Still, extensive screening of the gene coding regions may be negative, as was the case in our patient. transport by amiloride (46.2 and 48.3?mV) but a normal chloride transport. The search for epithelial sodium channel (ENaC) gene mutations was negative. Finally, based on recent publications, we looked for the deep intronic mutation c.870-1110_1113delGAAT mutation: its presence in the patient, in compound heterozygosity with c.1521_1523del, p.Phe508del, confirmed the atypical CF disease. Treatment The patient was treated by oral itraconazole and 2?mg/kg/day oral steroids for 2?months followed by a 6-month decrease. As she was still presenting an active ABPA after this treatment, omalizumab was started. Outcome and follow-up Omalizumab allowed the resolution of the cough after 1?month, as well as the negativation of in the sputum and the negativation of the serology. After a 1-year treatment, the thoracic HRCT scan showed bilateral large cystic bronchiectasis in place of the alveolar consolidations and an improvement K02288 of the other diffuse bronchiectasis (figure 1). Two years after omalizumab was stopped, the patient was still free of ABPA. She had still no pancreatic and liver diseases, and her respiratory function tests and blood gases were normal (table 1). During all the follow-up, she pursued a normal scholar course and several sports. Discussion ABPA is a complex clinical entity that results from an allergic immune response to most often occurring in patients with asthma or CF. Primary diagnosis criteria include asthma, radiological evidence of pulmonary infiltration, positive skin test to serology, elevated total K02288 and/or testing, even if the CF neonatal screening was negative. Sweat chloride tests have to be performed in first intention, although some rare CF mutations are associated with normal or intermediate sweat chloride values.5 More Sh3pxd2a than 1900 gene sequence variations have been reported so far in patients with CF- and CFTR-related disorders (www.genet.sickkids.on.ca/cftr/app). As in our case, the 30 most frequent CF mutations are first tested and an extensive analysis should be further discussed depending on the clinical evaluation. Still, extensive screening of the gene coding regions may be negative, as was the case in our patient. In such situations, search for splicing defects in deep intronic regions, possibly by studying messenger RNA (mRNA) obtained from nasal epithelial cells, should be considered, as recently evidenced.6 7 In our patient, the recently described intron 7 c. 870-1113_1110delGAAT mutation was specifically screened for and identified, which led to confirm the diagnosis of atypical CF. This deletion of 4 base pairs (bp) was shown to be associated with an insertion of a new exon of 97bp in the mRNA between exons 7 and 8, which contains a premature stop codon. It was first described in three Italian patients having classical CF. A French collaborative study in patients suspected to have CF and who had no or only one known CF mutation led to identify 17 patients presenting CF or a CFTR-related disorder.6 Fourteen of them were originated from France or Italy, and geographic origin was K02288 unknown for the others. Among the 17 patients, four had a normal or intermediate sweat test and none of them presented an ABPA. The severity of the disease was extremely variable, from a severe, typical CF with pancreatic insufficiency and colonisation, to asymptomatic presentations. The fertility was also reported to be variable. Our young patient showed a mild lung CF disease with diffuse bronchiectasis and preserved lung function, chronic rhinitis, pancreatic sufficiency. Her fertility status is not known yet. Learning points The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in children must encourage physicians to search for cystic fibrosis (CF). Extensive analysis of the CF transmembrane regulator ( em CFTR /em ) gene, including search for rare intronic splicing mutations has to be performed before excluding a CF diagnosis. Omalizumab could be considered as an alternative therapy for cortico-resistant ABPA in CF children. Acknowledgments The authors thank Dr Corinne Troadec for referring the patient to Trousseau Hospital and to initiate the patient’s medical care in Centre Mdical Spcialis de l’Enfant et de l’Adolescent, Paris. The authors thank Dr Laurence Jonard for the CF30 sequence in Trousseau Hospital, and for referring the DNA to Dr Girodon. They also want to thank Alix de Becdelivre for DNA analysis with Dr Girodon. The authors thank Pr Isabelle Sermet for nasal potential difference testing in Necker Enfants Malades Hospital, and the authors thank Dr Thierry Bienvenu for the ENaC sequence in Groupe hospitalier Cochin-Broca-H?tel.