A novel CARD11 heterozygous missense variant in a CADINS patient
Background: CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) is developed as a result of heterozygous loss-of-function variants in CARD11 that function as strong dominant-negative alleles. In lymphocytes, CARD11 encodes a scaffold protein that links activation of the an...
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Elsevier
2025-05-01
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| Series: | Journal of Allergy and Clinical Immunology: Global |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772829325000621 |
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| author | Randa S. AlYafie, PhD Mehdi Adeli, MD Dinesh Velayutham, PhD Salim Bougarn, PhD Manar Ata, MSc Fatima Al-Ali, MRes Evonne Chin-Smith, PhD Bradly M. Bauman, PhD Andrew L. Snow, PhD Bertrand Boisson, PhD Nico Marr, PhD Nicholas van Panhuys, PhD Andrea Guennoun, PhD Puthen Veettil Jithesh, PhD |
| author_facet | Randa S. AlYafie, PhD Mehdi Adeli, MD Dinesh Velayutham, PhD Salim Bougarn, PhD Manar Ata, MSc Fatima Al-Ali, MRes Evonne Chin-Smith, PhD Bradly M. Bauman, PhD Andrew L. Snow, PhD Bertrand Boisson, PhD Nico Marr, PhD Nicholas van Panhuys, PhD Andrea Guennoun, PhD Puthen Veettil Jithesh, PhD |
| author_sort | Randa S. AlYafie, PhD |
| collection | DOAJ |
| description | Background: CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) is developed as a result of heterozygous loss-of-function variants in CARD11 that function as strong dominant-negative alleles. In lymphocytes, CARD11 encodes a scaffold protein that links activation of the antigen receptor with downstream signaling. Patients with CADINS generally experience severe atopic dermatitis, asthma, recurrent pneumonia and other upper respiratory tract infections, skin infections, and allergies to a variety of dietary and environmental antigens. Additionally, patients experience elevated levels of serum IgE, but low to normal levels of other immunoglobulin types. Objective: We performed genetic diagnosis of a patient of nonconsanguineous descent presenting at 11 years of age with severe atopic dermatitis, asthma, food allergy, skin and recurrent infections, and an extremely elevated level of serum IgE. Methods: We performed whole genome sequencing of samples obtained from the patient and his entire family. Results: Clinical, laboratory, genetic, and functional findings suggested CADINS. Genetic evaluation revealed a novel heterozygous missense variant (c.2913C>G, p.Cys971Trp) in the CARD11 gene as the potential underlying defect. Expression of CARD11 variant–stimulated constitutive NF-κB activity in T-cell lines demonstrated both loss-of-function and dominant-negative activity. Conclusion: A novel germline heterozygous missense variant (c.2913C>G) in CARD11 potentially leads to CADINS. |
| format | Article |
| id | doaj-art-2be1e1de63cb4cbda5b48da5c301e701 |
| institution | OA Journals |
| issn | 2772-8293 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Allergy and Clinical Immunology: Global |
| spelling | doaj-art-2be1e1de63cb4cbda5b48da5c301e7012025-08-20T01:51:13ZengElsevierJournal of Allergy and Clinical Immunology: Global2772-82932025-05-014210046110.1016/j.jacig.2025.100461A novel CARD11 heterozygous missense variant in a CADINS patientRanda S. AlYafie, PhD0Mehdi Adeli, MD1Dinesh Velayutham, PhD2Salim Bougarn, PhD3Manar Ata, MSc4Fatima Al-Ali, MRes5Evonne Chin-Smith, PhD6Bradly M. Bauman, PhD7Andrew L. Snow, PhD8Bertrand Boisson, PhD9Nico Marr, PhD10Nicholas van Panhuys, PhD11Andrea Guennoun, PhD12Puthen Veettil Jithesh, PhD13College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar; Research Department, Sidra Medicine, Doha, QatarDepartment of Allergy and Immunology, Sidra Medicine, Doha, Qatar; Hamad Medical Corporation, Doha, QatarCollege of Health and Life Sciences, Hamad Bin Khalifa University, Doha, QatarResearch Department, Sidra Medicine, Doha, QatarResearch Department, Sidra Medicine, Doha, QatarResearch Department, Sidra Medicine, Doha, QatarResearch Department, Sidra Medicine, Doha, QatarDepartment of Pharmacology & Molecular Therapeutics, Uniformed Services, University of the Health Sciences, Bethesda, MdDepartment of Pharmacology & Molecular Therapeutics, Uniformed Services, University of the Health Sciences, Bethesda, MdThe Rockefeller University, New York, NYCollege of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar; Research Department, Sidra Medicine, Doha, Qatar; Corresponding authors: Andrea Guennoun, PhD, Nicholas van Panhuys, PhD, or Nico Marr, PhD, Research Department, Sidra Medicine, Doha, Qatar.College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar; Research Department, Sidra Medicine, Doha, Qatar; Corresponding authors: Andrea Guennoun, PhD, Nicholas van Panhuys, PhD, or Nico Marr, PhD, Research Department, Sidra Medicine, Doha, Qatar.Research Department, Sidra Medicine, Doha, Qatar; Corresponding authors: Andrea Guennoun, PhD, Nicholas van Panhuys, PhD, or Nico Marr, PhD, Research Department, Sidra Medicine, Doha, Qatar.College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar; Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom; Puthen Veettil Jithesh, PhD, College of Health & Life Sciences, Hamad Bin Khalifa University, C-147, Penrose House, PO Box 34110, Education City, Doha, Qatar.Background: CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) is developed as a result of heterozygous loss-of-function variants in CARD11 that function as strong dominant-negative alleles. In lymphocytes, CARD11 encodes a scaffold protein that links activation of the antigen receptor with downstream signaling. Patients with CADINS generally experience severe atopic dermatitis, asthma, recurrent pneumonia and other upper respiratory tract infections, skin infections, and allergies to a variety of dietary and environmental antigens. Additionally, patients experience elevated levels of serum IgE, but low to normal levels of other immunoglobulin types. Objective: We performed genetic diagnosis of a patient of nonconsanguineous descent presenting at 11 years of age with severe atopic dermatitis, asthma, food allergy, skin and recurrent infections, and an extremely elevated level of serum IgE. Methods: We performed whole genome sequencing of samples obtained from the patient and his entire family. Results: Clinical, laboratory, genetic, and functional findings suggested CADINS. Genetic evaluation revealed a novel heterozygous missense variant (c.2913C>G, p.Cys971Trp) in the CARD11 gene as the potential underlying defect. Expression of CARD11 variant–stimulated constitutive NF-κB activity in T-cell lines demonstrated both loss-of-function and dominant-negative activity. Conclusion: A novel germline heterozygous missense variant (c.2913C>G) in CARD11 potentially leads to CADINS.http://www.sciencedirect.com/science/article/pii/S2772829325000621CARD11CADINSeczemaasthmafood allergiesloss-of-function variant |
| spellingShingle | Randa S. AlYafie, PhD Mehdi Adeli, MD Dinesh Velayutham, PhD Salim Bougarn, PhD Manar Ata, MSc Fatima Al-Ali, MRes Evonne Chin-Smith, PhD Bradly M. Bauman, PhD Andrew L. Snow, PhD Bertrand Boisson, PhD Nico Marr, PhD Nicholas van Panhuys, PhD Andrea Guennoun, PhD Puthen Veettil Jithesh, PhD A novel CARD11 heterozygous missense variant in a CADINS patient Journal of Allergy and Clinical Immunology: Global CARD11 CADINS eczema asthma food allergies loss-of-function variant |
| title | A novel CARD11 heterozygous missense variant in a CADINS patient |
| title_full | A novel CARD11 heterozygous missense variant in a CADINS patient |
| title_fullStr | A novel CARD11 heterozygous missense variant in a CADINS patient |
| title_full_unstemmed | A novel CARD11 heterozygous missense variant in a CADINS patient |
| title_short | A novel CARD11 heterozygous missense variant in a CADINS patient |
| title_sort | novel card11 heterozygous missense variant in a cadins patient |
| topic | CARD11 CADINS eczema asthma food allergies loss-of-function variant |
| url | http://www.sciencedirect.com/science/article/pii/S2772829325000621 |
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