| Written | 2001-01 | Niels B Atkin |
| Department of Cancer Research, Mount Vernon Hospital, Northwood, Middlesex, UK |
| Identity |
| Other names | X-linked agammaglobulinemia (XLA) |
| Atlas_Id | 10023 |
| Genes implicated in | BTK |
| Inheritance | X-linked disorder occurring in males; frequency of XLA is about 0.3-0.6/105. |
| Clinics |
| Phenotype and clinics | immunological deficiency, first described in 1952, manifest from late infancy and typically resulting in frequent bacterial infections commencing in the second half of the first year of life: tonsils and lymph nodes are very small; marked decrease of serum immunoglobulins of all isotypes (maternal IgG gives some protection in early infancy) |
| Neoplastic risk | probably slight; in a 1963 paper, two patients with lymphoma were reported and reference was made to two adults with hypoglobulinemia who also had lymphomas; recent surveys of XLA patients do not reveal any cases of lymphoma; however, long-term vigilance needs to be maintained; at least seven cases of adenocarcinoma of the gastrointestinal tract in young adults with XLA have been reported; other malignancies have also been reported, but it is not clear whether they occur with an increased frequency |
| Treatment | vigorous antibiotic therapy and regular injections of immunoglobulin |
| Prognosis | good, on survival into early adulthood |
| Other findings |
| Note | absence of plasma cells in bone marrow and lymph nodes (the latter lack germinal centres) resulting in an almost complete lack of humoral immunity due to a failure of early B-lymphocyte development; normal myeloid and T-cell function: extremely deficient production of antibodies to all antigens |
| Genes involved and Proteins |
| Gene Name | BTK (Bruton's tyrosine kinase) |
| Location | Xq21.3-Xq22 |
| DNA/RNA | |
| Description | encoded in 19 exons spanning 37 kb |
| Protein | |
| Description | Btk is a 659 amino-acid cytoplasmic tyrosine kinase |
| Expression | is expressed at all except the terminally differentiated plasma cell stage of B-cell development |
| Function | it is a member of a small family of src-related hematopoietic kinases and, like them, has several interaction domains that allow it to bind to other components of signal-transduction pathways; unlike other src family members, Btk family members have a pleckstrin homology (PH) domain which is followed by a proline rich region that binds to the SH3 region of several src family members |
| Mutations | |
| Germinal | over 300 different mutations in Btk have been identified; only about 50% of patients with the clinical and laboratory findings of XLA have a family history of immunodeficiency; most of the remaining patients are the first manifestation of a new mutation in Btk; most mutations are single base-pair substitutions that result in premature stop codons, splice defects, or amino-acid substitutions. 5-10% of patients with XLA have gross alterations in the BTK gene (usually deletions) detectable by Southern-blot analysis; most amino-acid substitutions in Btk render the protein unstable and markedly reduced or absent |
| Bibliography |
| Agammaglobulinemia. |
| BRUTON OC |
| Pediatrics. 1952 ; 9 (6) : 722-728. |
| PMID 14929630 |
| X-linked agammaglobulinemia. |
| Conley ME, Rohrer J, Minegishi Y |
| Clinical reviews in allergy & immunology. 2000 ; 19 (2) : 183-204. |
| PMID 11107501 |
| The immunological deficiency diseases of man: consideration of some questions asked by these patients with an attempt at classification. |
| Good RA, Peterson RDA, Perey DY, Finstad J, Cooper MD |
| Birth Defects Original Article Series. 1968 ; 4 : 17-39. |
| Identification of Bruton's tyrosine kinase (Btk) gene mutations and characterization of the derived proteins in 35 X-linked agammaglobulinemia families: a nationwide study of Btk deficiency in Japan. |
| Hashimoto S, Tsukada S, Matsushita M, Miyawaki T, Niida Y, Yachie A, Kobayashi S, Iwata T, Hayakawa H, Matsuoka H, Tsuge I, Yamadori T, Kunikata T, Arai S, Yoshizaki K, Taniguchi N, Kishimoto T |
| Blood. 1996 ; 88 (2) : 561-573. |
| PMID 8695804 |
| Occurrence of leukemia and lymphoma in patients with agammaglobulinemia. |
| PAGE AR, HANSEN AE, GOOD RA |
| Blood. 1963 ; 21 : 197-206. |
| PMID 13941046 |
| Activation of BTK by a phosphorylation mechanism initiated by SRC family kinases. |
| Rawlings DJ, Scharenberg AM, Park H, Wahl MI, Lin S, Kato RM, Fluckiger AC, Witte ON, Kinet JP |
| Science (New York, N.Y.). 1996 ; 271 (5250) : 822-825. |
| PMID 8629002 |
| Symposium on gene abnormalities in medical diseases. 1. Immunological diseases: Bruton's agammaglobulinemia. |
| Tsukada S |
| Internal medicine (Tokyo, Japan). 1997 ; 36 (2) : 148-150. |
| PMID 9099606 |
| Citation |
| This paper should be referenced as such : |
| Atkin, NB |
| Bruton's agammaglobulinemia |
| Atlas Genet Cytogenet Oncol Haematol. 2001;5(2):139-140. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Tumors/BrutonAgammaID10023.html |
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Fri Jun 30 11:24:11 CEST 2017 |
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