Agammaglobulinemias, including the following six diseases:
X-linked agammaglobulinemia (Bruton's agammaglobulinemia, XLA);
IgM heavy chain gene deletions;
Ig-alpha defect;
Autosomal recessive agammaglobulinaemia;
B cell-linker protein (BLNK) deficiency;
Leucine-rich repeat-containing 8

There are three major categories of antibody deficiencies: (a) defects in early B cell development, (b) hyper-IgM syndromes (also called class switch recombination defects), and (c) common variable immunodeficiency (CVID). Category (a) consists of agammaglobulinaemias. Defects in early B cell development are characterized by the onset of recurrent bacterial infections in the first 5 years of life, profound hypogammaglobulinemia, markedly reduced or absent B cells in the peripheral circulation, and (in the bone marrow) a severe block in B cell differentiation before the production of surface immunoglobulin-positive B cells. Mutations in Btk, the gene responsible for X-linked agammaglobulinemia (XLA), account for approximately 85% of affected patients. Approximately half of the remaining patients have mutations in genes encoding components of the pre-B cell receptor (pre-BCR) or BCR, including mu heavy chain (IGHM); the signal transduction molecules Ig-alpha (CD79A) and Ig-beta (CD79B); and lambda 5 (IGLL1), which forms the surrogate light chain with Vpre-B. A small number of patients with defects in BLNK, a scaffold protein that assembles signal transduction molecules activated by cross-linking of the BCR, have been reported.

Primary immunodeficiency

Btk [HSA:695] [KO:K07370]
CD79a [HSA:973] [KO:K06506]
mu (IGHM)
lamda 5(CD179B) [HSA:3543] [KO:K06554]
BLNK [HSA:29760] [KO:K07371]
LRRC8 [HSA:56262 23507 84230 55144 80131]
CD79B [HSA:974] [KO:K06507]

PMID:19302039 (description, gene)

Conley ME, Dobbs AK, Farmer DM, Kilic S, Paris K, Grigoriadou S, Coustan-Smith E, Howard V, Campana D

Primary B cell immunodeficiencies: comparisons and contrasts.

Annu Rev Immunol 27:199-227 (2009)

PMID:17162365 (gene)

Kumar A, Teuber SS, Gershwin ME.

Current perspectives on primary immunodeficiency diseases.

Clin Dev Immunol 13:223-59 (2006)

PMID:9737224 (gene)

Ten RM.

Primary immunodeficiencies.

Mayo Clin Proc 73:865-72 (1998)

PMID:15096561 (gene)

Lim MS, Elenitoba-Johnson KS.

The molecular pathology of primary immunodeficiencies.

J Mol Diagn 6:59-83 (2004)

PMID:18424339 (gene)

Morra M, Geigenmuller U, Curran J, Rainville IR, Brennan T, Curtis J, Reichert V, Hovhannisyan H, Majzoub J, Miller DT.

Genetic diagnosis of primary immune deficiencies.

Immunol Allergy Clin North Am 28:387-412, x (2008)

PMID:17952897 (gene)

Geha RS, Notarangelo LD, Casanova JL, Chapel H, Conley ME, Fischer A, Hammarstrom L, Nonoyama S, Ochs HD, Puck JM, Roifman C, Seger R, Wedgwood J.

Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee.

J Allergy Clin Immunol 120:776-94 (2007)