Examples of hereditary immune deficiency diseases

Severe combined immune deficiency (SCID) is a
heterogeneous group of genetic disorders due
to various defects in both B cell and T differentiation.
X-linked agammaglobulinemia type Bruton
(McKusick 300300) was the first hereditary immune
deficiency described, in 1952 by Ogden
Bruton. The first developmental step of B cell
differentiation from pre-B to mature B cell is
blocked by deficiency of Bruton tyrosine kinase
due to mutations in the BTK gene on the X chromosome
(Xq22). Other forms involve later steps
of differentiation (variable immune deficiency)
or isolated Ig isotype (subclass) deficiencies.
Several T cell immune deficiency diseases exist.
The most important is the DiGeorge syndrome
(McKusick 188400), characterized by a broad
spectrum of highly variable manifestations. The
underlying defect involves the third and fourth
brachial arch derivatives during embryonic
development. A deletion in chromosome region
22q11 is found in most patients, usually as a de
novo event. Other disorders involve T cell activation
and function of one or both major subsets
of T cells, CD4 or CD8.