Late-Diagnosed Cystic Fibrosis with Co-Occurring CFTR 3849+10kbC>T and 5T Variants: A Case Report
6 affiliations
- 1Grigore T. Popa University of Medicine and Pharmacy, 700115 Iaşi, Romania
- 2Department of Pediatrics, Saint Mary’s Emergency Children Hospital, 700309 Iași, Romania
- 3Regional Center for Medical Genetics Iasi, Saint Mary’s Emergency Children Hospital, 700309 Iași, Romania
- 4Department of Obstetrics and Gynecology, Cuza-Voda Clinical Hospital of Obstetrics and Gynecology, 700038 Iaşi, Romania
- 5Department of Surgery II—Pediatric Surgery, Saint Mary’s Emergency Children Hospital, 700309 Iași, Romania
- 6Regina Maria Healthcare Campus, 700023 Iaşi, Romania
Abstract
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.
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BibTeX
@article{popovici2026latediagnosed,
title = {{Late-Diagnosed Cystic Fibrosis with Co-Occurring CFTR 3849+10kbC>T and 5T Variants: A Case Report}},
author = {Paula Popovici and Adriana Mihai and Lăcrămioara Ionela Butnariu and Razvan Mihai Popovici and Alina Mariela Murgu and Elena Tarcă and Ileana Katerina Ioniuc and Tania Elena Rusu and Dana-Teodora Anton-Păduraru and Oana-Raluca Temneanu},
journal = {Journal of clinical medicine},
year = {2026},
month = sep,
doi = {10.3390/jcm15197584},
url = {https://europepmc.org/article/PMC/PMC13665875},
note = {CC BY},
}
RIS
TY - JOUR
TI - Late-Diagnosed Cystic Fibrosis with Co-Occurring CFTR 3849+10kbC>T and 5T Variants: A Case Report
AU - Paula Popovici
AU - Adriana Mihai
AU - Lăcrămioara Ionela Butnariu
AU - Razvan Mihai Popovici
AU - Alina Mariela Murgu
AU - Elena Tarcă
AU - Ileana Katerina Ioniuc
AU - Tania Elena Rusu
AU - Dana-Teodora Anton-Păduraru
AU - Oana-Raluca Temneanu
PY - 2026
DA - 2026/09/30
JO - Journal of clinical medicine
DO - 10.3390/jcm15197584
UR - https://europepmc.org/article/PMC/PMC13665875
AB - 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.
SN - 2077-0383
ER -