X-linked Agammaglobulinemia (also known as Bruton Agammaglobulinemia) is caused by a mutation in the gene coding for Bruton tyrosine kinase (BTK). From the research you did after reading the case, what is the role of BTK and how are B-lymphocytes affected?
In X-linked Agammaglobulinemia, there is a failure of maturation of B cell precursor to mature B cells and plasma cells. Hence, these patients lack all immunoglobulins as well as peripheral blood B cells. They however, have B cell precursors. The defect in B cell maturation is due to mutation in the Burton’s tyrosine kinase or BTK. Mostly, boys are affected as this is an X linked disorder.
The BTK gene encodes a cytoplasmic nonreceptor protein tyrosine kinase belonging to Tec kinase family. This Tec kinase has a N-terminal PH domain, proline rich Tec homology domain, SH3 and SH2 domains and a SH1 kinase domain. The activation of Tec kinases is one of first step in antigen-receptor signaling. The PH domain is required for BTK membrane localization. The Tec domain has a BTK motif that is required for binding to Zinc ions. The SH3 and SH2 domains contain autophosphorylation sites tyrosine 223. The SH1 kinase domain has phosphorylation site 551.
BTK is involved in antigen induced B cell receptor signaling. In the first step of B cell receptor (BCR) activation, there is clustering of Igα and Igβ (CD79a and CD79b) molecules. This is followed by phosphorylation of immunoreceptor tyrosine [kinase] activation motifs (ITAMs) at the cytoplasmic domain, mediated by Lyn kinases. Lyn will also phosphorylate BTK and CD19. This leads to PI3K activation, causing increase in levels of phosphatidylinositol 4,5-triphosphate (PIP3) on the cytoplasmic side of plasma membrane. Then, spleen tyrosine kinase (SYK) binds to ITAM motifs, and activates them. SYK phosphorylates tyrosine residues in B cell linker scaffold protein or BLNK.
In order to stimulate antigen receptors, BTK has to interact with PIP3 via its PH domain.SH2 domain binds to BLNK. Phosphorylation of tyrosine 551 leads to autophosphorylation of tyrosine 223, causing BCR stimulation and activation of BTK. BTK then phosphorylates phospholipase C gamma 2. This leads to break down of PIP2 into the inositol 1,4,5-triphosphate and diacylglycerol. These secondary messengers cause increase in intracellular calcium. BTK also activates toll like receptor signaling. If BTK is inactive, BCR signaling cannot convert late transitional B cells into mature peripheral B cells. BTK can also form complexes with class II MHC molecules, MyD88 and CD40. It may also be involved in aggregation of platelets.
X-linked Agammaglobulinemia (also known as Bruton Agammaglobulinemia) is caused by a mutation in the gene coding...
How can a dominant lethal mutation (such as that for Rest Syndrome) be transmitted to future generations? - Rett syndrome caused by mutations in the gene that encodes MeCP2 and is X-linked
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ignore my markings. If its a X-linked recessive mutation, i presume the mutated X is coming from the father. So then, why is the Parental Generation male unaffected??? points) Consider the below pedigree for hemophilia, caused by a completely penetrant, X-1 .cessive mutation. tx ta Xaxt xt Xtxt xt ya x X xtya x Y xty > +9 (a) What is the probability that II:2 is a carrier?
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