388 Detection of a novel CFTR mutation c.122C>G (p.Pro41Arg) in a young cystic fibrosis (CF) patient with recurrent respiratory symptoms

Background: At present more than 1800 mutations have been described in the CFTR-gene. Several rare mutations are believed to cause mild lung disease and late onset of symptoms. We present a 5 y old Belgian boy heterozygous for an atypical CFTR variant and a novel variant which was never described before. Case report: A 5 y old boy with recurrent bronchitis and chronic sinusitis was referred to our clinic with repeated abnormal sweat chloride (Cl) (right 70mEq/L; left 53mEq/L) and elevated sweat sodium values (right 86mEq/L; left 62mEq/L), performed by Gibson and Cooke gauze method. Chest CT scan showed bronchial wall thickening and mucous plugging, without bronchiectasis. He is pancreatic sufficient, without history of pancreatitis. By screening the coding region of CFTR, using sequencing and MLPA (Multiplex Ligation-dependent Probe Amplification), he was shown to be heterozygous for c.224G>A (p.Arg75Gln − legacy name: R75Q) and c.122C>G (p.Pro41Arg), a novel variant which was never described before. Analysis of the parents is ongoing to prove that both variants are on different alleles. Discussion: R75Q is described as a variant overrepresented in patients with atypical CF, sarcoidosis, COPD and chronic pancreatitis and rather influences bicarbonate conductance than Cl. Our young patient has already respiratory symptoms and abnormal sweat chloride values. To our knowledge CFTR p.Pro41Arg has never been described before and its clinical relevance is not clear. As this boy has signs and symptoms of CF disease in combination with an atypical CFTR mutation, this novel mutation might be involved. However, mutations outside the coding region cannot be excluded.