title: A new mutation that predicted a drastic alteration of the BTK protein function.
abstract: X-linked agammaglobulinemia (XLA) or Bruton disease is a relatively rare constitutionally immune disorder due to a genetic mutation of BTK (Bruton tyrosine kinase) gene which encodes for BTK protein. BTK is a signal-transducing protein expressed in hematopoietic lineages. The genetic disorder is responsible for B cell lymphocytes' maturation arrest. The humoral immunodeficiency caused by BTK mutation is linked with recurrent bacterial and viral infections. Genetic investigations of the prepositus as well as the other members of the family are necessary to characterize a mutation in BTK gene to confirm the diagnosis and reveal a hereditary transmission or de novo mutation. Authors propose and comment a case report of an 8 month old child who suffers from Bruton disease. Initial presentation was neutropenia, but genetic investigation has revealed a previously non-reported mutation in the BTK gene. The same mutation was found in the mother with low expression of BTK in monocytes and normal in B-cells suggesting a lineage specific extinction of BTK which has never been reported before.
authors.affiliation: Centre Hospitalier et Universitaire de Clermont-Ferrand, génétique médicale, F-63058 Clermont-Ferrand, France. alegrand@chu-clermontferrand.fr
authors.forename: Anne
authors.initials: A
authors.lastname: Debost-Legrand
authors.forename: Guillaume
authors.initials: G
authors.lastname: Legrand
authors.forename: Gaelle
authors.initials: G
authors.lastname: Moulillot
authors.forename: Christine
authors.initials: C
authors.lastname: Francannet
authors.forename: Bertrand
authors.initials: B
authors.lastname: Bocly
authors.forename: Ioannis
authors.initials: I
authors.lastname: Theodoroub
authors.forename: Catherine
authors.initials: C
authors.lastname: Paillard
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D004252:DNA Mutational Analysis; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D011505:Protein-Tyrosine Kinases / Q000235:genetics*
chemical_list: D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human
keywords: APC; Allophycocyanin; B-Cell Receptor; BCR; BTK; BTK gene; Bruton Tyrosine Kinase; Bruton tyrosine kinase; FITC-conjugated; Fluorescein Isothiocyanate-conjugated; Neutropenia; PBMC; PH; PI3K; PIP(3); Peripheral Blood Mononuclear Cell; Phosphatidylinositide 3-Kinases; Phosphatidylinositol (3,4,5)-Trisphosphate; Pleckstrin Homology; SH2; SH3; Scr Homology 3; Src Homology 2; TH; Tec Homology; X-Linked Agammaglobulinemia; X-linked agammaglobulinemia; XLA