Identification of a Btk mutation in a dysgammaglobulinemic patient with reduced B cells: XLA diagnosis or not?
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.
Graziani
Simona
S
Department of Pediatrics, University of Rome Tor Vergata, Rome, Italy.
Di Matteo
Gigliola
G
Benini
Luigi
L
Di Cesare
Silvia
S
Chiriaco
Maria
M
Chini
Loredana
L
Chianca
Marco
M
De Iorio
Fosca
F
La Rocca
Maria
M
Iannini
Roberta
R
Corrente
Stefania
S
Rossi
Paolo
P
Moschese
Viviana
V
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
D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human