Cohort of Iranian Patients with Congenital Agammaglobulinemia: Mutation Analysis and Novel Gene Defects

Hassan Abolhassani, Massimiliano Vitali, Vassilios Lougaris, Silvia Giliani, Nima Parvaneh, Leila Parvaneh, Babak Mirminachi, Taher Cheraghi, Hosseinali Khazaei, Seyed Alireza Mahdaviani, Fatemeh Kiaei, Naiimeh Tavakolinia, Javad Mohammadi, Babak Negahdari, Nima Rezaei, Lennart Hammarstrom, Alessandro Plebani and Asghar Aghamohammadi

Pediatric Respiratory Diseases Research Centre, NRITLD, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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.
Keywords: Bruton’s tyrosine kinase; X-linked agammaglobulinemia; Autosomal recessive agammaglobulinemia; Genotype-phenotype correlation; Long-term cohort

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EXPERT REVIEW OF CLINICAL IMMUNOLOGY, 2016; 12(4): 479–486