ORIGINAL RESEARCH article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1584681
This article is part of the Research TopicMonogenic Inborn Errors of Immunity Associated with AtopyView all 3 articles
Clinical and Molecular Findings in Actin-related Inborn Errors of Immunity: The Middle East and North Africa Registry
Provisionally accepted- 1Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Alborz, Iran
- 2Shahid Beheshti University of Medical Sciences, Tehran, Tehran, Iran
- 3Tehran University of Medical Sciences, Tehran, Tehran, Iran
- 4University of Algiers, Algiers, Algiers, Algeria
- 5Faculty of Medicine, Ankara University, Ankara, Sakarya, Türkiye
- 6Dr.Behçet Uz Children's Hospital, University of Health Sciences, Konak, Izmir, Türkiye
- 7School of Medicine, Marmara University, Maltepe, Istanbul, Türkiye
- 8Faculty of Medicine, Istanbul University, Istanbul, Istanbul, Türkiye
- 9Ege University, Bornova, İzmir, Türkiye
- 10Necmettin Erbakan University, Karatay, Konya, Türkiye
- 11Pasteur Institute of Tunis, Tunis, Tunisia
- 12Mansoura University, Mansoura, Dakahlia, Egypt
- 13Department of Pediatrics, Tawam Hospital, Al Ain, United Arab Emirates
- 14Tawam Hospital, Al Ain, Abu Dhabi, United Arab Emirates
- 15Azerbaijan Medical University, Baku, Azerbaijan
- 16United Arab Emirates University, Al-Ain, Abu Dhabi, United Arab Emirates
- 17American University of Beirut Medical Center, Beirut, Beyrouth, Lebanon
- 18Lebanese American University, Beirut, Beirut, Lebanon
- 19Saint Joseph University, Beirut, Beirut, Lebanon
- 20Sultan Qaboos University Hospital, Muscat, Oman
- 21Kuwait University, Kuwait City, Kuwait
- 22Queen Rania al-Abdullah Center for Environmental Science & Technology, Jordan University of Science and Technology, Irbid, Irbid, Jordan
- 23Bursa Uludağ University, Bursa, Bursa, Türkiye
- 24Isfahan University of Medical Sciences, Isfahan, Isfahan, Iran
- 25Shiraz University of Medical Sciences, Shiraz, Fars, Iran
- 26Mashhad University of Medical Sciences, Mashhad, Razavi Khorasan, Iran
- 27Medical University of Vienna, Vienna, Vienna, Austria
- 28University of Washington, Seattle, Washington, United States
- 29Department of Medical Biochemistry and Biophysics, Karolinska Institutet (KI), Stockholm, Sweden
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Background: The majority of monogenic inborn errors of immunity presenting as actinopathies were reported originally from the Middle East and North Africa (MENA) countries indicating a high prevalence of these entities in the region. However, their prognosis is unclear due to rarity and lack of comprehensive treatment outcomes.We evaluated clinical, immunological, and genetic abnormalities associated with 15 genetic entities of actinopathies. Based on the function of mutant genes in actin-regulatory pathways, patients were classified into CDC42-and RAC2-related subcategories.Results: A total of 503 individuals (29.5% females) from 17 countries were considered with a median age of 120 months. Although most patients presented initially with allergic phenotypes (42.1%), the most prevalent manifestations throughout the lifespan were infection in respiratory tracts (72.1%). Primary clinical diagnosis was mainly combined immunodeficiencies (48.3%) and the majority of cases were molecularly assigned to the CDC42 pathway (64.8%). The most common genetic defects were reported within the DOCK8 (n=209) followed by the WAS (n=94) and the CARMIL2 (n=15) genes. Hematopoietic stem cell transplantation (HSCT) was conducted on 24.0% of patients, with significantly improved survival in patients with defects in WAS, DOCK8 and DOCK2. Overall mortality was 23.0%, mainly due to sepsis and malignancy.Patients with defects in RAC2-associated regulators of actin usually present with late-onset symptoms due to normal immune profiles, but a higher rate of EBV and HPV infections, autoimmune cytopenia, asthma, and lymphoproliferation compared to defects in the CDC42 pathway. The severity of mutations in patients of the CDC42 group helps to estimate the prognosis of the disease and prioritization of HSCT.
Keywords: Actinopathies, Thrombocytopenia, Eosinophilia, inborn errors of immunity, Primary immunodeficiency, genetic, Immune dysregulation
Received: 28 Feb 2025; Accepted: 04 Jul 2025.
Copyright: © 2025 Chavoshzadeh, Fallah, Zeinali, Sharafian, Delavari, Mesdaghi, Djidjik, Belaid, Ikinciogullari, Haskoloğlu, Dogu, Genel, Gulez, Baris, Ozen, Karakoc-Aydiner, Kiykim, Meric, Kutukculer, Aygun, Aksu, Neslihan, Geyik, Keles, Reisli, Nail, BOUKARI, Hakem, Belbouab, Barbouche, Ben- Mustapha, MEKKI, Ben-Ali, Sobh, Elnagdy, Djenouhat, Tahiat, Shendi, Alkuwaiti, Nasrullayeva, Al Farsi, Alsukaiti, Massaad, Mehawej, Mégarbané, Irani, Elghazali, Al-Tamemi, Khalifa, Alzyoud, Kilic, Kose, Khodaverdy, Shamsian, Eslami, Momen, Sherkat, Aleyasin, Esmaeilzadeh, Ahanchian, Salami, Fekrvand, Dupre, Ochs, Rezaei, Al-Herz and Abolhassani. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Shahrzad Fallah, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, 1546815514, Alborz, Iran
Hassan Abolhassani, Department of Medical Biochemistry and Biophysics, Karolinska Institutet (KI), Stockholm, Sweden
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