Nasal Potential Difference in suspected CF patients with 5T polymorphism * Comparison between patients from Israel and Netherlands

For different CFTR mutations is is known that they can ause CF. However for
some mutations in the CFTR gene it is not certain if they cause CF or in
combination with which mutations they might. 5T polymorphisme is one of those
mutations. Persons who are homozygous for this mutation, or persons who have
this mutation on one allele and have no CF causing mutation on the other, have
an increased chance of CBAVD (congenital bilateral absence of vas deferens).
Hyterozygocy for 5T polymophism combined with a known CF-causing mutation is
associated with CF with atypical presentation. In Ashkenazi Jews this mutation
is present in 18% of CF patients with atypical presentation, in not-Ashkenazi
Jews this is 10%. In CBAVD in Askenazi Jews, 32% of cases is due to 5T
polymorphism and in non-Askenazim this is 36%. This mutation is also present in
other ethnic groups. Is is not know to what extent this mutation in itself or
in combination with another mutation leads to a reduction in CFTR function, and
to what extent this leads to health complaints. Through this study we want to
clarify this. Possibly CFTR function is dependent on the mutation that is
present on the other CFTR allele. Those mutations probably differ between the
Dutch and Israeli population, which is why we want to compare Israeli patients
(data already available) with Dutch patients.

Clarify the effect of 5T polymorphism with or without another CF causing
mutation on the other allele, on the CFTR function.

An NPD test is performed in about 30 persons with a 5T polymophism. The average
values of the test are calculated for the group of 5T homozygotes and for de
group of persons with one 5T in combination with another CF causing mutation.
These values are compared with the referece values for NPD. Through an ANOVA
test the significance of the difference between the outcomes of the groups is
assessed.
Additionally the 95% CI is calculated per group and overlap in the values is
evaluated.
The same is done or de patients in Israel, and the Dutch patient groups will be
compared to de Israeli patient groups.

The burden and risk of perticipation are minimal.

The patient needs to sit still throughout the measurement in a neutral
position.
The salt solutions and subcutaneous needle used, are safe. Some iiritation or
bleeding of the nasal mucosa may occur.