J Clin Immunol (2014) 34:425–427 DOI 10.1007/s10875-014-0033-4
ASTUTE CLINICIAN REPORT
Autosomal Recessive Agammaglobulinemia: The Third Case of Igβ Deficiency Due to a Novel Non-sense Mutation Vassilios Lougaris & Massimiliano Vitali & Manuela Baronio & Daniele Moratto & Giacomo Tampella & Augusto Biasini & Raffaele Badolato & Alessandro Plebani
Received: 13 February 2014 / Accepted: 27 March 2014 / Published online: 11 April 2014 # Springer Science+Business Media New York 2014
Abstract This study describes the third case worldwide of autosomal recessive agammaglobulinemia due to a novel nonsense mutation in Igβ presenting with neutropenia, ecthyma and mild respiratory infections. Keywords pre-BCR . Igβ . autosomal recessive agammaglobulinemia Abbreviations pre-BCR pre-B cell receptor complex Igβ Immunoglobulin-associated beta
Astute Clinician Report Igβ, together with Igα, represent the signaling components of the pre-B cell receptor complex (pre-BCR), a receptor complex expressed on B cells during bone marrow development [1–3]. Defects in any of the components of the pre-BCR or downstream signaling elements have been demonstrated to cause a developmental arrest of B cells in the bone marrow leading therefore to the absence of B cells in the periphery and consequently to the development of agammaglobulinemia [4, 5]. The autosomal recessive forms of agammaglobulinemia are very rare and are caused by defects in the genes encoding for: mu heavy chain, Igα, Igβ, λ5, BLNK and p85a (PI3K) V. Lougaris (*) : M. Vitali : M. Baronio : D. Moratto : G. Tampella : R. Badolato : A. Plebani Department of Clinical and Experimental Sciences, Pediatrics Clinic and Institute for Molecular Medicine “A. Nocivelli”, University of Brescia, Spedali Civili di Brescia, Brescia, Italy e-mail: [email protected] A. Biasini Maternal-Infantile Department, Pediatrics Clinic, Cesena, Italy
[6–16]. We report on the third patient worldwide affected with Igβ deficiency due to a novel null mutation presenting with neutropenia, ecthyma and respiratory infections. The patient was born to consanguineous parents of Tunisian ethnicity and came to our center at 15 months of age. Her clinical history included three mild upper respiratory tract infections that were treated with oral antibiotics. At the age of 14 months, the patient was admitted for fever and ecthyma of the left gluteus. White blood cell count showed severe neutropenia (absolute neutrophil count: 10 cells/mm3). Skin biopsy revealed Staphylococcus aureus leading therefore to the adjustment of initial antibiotic treatment with amoxicilline + clavulanic acid to clindamycin and cephtazidime. Based on the finding of severe neutropenia, further immunological investigations were undertaken. Immunoglobulin serum levels were tested revealing severe hypogammaglobulinemia: IgG:
ASTUTE CLINICIAN REPORT
Autosomal Recessive Agammaglobulinemia: The Third Case of Igβ Deficiency Due to a Novel Non-sense Mutation Vassilios Lougaris & Massimiliano Vitali & Manuela Baronio & Daniele Moratto & Giacomo Tampella & Augusto Biasini & Raffaele Badolato & Alessandro Plebani
Received: 13 February 2014 / Accepted: 27 March 2014 / Published online: 11 April 2014 # Springer Science+Business Media New York 2014
Abstract This study describes the third case worldwide of autosomal recessive agammaglobulinemia due to a novel nonsense mutation in Igβ presenting with neutropenia, ecthyma and mild respiratory infections. Keywords pre-BCR . Igβ . autosomal recessive agammaglobulinemia Abbreviations pre-BCR pre-B cell receptor complex Igβ Immunoglobulin-associated beta
Astute Clinician Report Igβ, together with Igα, represent the signaling components of the pre-B cell receptor complex (pre-BCR), a receptor complex expressed on B cells during bone marrow development [1–3]. Defects in any of the components of the pre-BCR or downstream signaling elements have been demonstrated to cause a developmental arrest of B cells in the bone marrow leading therefore to the absence of B cells in the periphery and consequently to the development of agammaglobulinemia [4, 5]. The autosomal recessive forms of agammaglobulinemia are very rare and are caused by defects in the genes encoding for: mu heavy chain, Igα, Igβ, λ5, BLNK and p85a (PI3K) V. Lougaris (*) : M. Vitali : M. Baronio : D. Moratto : G. Tampella : R. Badolato : A. Plebani Department of Clinical and Experimental Sciences, Pediatrics Clinic and Institute for Molecular Medicine “A. Nocivelli”, University of Brescia, Spedali Civili di Brescia, Brescia, Italy e-mail: [email protected] A. Biasini Maternal-Infantile Department, Pediatrics Clinic, Cesena, Italy
[6–16]. We report on the third patient worldwide affected with Igβ deficiency due to a novel null mutation presenting with neutropenia, ecthyma and respiratory infections. The patient was born to consanguineous parents of Tunisian ethnicity and came to our center at 15 months of age. Her clinical history included three mild upper respiratory tract infections that were treated with oral antibiotics. At the age of 14 months, the patient was admitted for fever and ecthyma of the left gluteus. White blood cell count showed severe neutropenia (absolute neutrophil count: 10 cells/mm3). Skin biopsy revealed Staphylococcus aureus leading therefore to the adjustment of initial antibiotic treatment with amoxicilline + clavulanic acid to clindamycin and cephtazidime. Based on the finding of severe neutropenia, further immunological investigations were undertaken. Immunoglobulin serum levels were tested revealing severe hypogammaglobulinemia: IgG:
