Genetic and demographic features of X-linked agammaglobulinemia in Eastern and Central Europe: A cohort study

B. Tóth, Alla Volokha, Alexander Mihas, Malgorzata Pac, Ewa Bernatowska, Irina Kondratenko, Alexander Polyakov, M. Erdős, Srdjan Pasic, Michaela Bataneant, Anna Szaflarska, Kristina Mironska, Darko Richter, Katarina Stavrik, Tadej Avcin, Gabriella Márton, K. Nagy, Beáta Dérfalvi, Miklós Szolnoky, Ágnes KalmárMichael Belevtsev, Marina Guseva, Aurica Rugina, Gergely Kriván, László Timár, Zoltán Nyul, Bernadett Mosdósi, Lidija Kareva, Sonja Peova, Liudmyla Chernyshova, Ioan Gherghina, Margit Serban, Mary Ellen Conley, Luigi D. Notarangelo, C. I Edvard Smith, Jacques van Dongen, Mirjam van der Burg, L. Máródi

Research output: Article

37 Citations (Scopus)

Abstract

Primary immunodeficiency disorders are a recognized public health problem worldwide. The prototype of these conditions is X-linked agammaglobulinemia (XLA) or Bruton's disease. XLA is caused by mutations in Bruton's tyrosine kinase gene (BTK), preventing B cell development and resulting in the almost total absence of serum immunoglobulins. The genetic profile and prevalence of XLA have not previously been studied in Eastern and Central European (ECE) countries. We studied the genetic and demographic features of XLA in Belarus, Croatia Hungary, Poland, Republic of Macedonia, Romania, Russia, Serbia, Slovenia, and Ukraine. We collected clinical, immunological, and genetic information for 122 patients from 109 families. The BTK gene was sequenced from the genomic DNA of patients with a high susceptibility to infection, almost no CD19+ peripheral blood B cells, and low or undetectable levels of serum immunoglobulins M, G, and A, compatible with a clinical and immunological diagnosis of XLA. BTK sequence analysis revealed 98 different mutations, 46 of which are reported for the first time here. The mutations included single nucleotide changes in the coding exons (35 missense and 17 nonsense), 23 splicing defects, 13 small deletions, 7 large deletions, and 3 insertions. The mutations were scattered throughout the BTK gene and most frequently concerned the SH1 domain; no missense mutation was detected in the SH3 domain. The prevalence of XLA in ECE countries (total population 145,530,870) was found to be 1 per 1,399,000 individuals. This report provides the first comprehensive overview of the molecular genetic and demographic features of XLA in Eastern and Central Europe.

Original languageEnglish
Pages (from-to)2140-2146
Number of pages7
JournalMolecular Immunology
Volume46
Issue number10
DOIs
Publication statusPublished - jún. 2009

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Eastern Europe
Cohort Studies
Demography
Genes
Mutation
src Homology Domains
Macedonia (Republic)
B-Lymphocytes
Republic of Belarus
Slovenia
Serbia
Ukraine
Romania
Immunologic Tests
Croatia
Hungary
Russia
Missense Mutation
Poland
Bruton type agammaglobulinemia

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Cite this

Genetic and demographic features of X-linked agammaglobulinemia in Eastern and Central Europe : A cohort study. / Tóth, B.; Volokha, Alla; Mihas, Alexander; Pac, Malgorzata; Bernatowska, Ewa; Kondratenko, Irina; Polyakov, Alexander; Erdős, M.; Pasic, Srdjan; Bataneant, Michaela; Szaflarska, Anna; Mironska, Kristina; Richter, Darko; Stavrik, Katarina; Avcin, Tadej; Márton, Gabriella; Nagy, K.; Dérfalvi, Beáta; Szolnoky, Miklós; Kalmár, Ágnes; Belevtsev, Michael; Guseva, Marina; Rugina, Aurica; Kriván, Gergely; Timár, László; Nyul, Zoltán; Mosdósi, Bernadett; Kareva, Lidija; Peova, Sonja; Chernyshova, Liudmyla; Gherghina, Ioan; Serban, Margit; Conley, Mary Ellen; Notarangelo, Luigi D.; Smith, C. I Edvard; van Dongen, Jacques; van der Burg, Mirjam; Máródi, L.

In: Molecular Immunology, Vol. 46, No. 10, 06.2009, p. 2140-2146.

Research output: Article

Tóth, B, Volokha, A, Mihas, A, Pac, M, Bernatowska, E, Kondratenko, I, Polyakov, A, Erdős, M, Pasic, S, Bataneant, M, Szaflarska, A, Mironska, K, Richter, D, Stavrik, K, Avcin, T, Márton, G, Nagy, K, Dérfalvi, B, Szolnoky, M, Kalmár, Á, Belevtsev, M, Guseva, M, Rugina, A, Kriván, G, Timár, L, Nyul, Z, Mosdósi, B, Kareva, L, Peova, S, Chernyshova, L, Gherghina, I, Serban, M, Conley, ME, Notarangelo, LD, Smith, CIE, van Dongen, J, van der Burg, M & Máródi, L 2009, 'Genetic and demographic features of X-linked agammaglobulinemia in Eastern and Central Europe: A cohort study', Molecular Immunology, vol. 46, no. 10, pp. 2140-2146. https://doi.org/10.1016/j.molimm.2009.03.012
Tóth, B. ; Volokha, Alla ; Mihas, Alexander ; Pac, Malgorzata ; Bernatowska, Ewa ; Kondratenko, Irina ; Polyakov, Alexander ; Erdős, M. ; Pasic, Srdjan ; Bataneant, Michaela ; Szaflarska, Anna ; Mironska, Kristina ; Richter, Darko ; Stavrik, Katarina ; Avcin, Tadej ; Márton, Gabriella ; Nagy, K. ; Dérfalvi, Beáta ; Szolnoky, Miklós ; Kalmár, Ágnes ; Belevtsev, Michael ; Guseva, Marina ; Rugina, Aurica ; Kriván, Gergely ; Timár, László ; Nyul, Zoltán ; Mosdósi, Bernadett ; Kareva, Lidija ; Peova, Sonja ; Chernyshova, Liudmyla ; Gherghina, Ioan ; Serban, Margit ; Conley, Mary Ellen ; Notarangelo, Luigi D. ; Smith, C. I Edvard ; van Dongen, Jacques ; van der Burg, Mirjam ; Máródi, L. / Genetic and demographic features of X-linked agammaglobulinemia in Eastern and Central Europe : A cohort study. In: Molecular Immunology. 2009 ; Vol. 46, No. 10. pp. 2140-2146.
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abstract = "Primary immunodeficiency disorders are a recognized public health problem worldwide. The prototype of these conditions is X-linked agammaglobulinemia (XLA) or Bruton's disease. XLA is caused by mutations in Bruton's tyrosine kinase gene (BTK), preventing B cell development and resulting in the almost total absence of serum immunoglobulins. The genetic profile and prevalence of XLA have not previously been studied in Eastern and Central European (ECE) countries. We studied the genetic and demographic features of XLA in Belarus, Croatia Hungary, Poland, Republic of Macedonia, Romania, Russia, Serbia, Slovenia, and Ukraine. We collected clinical, immunological, and genetic information for 122 patients from 109 families. The BTK gene was sequenced from the genomic DNA of patients with a high susceptibility to infection, almost no CD19+ peripheral blood B cells, and low or undetectable levels of serum immunoglobulins M, G, and A, compatible with a clinical and immunological diagnosis of XLA. BTK sequence analysis revealed 98 different mutations, 46 of which are reported for the first time here. The mutations included single nucleotide changes in the coding exons (35 missense and 17 nonsense), 23 splicing defects, 13 small deletions, 7 large deletions, and 3 insertions. The mutations were scattered throughout the BTK gene and most frequently concerned the SH1 domain; no missense mutation was detected in the SH3 domain. The prevalence of XLA in ECE countries (total population 145,530,870) was found to be 1 per 1,399,000 individuals. This report provides the first comprehensive overview of the molecular genetic and demographic features of XLA in Eastern and Central Europe.",
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AU - Avcin, Tadej

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AU - Nagy, K.

AU - Dérfalvi, Beáta

AU - Szolnoky, Miklós

AU - Kalmár, Ágnes

AU - Belevtsev, Michael

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AU - Mosdósi, Bernadett

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AU - Chernyshova, Liudmyla

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AU - Serban, Margit

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AU - Notarangelo, Luigi D.

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N2 - Primary immunodeficiency disorders are a recognized public health problem worldwide. The prototype of these conditions is X-linked agammaglobulinemia (XLA) or Bruton's disease. XLA is caused by mutations in Bruton's tyrosine kinase gene (BTK), preventing B cell development and resulting in the almost total absence of serum immunoglobulins. The genetic profile and prevalence of XLA have not previously been studied in Eastern and Central European (ECE) countries. We studied the genetic and demographic features of XLA in Belarus, Croatia Hungary, Poland, Republic of Macedonia, Romania, Russia, Serbia, Slovenia, and Ukraine. We collected clinical, immunological, and genetic information for 122 patients from 109 families. The BTK gene was sequenced from the genomic DNA of patients with a high susceptibility to infection, almost no CD19+ peripheral blood B cells, and low or undetectable levels of serum immunoglobulins M, G, and A, compatible with a clinical and immunological diagnosis of XLA. BTK sequence analysis revealed 98 different mutations, 46 of which are reported for the first time here. The mutations included single nucleotide changes in the coding exons (35 missense and 17 nonsense), 23 splicing defects, 13 small deletions, 7 large deletions, and 3 insertions. The mutations were scattered throughout the BTK gene and most frequently concerned the SH1 domain; no missense mutation was detected in the SH3 domain. The prevalence of XLA in ECE countries (total population 145,530,870) was found to be 1 per 1,399,000 individuals. This report provides the first comprehensive overview of the molecular genetic and demographic features of XLA in Eastern and Central Europe.

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