LAUSR

A 17-year-old boy was assessed because of a 1-week history of thoracic pain without dyspnoea. The patient came from Pakistan 2 years earlier. He had a history of asthma and had delayed puberty. The family described growth retardation since he began coughing a few years earlier. He presented with a current bone age and insulin-like growth factor-1 levels similar to those of a 13to 14-year-old boy with normal testosterone levels. He had no fever, systemic symptoms or lymphadenopathy and no history of trauma. No alterations were observed on physical examination. Chest radiography revealed a left upper lobe mass (Fig. 1A). Before these findings, an analysis with an immunological study and tumour markers, as well as a study of mycobacteria in sputum were requested, and these showed no abnormalities. Chest tomography showed a mass with poorly defined edges with a mucus plug in the left bronchus and bronchiectasis (Fig. 1B). A sweat test was positive (91 mEq/ L), and subsequently confirmed (86 mEq/L), therefore cystic fibrosis (CF) was diagnosed. Three weeks later, the lung mass had disappeared on chest X-ray. The patient had neither a known family history of CF nor did he present clinical or laboratory abnormalities suggestive of malabsorption, pancreatic involvement, hepatobiliary or musculoskeletal disease, and there were no alterations in the vas deferens. Spirometry showed a non-obstructive pattern (forced expiratory volume during the first second (FEV1) of 59%, forced vital capacity of 74%) with a positive bronchodilator test (FEV1 of 67%) and sputum cultures were negative. CF transmembrane conductance regulator genes (CFTR) sequencing was requested, analysing exons and flanking intronic areas of the CFTR gene and showing a variant of the pathological CFTR gene in heterozygosis, 5T(TG12) in IVS8, and uncertain significance variant, c.322T>C, that implied a change of serine to proline at position 108 (S108P). The patient had no family history of CF; and the family was unaware of neonatal screening. The parents lived in Pakistan and no genetic study had been conducted. This patient was diagnosed with CF based on clinical (bronchiectasis) and laboratory criteria (two positive sweat tests). CF is an autosomal recessive disease caused by pathogenic variants in the CFTR gene on chromosome 7q31. Three alleles have been identified in IVS8; 9T, 7T and 5T with 5T associated with incomplete penetrance. There are 176 patients with 5T(TG12) variant in the CFTR2 database, some diagnosed with CF when combined with another CF-causing variant, triggering pancreatic insufficiency in 14% and FEV1 between 39 114%. It is a variant with variable clinical consequences that is very frequent in the population from newborn screening and it is reported to be associated with a tendency of the sweat test to increase to pathological values over time. In contrast, the S108P variant has not been described for CF in consulted databases (CFTR1, CFTR2 database and ClinVar). Seydewitz et al. described a similar case of a patient with bronchiectasis and pathological sweat test and mild pulmonary disease with the S108F variant, which implies a change from serine to phenylalanine at position 108 in exon 8. In conclusion, although a c.322T>T variant has uncertain meaning, its description in a patient with