Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Aug;70(8):2684-2696.
doi: 10.1007/s10620-025-09094-9. Epub 2025 May 14.

Genetic Background of Eosinophilic Esophagitis and Esophageal Atresia in Children

Ipek Ulkersoy  1 , Ahsen Colakoglu  2 , Eymen Pinar  2 , Ece Kuduban  2 , Erkan Akkus  3 , Oguzhan Tin  3 , Nursena Kologlu Ates  3 , Khusan Khodzhaev  4 , Hilal Keskin Karakoyun  4 , Ceyhan Sayar  5 , Nuray Kepil  6 , Kanay Yararbas  5   7 , Omer Faruk Beser  3 , Haluk Cokugras  8 , Fugen Cullu Cokugras  9
Affiliations

Genetic Background of Eosinophilic Esophagitis and Esophageal Atresia in Children

Ipek Ulkersoy et al. Dig Dis Sci. 2025 Aug.

Abstract

Background and aims: The pathophysiology of eosinophilic esophagitis (EoE) is associated with a strong heritability and esophageal-specific genetic variants. Patients with esophageal atresia (EA) may be at higher risk of developing EoE considering the recently discovered genetic similarities between these disorders. This study aimed to identify genetic mutations associated with EoE, explore their potential role in susceptibility to concurrent EA, and evaluate the relationship between these mutations, clinical course, and treatment response.

Methods: Whole-exome sequencing was performed to identify the potential genomic regions associated with an increased risk of these disorders, and the analysis was expanded for candidate genes.

Results: A total of 35 cases (EA + EoE +; n = 7) were included. Pathogenic mutations in genes associated with EoE were identified in 2 cases, while likely pathogenic variants were identified in 5 cases. No polymorphisms were detected in 5 cases. Variants of uncertain significance (VUS) were identified in genes associated with EoE in 18 cases and in candidate genes in 7 cases. Patients with VUS exhibited a high percentage of associated EA, increased rates of atopy, and a notable response to treatment. The duration of the clinical response was significantly longer in individuals without genetic mutations (p-value:0.006). Among the isolated EoE cases, 50% had variants in genes previously associated with EoE, whereas in EA + EoE + cases, this rate increased to 71%, suggesting a stronger genetic predisposition in EA + EoE + cases.

Conclusion: Our study highlights the role of genetic mutations in the etiology of EoE. The identification of novel gene variants and new insights into etiopathogenesis are anticipated to enhance diagnosis, screening, and treatment strategies.

Keywords: Eosinophilic esophagitis; Esophageal atresia; Functional analysis; Whole-exome sequencing.

PubMed Disclaimer

Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethical approval: The study was conducted in accordance with the Declaration of Helsinki (2013 revision) following ethical committee approval (Istanbul University-Cerrahpasa Rectorate Clinical Research Ethics Committee; August 9, 2023; No: 753285). Written informed consent was obtained from parents/legal guardians and patients ≥ 12 years.

References

    1. Amil-Dias J, Oliva S, Papadopoulou A, Thomson M, Gutiérrez-Junquera C, Kalach N et al. Diagnosis and management of eosinophilic esophagitis in children: an update from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr. 2024;79:394–437. - PubMed
    1. Underwood B, Troutman TD, Schwartz JT. Breaking down the complex pathophysiology of eosinophilic esophagitis. Ann Allergy Asthma Immunol. 2023;130:28–39. - PubMed
    1. Blanchard C. Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis. J Clin Invest. 2006;116:536–547. - PubMed - PMC
    1. Blanchard C, Mingler MK, Vicario M, Abonia JP, Wu YY, Lu TX et al. IL-13 involvement in eosinophilic esophagitis: transcriptome analysis and reversibility with glucocorticoids. J Allergy Clin Immunol. 2007;120:1292–1300. - PubMed
    1. Sherrill JD, Kc K, Wu D, Djukic Z, Caldwell JM, Stucke EM et al. Desmoglein-1 regulates esophageal epithelial barrier function and immune responses in eosinophilic esophagitis. Mucosal Immunol. 2014;7:718–729. - PubMed

LinkOut - more resources