Androlog Mail
It appears that I need to restate my questions:
First, is there any data on penetrance rates for CBAVD in double CF
mutation males with either two classic mutations or one classic and one
5T allele. I would think that someone would have looked at post
pubertal males in a CF clinic and generated some data on the number who
are azoospermic. It might be less likely that anyone has looked at a
general population to find men with one classic mutation and one 5T and
then looked for azoospermia. However, there may have been a
retrospective look at male relatives of men with CF/5T to see if
brothers with the same genotype had the same phenotype (maybe Silber or
Van Steirteghem have the data?). With more wide spread general
screening we will have a chance to look at this question. We will have
a number of men found to have a single classic mutation with 5% of those
also carrying 5T. Now on the one hand, most of these will be found on
prenatal screens and therefore be presumed fertile. On the other hand,
the investigator may discover more azoospermic 'fathers' than they care
to deal with, i.e. misassignment of paternity.
My case with oligospermia and 5T positive with negative CF mutation
analysis was presented only because the lab did the 5T study without it
being ordered specifically and not as a reflex study to any mutation
found. Obviously he does not have CBAVD and I do not think there is any
reason to suspect a relationship between the 5T allele and his
oligospermia. It brings up the question of potential obligation to
screen his wife. She has been screened and is negative for the classic
mutations. I did not order a 5T allele on her and do not plan to. As
an aside, Quest Diagnostic did not report any negative 5T screens on
standard CF screens only positive screens - I have no idea what was
going on in their lab and why they did the screens on the two patient
reported as 5T positive. Three cases of CBAVD have been brought to my
attention where the cause was homozgosity for 5T (5T/5T) with no other
mutations. I do not know if these men had other symptoms related to
lung or pancreas. If there was a risk of other substantial problems
then I would have to screen the wife. My assumption is that these
people do not have substantial other problems otherwise 5T allele
testing would have been added to the standard CF screen since it is the
most common CF mutation.
The CBAVD case has R334W/G551D 7T/7T. His wife was reported by Quest as
CF negative 5T positive (no more information given, i.e.: 5T/5T, 5T/7T?
don't know). Question of penetrance of CBAVD in males who are R334W/5T
and G551D/5T then arises. Also, is this an indication for newborn
assessment for genotype. What is the worse respiratory/pancreatic
phenotype we will see in the offspring? Unfortunately, this
physician/nurse couple will not go to the genetic counselor. He has
been advised to have further testing in regards to CF and cancel his
planed trip to the mountains of Peru. So far he has done none of this.
Mark Jutras, MD
Orlando, FL
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