Examination of Cases Who Had Molecular Testing with the Presumptive Diagnosis of Cystic Fibrosis: Experience of a Single Center

Abstract

Objective: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene, leading to multisystem involvement. Early diagnosis is crucial for managing complications and improving patient prognosis. This study aimed to evaluate the clinical and demographic characteristics and molecular analysis results of patients who underwent CFTR gene mutation analysis with a preliminary diagnosis of CF. Materials and Methods: A total of 34 patients were included in the study. Clinical and demographic data, along with genetic analysis results, were retrospectively examined. The frequency of symptoms associated with CF was determined, and the relationship between genetic findings and clinical manifestations was analyzed. Results: The most common reason for admission was respiratory symptoms, accounting for 64.7% of cases, followed by gastrointestinal complaints and malnutrition. Malnutrition was found to be significantly associated with a positive CFTR gene mutation (p=0.027). The risk of detecting a CFTR gene mutation was 5.667 times higher in patients with malnutrition. Conclusions: This study highlights the necessity of considering CF in the differential diagnosis of children presenting with recurrent respiratory tract infections and malnutrition, even in the absence of a positive family history. While respiratory symptoms were the most common reason for admission, malnutrition was found to be significantly more prevalent among mutation-positive cases. These findings underscore the importance of supporting careful clinical evaluation with genetic analysis in the diagnostic process of CF. Further large-scale, multicenter studies are needed to confirm and expand upon these results.

Keywords

• CFTR gene
• cystic fibrosis
• heterozygous mutation
• malnutrition
• recurrent lower respiratory tract infection

Kistik Fibrozis Öntanısıyla Moleküler Test Yapılan Olguların İncelenmesi: Tek Merkez Deneyimi

Öz

Giriş: Kistik fibrozis (KF), Cistic fibrosis Cystic Fibrosis Transmembrane Regulator (CFTR) genindeki mutasyonlar sonucu ortaya çıkan otozomal resesif geçişli bir hastalıktır ve multisistemik tutulum gösterir. Erken tanı, komplikasyonların yönetimi ve hasta prognozu açısından kritik öneme sahiptir. Bu çalışmada, KF ön tanısı ile CFTR gen mutasyon analizi yapılan hastaların klinik ve demografik özellikleri ile moleküler analiz sonuçlarının değerlendirilmesi amaçlandı. Materyal ve Metot: Çalışmaya toplam 34 hasta dahil edilmiştir. Klinik, demografik veriler ve genetik analiz sonuçları retrospektif olarak incelenmiştir. KF ile ilişkili semptomların sıklığı belirlenmiş ve genetik bulgular ile klinik belirtiler arasındaki ilişki analiz edilmiştir. Bulgular: Başvuru nedenleri arasında en yaygın olanı %64,7 oranıyla solunum yolu semptomlarıydı; bunu gastrointestinal şikayetler ve malnütrisyon izledi. Malnütrisyon, CFTR gen mutasyonu pozitifliği ile anlamlı şekilde ilişkili bulundu (p=0,027). Malnütrisyonu olan hastalarda CFTR gen mutasyonu saptanma riski 5,667 kat daha yüksekti. Sonuç: Bu çalışma, tekrarlayan solunum yolu enfeksiyonları ve malnütrisyon ile başvuran çocuklarda, aile öyküsü olmasa dahi, ayırıcı tanıda kistik fibrozisin mutlaka göz önünde bulundurulması gerektiğini vurgulamaktadır. Solunum semptomları en sık başvuru nedeni olmakla birlikte, malnütrisyonun mutasyon pozitif olgularda anlamlı derecede daha sık görüldüğü saptanmıştır. Bu bulgular, kistik fibrozis tanı sürecinde dikkatli klinik değerlendirmenin genetik analizle desteklenmesinin önemini ortaya koymaktadır. Bulguların doğrulanması ve genişletilmesi için daha geniş çaplı, çok merkezli çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

• Kistik Fibrozis
• CFTR geni
• Heterozigot mutasyon
• Malnutrisyon
• Tekrarlayan alt solunum yolu enfeksiyonu

References

1. Graeber SY, Mall MA. The future of cystic fibrosis treatment: From disease mechanisms to novel therapeutic approaches. Lancet. 2023;402(10408):1185-1198.
2. Ong T, Ramsey BW. Cystic fibrosis: A review. JAMA. 2023;329(21):1859-1871.
3. Chen Q, Shen Y, Zheng J. A review of cystic fibrosis: Basic and clinical aspects. Animal Model Exp Med. 2021;4(3):220-232.
4. De Boeck K. Cystic fibrosis in the year 2020: A disease with a new face. Acta Paediatr. 2020;109(5):893-899.
5. Bierlaagh MC, Muilwijk D, Beekman JM, van der Ent CK. A new era for people with cystic fibrosis. Eur J Pediatr. 2021;180(9):2731-2739.
6. Farrell PM. Why cystic fibrosis newborn screening programs have failed to meet original expectations… Thus far. Mol Genet Metab. 2023;40(1-2):107679. doi:10.1016/j.ymgme.2023.107679
7. Weber SA, Ferrari GF. Incidence and evolution of nasal polyps in children and adolescents with cystic fibrosis. Braz J Otorhinolaryngol. 2008;74(1):16-20. 
8. Yavas C, Dogan M, Ozgor B, Akbulut E, Eroz R. Novel biallelic nonsense mutation in IGHMBP2 gene linked to neuropathy (CMT2S): A comprehensive clinical, genetic and bioinformatic analysis of a Turkish patient with literature review. Brain Dev. 2025;47(1):104313. doi:10.1016/j.braindev.2024.104313

9. Yavas C, Arvas YE, Dogan M, et al. Revealing Molecular Diagnosis With Whole Exome Sequencing in Patients With Inherited Retinal Disorders. Clin Genet. 2025;108(1):14-21. 
10. Cakmak Genc G, Yilmaz B, Karakas Celik S, Aydemir C, Eroz R, Dursun A. Radiosensitivity in a newborn with microcephalia: A case report of Nijmegen breakage syndrome. Birth Defects Res. 2024;116(5):e2346. doi:10.1002/bdr2.2346
11. Manjunath S, Mahajan R, De D, et al. The severity of malnutrition in children with epidermolysis bullosa correlates with disease severity. Sci Rep. 2021;11(1):16827. doi:10.1038/s41598-021-96354-z
12. Priel E, Adatia A, Kjarsgaard M, Nair P. CFTR heterozygosity in severe asthma with recurrent airway infections: A retrospective review. Allergy Asthma Clin Immunol. 2022;18(1):46. doi:10.1186/s13223-022-00684-0.
13. Polgreen PM, Comellas AP. Clinical Phenotypes of Cystic Fibrosis Carriers. Annu Rev Med. 2022;73:563-574.
14. McDonald CM, Reid EK, Pohl JF, et al. Cystic fibrosis and fat malabsorption: Pathophysiology of the cystic fibrosis gastrointestinal tract and the impact of highly effective CFTR modulator therapy. Nutr Clin Pract. 2024;39(1):57-77.
15. Culhane S, George C, Pearo B, Spoede E. Malnutrition in cystic fibrosis: A review. Nutr Clin Pract. 2013;28(6):676-683.
16. Schlüter DK, Griffiths R, Adam A, et al. Impact of cystic fibrosis on birthweight: A population based study of children in Denmark and Wales. Thorax. 2019;74(5):447-454. 
17. Nick JA, Chacon CS, Brayshaw SJ, et al. Effects of gender and age at diagnosis on disease progression in long-term survivors of cystic fibrosis. Am J Respir Crit Care Med. 2010;182(5):614-626. 
18. Bozkanat KM, Jain R. Sex differences in cystic fibrosis across the lifespan. In: Sex-Based Differences in Lung Physiology. United States, US: Springer Cham;2021:145-168.
19. Steffen LM, Pezzin LS, Sulis N, Steffen N, Pinto LA. Upper airway findings and markers of lung disease progression in patients with cystic fibrosis. Int Arch Otorhinolaryngol. 2020;24(4):e434-437.
20. Mantoo MR, Kabra M, Kabra SK. Cystic fibrosis presenting as pseudo-bartter syndrome: An important diagnosis that is missed! Indian J Pediatr. 2020;87(9):726-732.
21. Steinraths M, Vallance HD, Davidson AGF. Delays in diagnosing cystic fibrosis: Can we find ways to diagnose it earlier? Can Fam Physician. 2008;54(6):877-883.