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

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.

KEYWORDS:

• Bruton’s tyrosine kinase
• X-linked agammaglobulinemia
• Autosomal recessive agammaglobulinemia
• Genotype-phenotype correlation
• Long-term cohort

Financial & competing interests disclosure

The research leading to these results has received funding from the European Community’s Seventh Framework Programme FP7/2007-2013 under grant agreement no 201549 (EURO-PADnet HEALTH-F2-2008-201549) and also received funding from the “Fondazione C. Golgi”, Brescia. L Parvaneh is a postdoctoral research fellow at Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences. She is supported by a postdoctoral fellowship from the Iran’s National Elites Foundation (INEF). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Supplementary Material

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