Hassan Abolhassani1,2, Massimiliano Vitali3, Vassilios Lougaris3, Silvia Giliani3, Nima Parvaneh1, Leila Parvaneh1, Babak Mirminachi1, Taher Cheraghi4, Hosseinali Khazaei5, Seyed Alireza Mahdaviani6, Fatemeh Kiaei1, Naiimeh Tavakolinia1, Javad Mohammadi7, Babak Negahdari8, Nima Rezaei1, Lennart Hammarstrom2, Alessandro Plebani3, Asghar Aghamohammadi1. 1. a Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran. 2. b Division of Clinical Immunology, Department of Laboratory Medicine , Karolinska Institutet at Karolinska University Hospital Huddinge , Stockholm , Sweden. 3. c Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences , University of Brescia, Spedali Civili , Brescia , Italy. 4. d Department of Pediatrics , 17th Shahrivar Children's Hospital, Guilan University of Medical Sciences , Rasht , Iran. 5. e Department of Immunology and Hematology , Zahedan Medical, Sciences University , Zahedan , Iran. 6. f Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases , Shahid Beheshti University of Medical Sciences , Tehran , Iran. 7. g Department of Life Science, Faculty of New Science and Technology , University of Tehran , Tehran , Iran. 8. h School of Advanced Technologies in Medicine, Department of Medical Biotechnology , Tehran University of Medical Sciences , Tehran , Iran.
Abstract
OBJECTIVES: Impairment in early B-cell development can cause a predominantly antibody deficiency with severe depletion of peripheral B-cells. Mutations in the gene encoding for Bruton's-tyrosine-kinase (BTK) and the components of the pre-B-cell receptor complex or downstream signaling molecules have been related to this defect in patients with agammaglobulinemia. METHODS: Iranian patients with congenital agammaglobulinemia were included and the correlation between disease-causing mutations and parameters such as clinical and immunologic phenotypes were evaluated in available patients. RESULTS: Out of 87 patients, a molecular investigation was performed on 51 patients leading to identification of 39 cases with BTK (1 novel mutation), 5 cases of µ-heavy chain (3 novel mutations) and 1 case of Igα-deficiencies. CONCLUSION: Although there is no comprehensive correlation between type of responsible BTK mutation and severity of clinical phenotype, our data suggest that BTK-deficient and autosomal recessive agammaglobulinemia patients differ significantly regarding clinical/immunologic characteristics.
OBJECTIVES: Impairment in early B-cell development can cause a predominantly antibody deficiency with severe depletion of peripheral B-cells. Mutations in the gene encoding for Bruton's-tyrosine-kinase (BTK) and the components of the pre-B-cell receptor complex or downstream signaling molecules have been related to this defect in patients with agammaglobulinemia. METHODS: Iranian patients with congenital agammaglobulinemia were included and the correlation between disease-causing mutations and parameters such as clinical and immunologic phenotypes were evaluated in available patients. RESULTS: Out of 87 patients, a molecular investigation was performed on 51 patients leading to identification of 39 cases with BTK (1 novel mutation), 5 cases of µ-heavy chain (3 novel mutations) and 1 case of Igα-deficiencies. CONCLUSION: Although there is no comprehensive correlation between type of responsible BTK mutation and severity of clinical phenotype, our data suggest that BTK-deficient and autosomal recessive agammaglobulinemiapatients differ significantly regarding clinical/immunologic characteristics.
Authors: Asghar Aghamohammadi; Hassan Abolhassani; Necil Kutukculer; Steve G Wassilak; Mark A Pallansch; Samantha Kluglein; Jessica Quinn; Roland W Sutter; Xiaochuan Wang; Ozden Sanal; Tatiana Latysheva; Aydan Ikinciogullari; Ewa Bernatowska; Irina A Tuzankina; Beatriz T Costa-Carvalho; Jose Luis Franco; Raz Somech; Elif Karakoc-Aydiner; Surjit Singh; Liliana Bezrodnik; Francisco J Espinosa-Rosales; Anna Shcherbina; Yu-Lung Lau; Shigeaki Nonoyama; Fred Modell; Vicki Modell; Mohamed-Ridha Barbouche; Mark A McKinlay Journal: Front Immunol Date: 2017-06-13 Impact factor: 7.561