Mutation V470M homozygous

Question

Dear expert team,

My 5-month-old niece was diagnosed with the V470M homozygous mutation.

Polymorphism:
In3: c.274-179G>A (rs1429566)- homozygous
In9: c.1210-13G>T (RS10229820)- heterozygous

I have not been able to find any hits on the internet; I assume it is a rare mutation, since our treating professor in Turkey could not give us any more detailed information on this mutation.

Our little one weighs 4890g, her pancreatic elastase value is >500 µg/g, she is currently not taking pancreatin. She inhales salbutamol 2.5mg 4x1/2 and budesonide 0.5mg/ml 2x1 daily. I would be grateful for any information/literature concerning this mutation.

Regards.

Answer

Hello,

The mutation you call V470M is usually referred to as M470V. It is a relatively common polymorphism without clinical consequences (according to the European “Best Practise Guidelines,” Dequeker et al. 2009, European Journal of Human Genetics, 17; pp. 51-65). Homozygosity for M470V would not explain CF. According to several scientific publications, M470V could at the most have a certain modifying influence on the CFTR function, i.e. in interaction with other mutations of the CFTR gene, it could influence their effect. To avoid misinterpretations, the guidelines on the molecular genetic diagnostics of CF recommend either not communicating these kinds of polymorphisms at all, or clearly marking them as polymorphisms without clinical consequences.

In summary, none of the genetic variation you mention can explain CF. Should your niece really be affected by CF, it would have to be caused by homozygosity for another mutation or by compound homozygosity for two other mutations.

Kind regards
Prof. M. Stuhrmann-Spangenberg

30.08.2011

30.08.11
Here some further thoughts on the case beyond the genetic point of view:
The question here is, why a mutation analysis of the CFTR gene has been performed: cases of CF in the family? Or clinical symptoms of the baby? In case the baby showed clinical symptoms: which kind of symptoms? As the baby is already inhaling, one would think of symptoms of the airways, however the inhalation of budenosid fits more to asthma than to CF. And if those symptoms were suspicious for CF, the gold-standard for diagnosis and the first investigation would be a sweat test in a certified CF center with pilocarpine ionotophoresis. The genetic investigation, measurments of the pancreatic elastase in the stool, measurements of the potential differences are further tests to confirm or clarify the situation if necessary. But the first line test for diagnosis of CF remains the (repeated) sweat test.
D. d'Alquen