X-linked Agammaglobulinemia - Genetics

Genetics

The Btk enzyme plays an essential role in the maturation of B cells in the bone marrow, and when mutated, immature pre-B lymphocytes are unable to develop into mature B cells that leave the bone marrow into the blood stream. The disorder is X-linked (it is on the X chromosome), and is almost entirely limited to the sons of asymptomatic female carriers . This is because males have only one copy of the X chromosome, while females have two copies; one normal copy of an X chromosome can compensate for mutations in the other X chromosome, so they are less likely to be symptomatic. Females carriers have a 50% chance of giving birth to a male child with XLA.

An XLA patient will pass on the gene, and all of his daughters will be XLA carriers, meaning that any male grandchildren from an XLA patient's daughters have a 50% chance of inheriting XLA. A female XLA patient can arise only as the child of an XLA patient and a carrier mother. XLA can also rarely result from a spontaneous mutation in the fetus of a non-carrier mother.