Negative gene sequencing and negative sweat test

Question

Can you rule out cystic fibrosis with a negative gene sequencing and a negative sweat test?
Is the sequencing reliable and able to rule out the disease in a child?
Thank you very much

Answer

Hello,
Confirmation of cystic fibrosis diagnosis is based on:
- a positive sweat test, say showing a sweat chloride content equal to or greater than 60 mmol / L;
- and/or the detection of two mutations in the cystic fibrosis gene (CFTR mutation).
These results are valuable only if they are carried out by authorized staff using appropriate equipment and techniques.

The first mission of the CF Center is precisely to confirm or rule out the diagnosis during a consultation including clinical examination and doing a sweat test:
- If the sweat test carried out in the conditions is clearly negative, sweat chloride less than 30 mmol/l, the diagnosis can be ruled out without a search of CF mutations;
- If the sweat test shows a result called "intermediate", say showing a sweat chloride between 30 and 60 mmol/L, a search for mutations in the CFTR gene is necessary to diagnose an atypical form of cystic fibrosis. This genetic testing should be performed by a reference laboratory capable of performing an extensive study of the CFTR gene by sequencing. If this study is negative, the likelihood of an atypical form of cystic fibrosis is negligible: it is however not completely zero because the possibility of unknown mutations located in a part of the gene not explored by sequencing remains theoretically possible.
Wishing that answers your question.
Best regards,

Gilles RAULT, MD, Roscoff CF Center

01.02.2016