Clinical and Genetic Study of X-linked Agammaglobulinemia Patients (The Benefit of Early Diagnosis)

  • Zahra Alizadeh Immunology, Asthma, and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  • Parisa Dashti Immunology, Asthma, and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  • Marzieh Mazinani Immunology, Asthma, and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  • Maryam Nourizadeh Immunology, Asthma, and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  • Leila Shakerian Immunology, Asthma, and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  • Shaghayegh Tajik Immunology, Asthma, and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  • Masoud Movahedi Department of Allergy and Clinical Immunology, Pediatrics Center of Excellence, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran
  • Setareh Mamishi Department of Infectious Diseases, Pediatrics Center of Excellence, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran AND Pediatric Infectious Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran
  • Zahra Pourpak Immunology, Asthma, and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
  • Mohammad Reza Fazlollahi Immunology, Asthma, and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
Keywords:
Bruton tyrosine kinase, Early diagnosis, Mutation, X-linked agammaglobulinemia

Abstract

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by genetic defects in the Bruton tyrosine kinase (Btk) gene. XLA is characterized as an antibody deficiency by recurrent bacterial infections, the absence of peripheral B cells, and profound reductions in all immunoglobulin isotypes. This study aims to report the clinical and genetic features of five Iranian patients with XLA.
Five male cases with recurrent bacterial infection entered this study based on clinical evaluation and Immunological screening tests. The levels of T-cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) were also measured in dried blood spot (DBS) samples. Sanger sequencing was applied to PCR products of DNA samples of the patients for genetic studies.
All patients were from unrelated families with a mean age of 6.7 years (2.5-11) at the time of diagnosis with 4.8 mean years of delay in diagnosis. The most frequent clinical manifestations were recurrent respiratory infections and arthritis. In these patients, five previously reported mutations were found including four mutations (p.Q496X, p.Q497X, p.R520X, and p.R641H) in the Kinase domain besides one mutation (p.L37P) in the pleckstrin homology (PH) domain. Evaluations of KREC and TREC level in patients’ DBS showed low-to-undetectable copies of KREC (0-2 copies/3.2mm DBS) with normal copies of TREC.
As patients with XLA have complete immunoglobulin defects and develop severe and recurrent infections, early diagnosis would be beneficial for the improvement of their quality of life. The study results may provide valuable information for the diagnosis, genetic counseling and prenatal diagnosis for the patients and their family members and emphasize performing KREC as an early diagnostic test in patients with XLA.

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Published
2020-06-23
How to Cite
1.
Alizadeh Z, Dashti P, Mazinani M, Nourizadeh M, Shakerian L, Tajik S, Movahedi M, Mamishi S, Pourpak Z, Fazlollahi MR. Clinical and Genetic Study of X-linked Agammaglobulinemia Patients (The Benefit of Early Diagnosis). Iran J Allergy Asthma Immunol. 19(3):305-309.
Section
Original Article(s)