Detection of a novel mutation in the SRC homology domain 2 (SH2) of Bruton`s tyrosine kinase and direct female carrier evaluation in a family with x-linked agammaglobulinemia
- Univ. of Wuerzburg (Germany)
X-linked agammaglobulinemia (XLA) is an inherited immunodeficiency disease with a block in differentiation from pre-B to B cells resulting in a selective defect in the humoral immune response. Affected males have very low concentrations of serum immunoglobulins leading predominantly to recurrent bacterial infections beginning at age 6 to 18 months. The gene responsible for XLA was identified recently to encode a cytoplasmatic tyrosine kinase (Bruton`s tyrosine kinase, BTK). We have analyzed the BTK gene in a large family in which two brothers presented with the severe phenotype of XLA. Genomic DNA of affected boys and from healthy relatives was amplified by PCR with primers specific for the putative promoter region and for all 19 exons, including flanking intron boundaries, and subsequently screened for mutations using single strand conformation polymorphism (SSCP) analysis. Altered single strand band patterns were found using primers specific for exon 10, 15, and 18. Direct cycle-sequencing of these BTK segments detected two known polymorphisms in intron 14 and in exon 18. Sequencing of exon 10 from two boys with XLA demonstrated a novel point mutation in the SH2 domain of BTK. Direct identification of healthy female carriers in three generations was performed by amplification mutagenesis using PCR with a modified first primer. This method can easily be applied also to prenatal diagnosis. 25 refs., 3 figs.
- OSTI ID:
- 441204
- Journal Information:
- American Journal of Medical Genetics, Journal Name: American Journal of Medical Genetics Journal Issue: 1 Vol. 63; ISSN 0148-7299; ISSN AJMGDA
- Country of Publication:
- United States
- Language:
- English
Similar Records
Genomic organization of Bruton`s tyrosine kinase
Four mutations in SH2 and SH3 domains of Bruton`s tyrosine kinase (BTK) resulting in classic X-linked agammaglobulinemia (XLA)
Related Subjects
BASIC STUDIES
AMINO ACIDS
BIOLOGICAL MARKERS
DETECTION
DNA SEQUENCING
EXONS
GENE MUTATIONS
GENETIC MAPPING
GENETICS
HEREDITARY DISEASES
HUMAN X CHROMOSOME
IMMUNE SYSTEM DISEASES
IMMUNOGLOBULINS
PATIENTS
PHENOTYPE
PHOSPHOTRANSFERASES
POLYMERASE CHAIN REACTION
STRUCTURE-ACTIVITY RELATIONSHIPS
TYROSINE