1/15/2024 0 Comments X linked agammaglobulinemiaAmong all the XLA causative mutations, 15% to 20% are known to occur de novo ( 3). All domains may be affected by mutations. The BTK gene is located in the Xq22 region of the X chromosome and has five distinct structural domains: Pleckstrin homology (PH), Tec homology (TH), Src homology (SH3), SH2, and catalytic kinase (SH1) domains. In particular, it promotes preB cell expansion at the preB1 to preB2 stage ( 1, 2). X-linked Agammaglobulinemia (XLA) is a primary immunodeficiency disease caused by a mutation in the Bruton Tyrosine Kinase ( BTK) gene that encodes an essential protein involved in B-cell maturation. High serum IgE levels could be a sign of a mild phenotype, but their role and the mechanisms underlying their production in XLA need to be clarified. XLA patients rarely present with allergic manifestations, which could warrant further investigation. Further immunological tests (BTK expression, functional “ in vitro” B cell proliferation upon CpG stimulation, B cell subset analysis) explained these findings as possible manifestations of a mild XLA phenotype. Thus, total serum IgE levels were measured and detected over the normal range, and specific allergic investigations showed sensitization to dust mites. He never suffered severe infections, but at two years of age, he developed persistent rhinitis. The disease was genetically diagnosed at birth due to a family history of XLA, but during follow up, it was characterized by a CD19+ B cell percentage consistently greater than 2%. In this report we present a unique case of a young patient affected by XLA. Little is known about genotype-phenotype correlation in this disorder, and factors influencing the phenotype of XLA are not clearly understood. All domains may be affected by the mutation, and the many genotypes are associated with a wide range of clinical presentations. Bruton Tyrosine Kinase ( BTK) gene encodes a cytoplasmic tyrosine kinase involved in the B cell maturation and its mutation, blocking B cell differentiation at the pre-B cell stage, and is responsible for XLA. X-linked Agammaglobulinemia (XLA) is a rare genetic disorder of B-lymphocyte differentiation, characterized by the absence or paucity of circulating B cells, markedly reduced levels of all serum immunoglobulin isotypes and lack of specific antibody production. 6Medical Genetics Unit, S.Orsola-Malpighi University Hospital, Bologna, Italy.5B Cell Physiopathology Unit, Immunology Research Area, Bambino Gesù Children Hospital, Rome, Italy. 4Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.3Flow Cytometry Unit, Clinical Chemistry Laboratory, Spedali Civili Hospital, Brescia, Italy.Nocivelli” Institute for Molecular Medicine Spedali Civili Hospital, Brescia, Italy 2Cytogenetic and Medical Genetics Unit, “A.1Department of Pediatrics, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.Bianca Cinicola 1* Andrea Uva 1 Lucia Leonardi 1 Daniele Moratto 2,3 Silvia Giliani 2,4 Rita Carsetti 5 Simona Ferrari 6 Anna Maria Zicari 1† Marzia Duse 1†
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