Heterozygous mutation in the CFTR gene

Question

Hello,

In my son (4 years 11 months, developed according to age) a heterozygous misincorporation c.1408G>A (p.V470M) in exon 11 of the CFTR gene was identified.

The background:

Since a lobar pneumonia two years ago that was treated in the hospital, my son has been suffering from numerous infections. Until today, he has been diagnosed with a total of eight other lobar or atypical pneumonias. A sweat test carried out in the context of pulmonary diagnostics in April showed borderline values of 38mml/l and was therefore repeated. The second result, which we got just recently, was roughly the same (36mml/l).

A subsequent gene test returned the result mentioned above, though it was noted that the mutation detected was not the reason for the recurring pneumonias.

How would you evaluate this?

Kind regards.

Answer

Hello,

you are saying that your almost five-year-old son had lobar pneumonia two years ago and has since had eight further lobar or atypical pneumonias. In the context of a pulmonary exam, two sweat tests were carried out, both of which yielded borderline values (38 and 36mmol/l, respectively) for chloride. A subsequent molecular genetic exam showed a CF mutation (c.1408G>A (p.V470M)). You were told that that mutation was not the cause for the pneumonias. You are asking whether we would assess the result in the same way.

Overall, it has to be said that your son’s situation is typical of patients with borderline sweat tests. You are saying that he has been developing according to age so far. It can thus be assumed that the pancreas works normally. If this has not been checked for by a lab test (stool test for elastase I), you should definitely do so in order to confirm normal findings. Statistically, such a result would reduce the chance of an existing CF but not completely preclude that possibility. Theoretically, your son could have a second, very rare mutation that he has not been tested for so far in the molecular genetic exam. In order to get complete clarity for your son, it is necessary to do a nasal potential difference measurement or a rectal biopsy. [Translator’s note: information relating specifically to Germany was omitted in the translation.]

If these tests show that CF can be ruled out, you should look intensively for other possible causes of the unusual number of pneumonias. One could, for instance, think of a reflux disease with repeated aspirations, or of immunodeficiency. We wish you and your son all the best.

Kind regards,
Dr. H.-G. Posselt

14.02.2012