Here are thoughts on the 5T allele,

The 5T allele has had a lot of press recently (and
rightly so) and it’s important to know what all the
fuss is about. There are two quite distinct features
of the 5T allele.

Firstly, it can have a role as a mutation modifier.
Going back to R117H, this mutation can be on the same
chromosome as a 5T allele or a 7T allele. When R117H
is associated with 5T, it behaves more or less like a
cystic fibrosis mutation (although generally a milder
one). But when R117H is associated with a 7T allele,
it is much less harmful. Not completely benign, but
generally speaking, you would rather have the 7T
version. The trouble is, it has lousy ‘predictive
value’, because the two groups overlap in severity.
[It must be understood that we are talking about the
scenario where there is a typical cystic fibrosis
mutation such as DeltaF508 on one chromosome, and the
R117H (with either 5T or 7T) on the other.
Secondly, it can have a role as a partially-penetrant
mutation. Sorry about the terminology; it means that
sometimes it behaves like a mutation and sometimes it
doesn’t! In this case, we are talking about a 5T
allele being on the opposite chromosome to DeltaF508
(or other typical cystic fibrosis mutation). In other
words, you have DeltaF508 on one of your chromosome 7s
and a 5T allele on the other. Now, DeltaF508 has
wrecked one of your CFTR genes completely, but what of
the other one? If the 5T allele has not had too much
of an effect, you might be OK, but remember that it
does interfere with splicing. The bottom line is that
the DeltaF508/5T genotype is associated with a number
of presentations - it is seen in CBAVD, bronchiectasis
and so on (but not ‘classic’ Cystic Fibrosis). Again,
it’s a lousy predictor; if you picked up (by
screening, for instance) an individual with DeltaF508
and 5T, you would not really be able to say how that
person would present clinically.

A final note on the 5T allele. There has been some
fuss recently (in the US) about women being offered
prenatal diagnosis for the 5T allele. For example, one
parent has DeltaF508 and the other has 5T and they are
therefore at risk of having a child who is
DeltaF508/5T. Or alternatively, both parent have been
found to carry 5T and are at risk of having a child
who is 5T/5T. Prenatal diagnoses and even terminations
have been offered on the basis of finding 5T alleles
(and the lawyers are queuing up, I suspect!).

I suspect this has arisen from inappropriate use of a
test in which the manufacturer describes the 5T as a
mutation and inexperienced users of the kit have
interpreted this as being as severe or significant as
DeltaF508, for example. This is certainly a difficult
area and one in which there is still much to be
discovered.

I hope this helps,

Terry

--- runthefox65 <runthefox65@...> wrote:
> Hi, I am replying because my fiancee and i were
> kinda thrown into
> the same deal. I am curious to know what your
> symptoms are.
> Normally if one has the 5T allele mutation it is
> directly linked to
> pancreatic insuffiency. My fiancee has no known
> history in his
> family of cf but he has mutation of the delta F508
> at the 5T
> allele. He has no lung disease and infertility is
> out too since we
> have a daughter. His case is rare and we are doing
> most of the
> research ourselves. Maybe we can compare notes?
> Anyway good luck
> and best wishes that your husband is mutation free!\
>
> tiffany
> --- In cysticfibrosissupport@yahoogroups.com, "ask
> me nicely"
> <hl_n_poole@h...> wrote:
> > Hello,
> >
> > I was just tested for CF gene. I came back
> Negative for CF gene
> but
> > positive for a mutation. Something about the 5th
> allele. They
> are
> > now testing my hubby. They have stopped our
> infertility treatment
> > because of this. My questions are if i have a
> mutation and if dh
> > comes back pos. for CF could we pass to a child?
> And what if he
> is
> > also neg. but pos. for a mutation could we pass to
> a child. I
> guess
> > basically my question is what does it take to pass
> to a child?
> > thanks in advance,
> > Nicole
>
>


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