Late-Diagnosed Cystic Fibrosis with Co-Occurring CFTR 3849+10kbC>T and 5T Variants: A Case Report.

Background

The deep-intronic variant 3849+10kbC>T preserves residual CFTR function and is recurrently associated with pancreatic sufficiency, normal or borderline sweat chloride and diagnosis beyond early childhood. A co-occurring poly-T 5T allele adds a second layer of uncertainty: its penetrance depends on the TG repeat carried in cis, and its contribution to the phenotype can be weighed only once its phase relative to the second variant has been established. Case Presentation: A boy with recurrent respiratory infections from the age of three was diagnosed with cystic fibrosis at 12 years, in 2018-four years before newborn screening became national policy in Romania. Two sweat conductivity measurements, 125 and 80 mmol/L NaCl-equivalent, together with targeted CFTR analysis identifying 3849+10kbC>T and a 5T allele, established the diagnosis. Phase was not determined-parental samples were not obtained and no allele-specific or long-range analysis was performed-so the two findings are reported as co-occurring rather than as demonstrably in trans. His elder brother, who had recurrent spontaneous pneumothorax and two negative sweat tests, was never genotyped because the test was not reimbursed. Bilateral bronchiectasis and chronic airway infection followed; inhaled colistimethate eradicated Pseudomonas aeruginosa, whereas Staphylococcus aureus persisted despite successive antibiogram-guided regimens. Access to elexacaftor/tezacaftor/ivacaftor was granted in January 2026 on the basis of the genotype.

Conclusions

Molecular characterisation contributed to a diagnosis that rested on the combination of clinical phenotype, abnormal sweat conductivity, and CFTR analysis, and was, eight years later, the sole criterion for access to modulator therapy; phase and TG-repeat length remain undetermined. No follow-up data are available, therapy having been authorised but not yet started at the time of writing.