title: Genotype/phenotype correlations in X-linked agammaglobulinemia.
abstract: No clear genotype/phenotype correlations have been established in patients with X-linked agammaglobulinemia (XLA). To determine if the specific mutation in Btk might be one of the factors that influences the severity of disease or if polymorphic variants in Tec, a cytoplasmic tyrosine kinase that might substitute for Btk, could contribute to the clinical phenotype, we examined the age at diagnosis, the percentage of peripheral blood B cells and the plasma IgM in a large group of patients with XLA. The results demonstrated that polymorphic variants in Tec were not correlated with phenotypic markers; however, the specific mutation in Btk did influence disease severity. Mutations that conceivably allow the production of some Btk, amino acid substitutions or splice defects that occur at conserved but not invariant sites in the splice consensus sequence were associated with older age at diagnosis, a higher percentage of B cells in the peripheral circulation and higher concentrations of plasma IgM.
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, USA.
authors.forename: Arnon
authors.initials: A
authors.lastname: Broides
authors.forename: Wenjian
authors.initials: W
authors.lastname: Yang
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Conley
mesh_terms: D000293:Adolescent; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000201:enzymology / Q000235:genetics* / Q000276:immunology*; D017668:Age of Onset; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005838:Genotype; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D007223:Infant; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics
chemical_list: D007075:Immunoglobulin M; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human