title: Identification of a Btk mutation in a dysgammaglobulinemic patient with reduced B cells: XLA diagnosis or not?
abstract: The identification of a Btk mutation in a male patient with <2% CD19(+) B cells warrants making the diagnosis of X-linked Agammaglobulinemia (XLA). Herein we report the case of a 31 year-old male with a gradual decline of peripheral B lymphocytes and low IgA and IgM but normal IgG levels. His clinical history revealed recurrent respiratory and skin infections, sclerosing cholangitis and chronic obstructive pancreatitis. Molecular studies revealed a novel aminoacidic substitution in Btk protein (T316A). His mother, maternal aunts and a maternal female cousin were heterozygotes for the same Btk mutation and were variably affected with pulmonary emphysema. This is a puzzling case where the patient's clinical history and laboratory findings divorce molecular genetics. Either this case confirms the variable expressivity of XLA disease or the T316A change in Btk SH2 domain is a novel non-pathogenic mutation and another unknown gene alteration is responsible for the disease.
authors: Department of Pediatrics, University of Rome Tor Vergata, Rome, Italy.
authors: Simona
authors: S
authors: Graziani
authors: Gigliola
authors: G
authors: Di Matteo
authors: Luigi
authors: L
authors: Benini
authors: Silvia
authors: S
authors: Di Cesare
authors: Maria
authors: M
authors: Chiriaco
authors: Loredana
authors: L
authors: Chini
authors: Marco
authors: M
authors: Chianca
authors: Fosca
authors: F
authors: De Iorio
authors: Maria
authors: M
authors: La Rocca
authors: Roberta
authors: R
authors: Iannini
authors: Stefania
authors: S
authors: Corrente
authors: Paolo
authors: P
authors: Rossi
authors: Viviana
authors: V
authors: Moschese
mesh_terms: D000328:Adult; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology; D019943:Amino Acid Substitution; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human