It majority of BTK mutations result in

It is important to confirm XLA diagnosis as it will help rule
out other treatable causes of the immunodeficiency and early diagnosis is urged
in cases of XLA, also a definitive diagnosis will have implications for the patient’s
family members and offer some prognostic information. In order to definitely
confirm that it is indeed XLA, the patients can undergo molecular testing by sequencing
of the BtK gene, this is the gold standard for definitively identifying
mutations and confirming a diagnosis. However, it is an expensive and labour
intensive procedure. Therefore flow cytometry should be used as a screening test,
especially in male patients such a Jack who have less than 2% B- lymphocytes .The
majority of BTK mutations result in deficient BTK expression, reflecting a
reduction in BTK mRNA or an instability of the produced protein. Flow cytometry
screening assay will detected the expression of Bruton tyrosine kinase protein in
monocytes, platelets and circulating B cells, the results are then compared to
that of a normal donor Fig.2. This test will either report
it as being present, absent, partial deficiency or mosaic (carrier), the degree
of Btk deficiency varies from person to person. However , flow cytometry is
just a preliminary screening test as 20% to 30 % of patients who have a
mutation within the Btk gene may have normal protein expression ; this is largely
related to the position of the mutation in the gene and the antibody used for
flow cytometry analysis .In order to confirm the presence of a Btk mutation, it
is advised to include both flow cytometry and gene sequencing this is
especially true if flow cytometry has shown an absence/ deficiency in Btk
protein (Kanegane, et al., 2001). Genetic analysis such
as whole exome sequencing are used to identify the mutation which will reveal
mutations that can be classified as either severe or less severe. Frameshift,
missense and nonsense mutations that result into protein truncation are
considered severe (Rawat, et al., 2016) (Chen, et al.,
2016).Btk
gene testing is most effective if familial Btk mutation is already known,
therefore it is necessary the patient’s (jack ) deeper family history
investigation of the disease is carried out .