that is active during development explains the wide
effect it has on the organism.  This is probably the reason that there are
some blaze ferrets that are NOT deaf as there are different variations of
the disease in which different genes in the pathway are affected.  Some
genetic mutations probably result in deafness and some probably do not.
(That's a hypothesis not a statement of fact!).
 
Waardenburg Syndrome does seem to be related to other health problems such
as intestinal problems, other sensory problems and some neural problems,
but I didn't read much about those.  I may do so later, or if anyone is
interested they can do a Medline Search at this web address:
 
http://www.ncbi.nlm.nih.gov/PubMed/
 
For anyone who is interested, the gene I am currently working on is Crx,
which is a homeobox gene that is expressed only in the developing and adult
eye.  It also seems, as most homeobox genes do, to be very important in
pattern formation.  Mutations in the Crx gene can result in congenital
vision diseases.  Crx and Pax genes are very similar as far as amino acid
composition goes.
 
Anyone is welcome to email me if they didn't understand what I wrote, and
I will try to make it clearer!
 
Leigh W.
[Posted in FML issue 3121]