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X-Linked Agammaglobulinemia

Synonyms: Bruton's Agammaglobulinemia, XLA

, MD and , RN, MSN.

Author Information
, MD
Department of Immunology
St Jude Children's Research Hospital
Memphis, Tennessee
Department of Immunology
St Jude Children's Research Hospital
Memphis, Tennessee

Initial Posting: ; Last Update: November 17, 2011.


Clinical characteristics.

X-linked agammaglobulinemia (XLA) is characterized by recurrent bacterial infections in affected males in the first two years of life. Recurrent otitis is the most common infection prior to diagnosis. Conjunctivitis, sinopulmonary infections, diarrhea, and skin infections are also frequently seen. Approximately 60% of individuals with XLA are recognized as having immunodeficiency when they develop a severe, life-threatening infection such as pneumonia, empyema, meningitis, sepsis, cellulitis, or septic arthritis. S pneumoniae and H influenzae are the most common organisms found prior to diagnosis and may continue to cause sinusitis and otitis after diagnosis and the initiation of gammaglobulin therapy. The prognosis for individuals with XLA has improved markedly in the last 25 years as a result of earlier diagnosis, the development of preparations of gammaglobulin that allow normal concentrations of serum IgG to be achieved, and more liberal use of antibiotics.


The diagnosis of XLA is suspected in males with early-onset bacterial infections, marked reduction in all classes of serum immunoglobulins, and absent B cells (CD19+ cells); the decrease in the number of B cells is the most consistent and distinctive feature. The diagnosis is established or confirmed only in those individuals who have a mutation in BTK or who have a maternal uncle or cousin with absent B cells. Approximately 90% of males with early-onset infections, hypogammaglobulinemia, and absent B cells have mutations in BTK. The remaining 10% of patients have mutations in other genes that cause a failure in B cell development or have unknown causes of agammaglobulinemia. Molecular genetic testing of BTK is the most reliable way to identify female carriers of XLA.


Treatment of manifestations: The mainstay of treatment is gammaglobulin replacement by weekly subcutaneous injection or intravenous infusion every two to four weeks to prevent bacterial infections; some centers use chronic prophylactic antibiotics to prevent infections.

Prevention of secondary complications: The most common secondary complications of XLA are chronic sinusitis, chronic lung disease, inflammatory bowel disease, and enteroviral infection. Aggressive use of antibiotics can decrease the incidence of chronic sinusitis and lung disease; diagnosis and treatment of bowel infections may decrease the risk of inflammatory bowel disease. Inactivated polio vaccine rather than live oral polio vaccine should be given to patients with XLA and their family contacts.

Agents/circumstances to avoid: Live viral vaccines, particularly oral polio vaccine.

Evaluation of relatives at risk: Molecular genetic testing of at-risk male relatives as soon after birth as possible ensures that gammaglobulin replacement therapy is initiated as soon as possible in affected individuals.

Genetic counseling.

XLA is inherited in an X-linked manner. Mothers who have an affected son and one other affected relative in the maternal line (e.g., brother, uncle, nephew) are obligate carriers. Fifty percent of males have no family history of XLA. If an affected male has no family history of XLA, two possibilities exist: the mother is not a carrier and the affected male has a de novo disease-causing mutation (~15%-20% of cases) or the mother is a carrier of a disease-causing mutation (~80%-85% of cases). The risk to the sibs of a male proband depends on the mother's carrier status. All daughters of a male proband will inherit the mutant BTK allele and will be carriers for XLA. Carrier testing for at-risk female relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutation in the family is known.


The following diagnostic criteria for X-linked agammoglobulinemia were published in 1999. There is an ongoing effort to update the diagnostic criteria (for all inherited immunodeficiencies) but no updates have been published [Conley et al 1999].

Definitive diagnosis. Male with less than 2% CD19+ B cells and at least one of the following:

  • Mutation in BTK
  • Absent Btk mRNA on northern blot analysis of neutrophils or monocytes
  • Absent Btk protein in monocytes or platelets
  • Maternal cousins, uncles, or nephews with less than 2% CD19+ B cells

Probable diagnosis. Male with less than 2% CD19+ B cells and the following:

  • Onset of recurrent bacterial infections in the first five years of life
  • Serum IgG, IgM, and IgA more than 2 SD below normal for age
  • Absent isohemagglutinins and/or poor response to vaccines
  • Exclusion of other causes of hypogammaglobulinemia

Possible diagnosis. Male with less than 2% CD19+ B cells in whom other causes of hypogammaglobulinemia have been excluded, who has at least one of the following:

  • Onset of recurrent bacterial infections in the first five years of life
  • Serum IgG, IgM, and IgA more than 2 SD below normal for age
  • Absent isohemagglutinins

Spectrum of disease

Approximately 10%-15% of individuals with XLA have higher concentrations of serum immunoglobulin than expected or are not recognized to have immunodeficiency until after age five years.

Clinical Diagnosis

The diagnosis of X-linked agammaglobulinemia (XLA) is considered in individuals with any of the following:

  • Recurrent otitis, pneumonitis, sinusitis, and conjunctivitis starting before age five years
  • A severe life-threatening bacterial infection such as sepsis, meningitis, cellulitis, or empyema
  • Paucity of lymphoid tissue (small tonsils and lymph nodes on physical examination)
  • Family history of immunodeficiency consistent with X-linked inheritance


Testing of Immune Function

Affected individuals. Specific blood tests and findings that help confirm the diagnosis of XLA:

  • Concentration of serum immunoglobulins [Lederman & Winkelstein 1985, Conley et al 2005]
    • The serum IgG concentration is typically less than 200 mg/dL. Most but not all individuals with XLA do have some measurable serum IgG, usually between 100 and 200 mg/dL, and approximately 10% of individuals have serum concentration of IgG greater than 200 mg/dL.
    • The serum concentrations of IgM and IgA are typically less than 20 mg/dL. Particular attention should be given to serum IgM concentration. Although decreased serum concentration of IgG and IgA can be seen in children with a constitutional delay in immunoglobulin production, low serum IgM concentration is almost always associated with immunodeficiency.
  • Antibody titers to vaccine antigens. Individuals with XLA fail to make antibodies to vaccine antigens like tetanus, H influenzae, or S pneumoniae.
  • Lymphocyte cell surface markers. The most consistent feature in XLA is markedly reduced numbers of B lymphocytes (CD 19+ cells) in the peripheral circulation (<1%) [Conley 1985, Nonoyama et al 1998]
  • Severe neutropenia is seen in approximately 10%-25% of individuals at the time of diagnosis, usually in association with pseudomonas or staphylococcal sepsis [Conley & Howard 2002]. Neutropenia is generally not seen after the initiation of gammaglobulin therapy.

The immune system is otherwise normal.

Female carriers. Tests of immune function are normal.

BTK Protein Testing

Because most mutations in BTK result in the absence of the BTK protein in monocytes, some research laboratories have developed techniques that allow the detection of BTK protein in monocytes by immunofluorescence or western blot [Futatani et al 1998, Gaspar et al 1998]. This can help confirm the diagnosis of XLA when molecular genetic testing is not available or is unsuccessful at detecting a mutation.

Molecular Genetic Testing

Gene. BTK is the only gene in which mutations are known to cause XLA.

Clinical testing

  • Mutation scanning/sequence analysis. These methods detect approximately 90% of mutations in BTK, including the approximately 70% that are single base-pair changes resulting in amino acid substitutions, premature stop codons, or splice defects and the 22% that are small insertions, deletions, or small rearrangements with deletion of some nucleotides and insertion of others.
  • Duplication/deletion analysis. Duplication/deletion testing detects the 8% of mutations that are partial- or whole-gene deletions, duplications, inversions, or insertions.

Table 1.

Summary of Molecular Genetic Testing Used in X-Linked Agammaglobulinemia (XLA)

GeneTest MethodMutations DetectedMutation Detection Frequency by Test Method 1
MalesHeterozygous Females
BTKSequence analysis / mutation scanning 2Sequence variants 3100% 4, 592% 6
Deletion/ duplication analysis 7Deletion / duplication of one or more exons or the whole gene 8% 88%

The ability of the test method used to detect a mutation that is present in the indicated gene


Sequence analysis and mutation scanning of the entire gene can have similar mutation detection frequencies; however, mutation detection rates for mutation scanning may vary considerably between laboratories depending on the specific protocol used.


Examples of mutations detected by sequence analysis may include small intragenic deletions/insertions and missense, nonsense, and splice site mutations.


Lack of amplification by PCRs prior to sequence analysis can suggest a putative deletion of one or more exons or the entire X-linked gene in a male; confirmation may require additional testing by deletion/duplication analysis. See footnote 7.


Includes the mutation detection frequency using deletion/duplication analysis.


Sequence analysis of genomic DNA cannot detect deletion of one or more exons or the entire X-linked gene in a heterozygous female.


Testing that identifies deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; a variety of methods including quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), or targeted chromosomal microarray analysis (gene/segment-specific) may be used. A full chromosomal microarray analysis that detects deletions/duplications across the genome may also include this gene/segment.


Males initially suspected on sequence analysis of having a deletion in whom the deletion is subsequently confirmed by deletion/duplication analysis

Interpretation of test results. For issues to consider in interpretation of sequence analysis results, click here.

Testing Strategy

To confirm/establish the diagnosis in a proband. When the diagnosis of XLA is suspected because a child has had recurrent, persistent, or severe infections:

  • Serum immunoglobulins and titers to vaccine antigens should be measured.
  • If these are abnormal or the index of suspicion is high, the percentage of CD19+ B cells in the blood should be determined.
  • Molecular genetic testing using sequence analysis/mutation scanning first, and then if a mutation is not identified, by deletion/duplication analysis, should be performed to confirm/establish the diagnosis.

If a newborn or infant is being evaluated because of a positive family history of XLA:

  • Serum immunoglobulins will not be helpful because maternal IgG crosses the placenta.
  • The percentage of B cells should be analyzed as a first step.
  • If the percentage of B cells is low, it is reasonable to pursue molecular genetic testing to determine if the at-risk family member has the family-specific mutation.

Carrier testing for at-risk relatives requires prior identification of the disease-causing mutation in the family.

Note: (1) Carriers are heterozygotes for this X-linked disorder and usually do not develop clinical findings related to the disorder. (2) Identification of female carriers requires either (a) prior identification of the disease-causing mutation in the family or, (b) if an affected male is not available for testing, molecular genetic testing first by sequence analysis, and then, if no mutation is identified, by methods to detect gross structural abnormalities.

Analysis of X-chromosome inactivation patterns has been helpful in assessing carrier risk of at-risk female relatives in the past. However, given the high sensitivity and specificity of clinical molecular genetic testing in current use, this approach is rarely used.

Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies require prior identification of the disease-causing mutation in the family.

Clinical Characteristics

Clinical Description

Individuals with X-linked agammaglobulinemia (XLA) are usually well for the first few months of life because they are protected by transplacentally acquired maternal immunoglobulin. Typically, affected males develop recurrent bacterial infections in the first two years of life and are recognized as having immunodeficiency before age five years [Conley & Howard 2002, Plebani et al 2002]. The most common infecting organisms include H influenzae and S pneumoniae. Approximately 10% of individuals with mutations in BTK are not recognized as having immunodeficiency until after age ten years and some not until adulthood [Howard et al 2006, Conley et al 2008]. Some patients have higher serum immunoglobulin concentrations than expected, but all have very low numbers of B cells.

Recurrent otitis is the most common infection prior to diagnosis. Conjunctivitis, sinopulmonary infections, diarrhea, and skin infections are also frequently seen. Approximately 60% of individuals with XLA are recognized as having immunodeficiency when they develop a severe, life-threatening infection such as pneumonia, empyema, meningitis, sepsis, cellulitis, or septic arthritis. S pneumoniae and H influenzae are the most commonly seen organisms prior to diagnosis and they may continue to cause sinusitis and otitis after diagnosis and the initiation of gammaglobulin therapy [Lederman & Winkelstein 1985, Conley et al 2005].

Individuals with XLA are not unusually vulnerable to most viral infections; however, they are susceptible to severe and chronic enteroviral infections [Wilfert et al 1977]. In the past, 5%-10% of individuals with XLA developed vaccine-associated polio after vaccination with the live attenuated oral polio vaccine. Since the mid-1980s, when intravenous gammaglobulin became available, the incidence of chronic enteroviral infection has markedly decreased in individuals with XLA. However, some patients still develop enteroviral encephalitis and some have neurologic deterioration of unknown etiology [Misbah et al 1992, Ziegner et al 2002].

Like all individuals with antibody deficiencies, persons with XLA are unusually susceptible to giardia infection. They may also develop problems with persistent mycoplasma infections. Infections with unusual organisms, like Flexispira or Helicobacter cinaedi, may also be troublesome [Cuccherini et al 2000, Simons et al 2004].

The prognosis for individuals with XLA has improved markedly in the last 25 years [Howard et al 2006] as a result of earlier diagnosis, more liberal use of antibiotics, and the development of preparations of gammaglobulin that allow normal concentrations of serum IgG to be achieved. Most individuals lead a normal life. However, approximately 10% of individuals develop significant infections despite appropriate therapy and many have chronic pulmonary changes [Quartier et al 1999].

Heterozygotes. One female with XLA has been reported. The father of this child had XLA and analysis of her buccal epithelium and peripheral blood demonstrated exclusive use of the paternally derived X chromosome as the active X [Takada et al 2004].

Genotype-Phenotype Correlations

No strong correlation is observed between the specific mutation in BTK and the severity of disease; however, individuals who have amino acid substitutions or splice defects that occur at sites that are conserved, but not invariant, tend to be older at the time of diagnosis, and they have higher serum concentrations of IgM and slightly more B cells in the peripheral circulation [López-Granados et al 2005, Broides et al 2006].


Bruton called the disorder that he first described in 1952 “agammaglobulinemia.” The X-linked pattern of inheritance was noted shortly after that time. In the 50s, 60s, and 70s, the disorder was sometimes called congenital agammaglobulinemia, familial hypogammaglobulinemia or infantile agammaglobulinemia, or simply agammaglobulinemia.


Prevalence is approximately three to six per million males in all racial and ethnic groups.

Differential Diagnosis

Approximately 90% of males who are presumed to have X-linked agammaglobulinemia (XLA) based on early onset of infections, severe hypogammaglobulinemia, and markedly reduced numbers of B cells have detectable mutations in BTK [Conley et al 1998].

The majority of females with an XLA-like phenotype and males with an XLA phenotype who do not have an identifiable BTK mutation are likely to have defects in other genes required for normal B-cell development including µ heavy chain, Igα, Igβ, λ5, and BLNK. These autosomal recessive forms of agammaglobulinemia are very rare.

  • Thirty individuals with 21 different mutations in µ heavy chain have been reported [López-Granados et al 2002, Ferrari et al 2007b, van Zelm et al 2008]. These individuals tend to come to medical attention at an earlier age and are more likely to have life-threatening infections than individuals with XLA, but clinical overlap is considerable.
  • Defects in Igα, Igβ λ5, or BLNK have been reported in fewer than five individuals for each disorder. Individuals with any of these four genetic defects cannot be distinguished by routine clinical or laboratory tests from individuals with XLA [Conley et al 2005, Dobbs et al 2007, Ferrari et al 2007a].

These disorders should be considered in females who have an XLA-like phenotype or in males who were presumed to have XLA but who do not have mutations in BTK. Families with a known history of consanguinity are more likely to have rare autosomal recessive forms of agammaglobulinemia.

The underlying defect remains unknown in approximately 5% of individuals with congenital agammaglobulinemia and absent B cells.

Low concentrations of serum immunoglobulins can be seen in a variety of conditions, including the following X-linked disorders:

However, individuals with these disorders usually have relatively normal or elevated numbers of B cells.


Evaluations Following Initial Diagnosis

A patient with XLA should receive specialty care at a center with expertise in this disorder.

To establish the extent of disease and needs of an individual diagnosed with X-linked agammaglobulinemia (XLA), the following evaluations are recommended:

  • A complete blood count with differential
  • Chemistries that include renal and liver function tests, total protein, albumin, and CRP
  • Quantitative serum immunoglobulins and titers to vaccine antigens
  • Base line chest and sinus x-rays
  • If the patient is able to cooperate, base line pulmonary function tests

Treatment of Manifestations

If individuals develop acute infections, they should be treated with a course of antibiotics that is at least twice as long as that used in otherwise healthy individuals.

Prevention of Primary Manifestations

Bacterial Infections

Gammaglobulin is the mainstay of treatment for individuals with XLA. Most individuals in the United States are given approximately 400 mg/kg of gammaglobulin every four weeks. In the past, the majority of individuals received their gammaglobulin by intravenous infusion every two to four weeks. In the last few years, an increasing proportion of individuals have been receiving their gammaglobulin by weekly subcutaneous injections. Both routes provide good therapeutic concentrations of serum IgG. The choice of route may depend on factors related to the convenience of the physician and patient [Berger 2004].

A variety of brands of gammaglobulin are available; none has proven to be superior to others as measured by efficacy or side effects. Occasionally, individuals with XLA have a reaction to gammaglobulin, consisting of headaches, chills, backache, or nausea. These reactions are more likely to occur when the individual has an intercurrent viral infection or when the brand of gammaglobulin has been changed.

Chronic prophylactic antibiotics are used in some centers for prevention of bacterial infections.

Prevention of Secondary Complications

Children with XLA should be given inactivated polio vaccine (IPV) rather than oral polio vaccine.

The siblings of children with XLA should also be given IPV rather than oral polio vaccine (in order to avoid infecting their affected sib with live virus).


At least once a year:

  • A complete blood count with differential, chemistries, and quantitative serum immunoglobulins
  • Chest x-rays or CTs and sinus films
    Note: Chronic lung disease can develop in the absence of an acute pulmonary infection [Quartier et al 1999].

If the patient is stable, the serum IgG does not need to be evaluated with every infusion of gammaglobulin.

Agents/Circumstances to Avoid

Live viral vaccines, particularly oral polio vaccine, should be avoided in individuals with XLA.

Evaluation of Relatives at Risk

It is appropriate to evaluate at-risk male relatives as soon after birth as possible by molecular genetic testing for the known family-specific BTK mutation or by analyzing the percentage of B cells in the peripheral circulation, so that gammaglobulin replacement therapy can be initiated as soon as possible and so that administration of live viral vaccines can be avoided.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Pregnancy Management

No special precautions need to be taken at the time of delivery of an infant known to have XLA.

Therapies Under Investigation

Research studies exploring gene therapy for XLA have been conducted in mice [Kerns et al 2010, Ng et al 2010], but it is not clear when this type of treatment may be available for humans.

Search for access to information on clinical studies for a wide range of diseases and conditions.


Affected individuals are encouraged to lead a normal, active life including participation in sports.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

X-linked agammaglobulinemia is inherited in an X-linked manner.

Risk to Family Members

Parents of a male proband

Sibs of a male proband

  • The risk to the sibs depends on the carrier status of the mother.
  • If the mother is a carrier, there is a 50% chance of transmitting the BTK mutation in each pregnancy:
    • Male sibs who inherit the mutation will be affected; female sibs who inherit the mutation will be carriers.
    • Females carrying a BTK mutation are asymptomatic.
  • If the proband is the only affected individual in the family and if his mother's carrier status is unknown, she has an approximately 80% chance of being a carrier [Conley et al 1998]. Thus, male sibs have a 40% chance of having XLA and female sibs have a 40% chance of being carriers.
  • Germline mosaicism has been observed. Thus, if an affected male represents a single case in a family and if his mother has no evidence of her son's BTK disease-causing mutation in DNA extracted from her leukocytes, the male sibs are still at increased risk (<5%) of being affected.

Offspring of a male proband

  • All daughters of a male proband will inherit the mutant BTK allele and will be carriers for XLA. Females carrying a BTK mutation are asymptomatic.
  • The sons of a male proband will not inherit the mutant allele, have XLA, or pass it on to their offspring.

Other family members of a male proband. The proband's maternal aunts and their offspring may be at risk of being carriers or being affected (depending on their gender, family relationship, and the carrier status of the proband's mother). Linkage analysis has shown that the maternal grandfather is the source of a de novo mutation in the majority of males who have no family history of XLA and that the maternal grandmothers are carriers less than 20% of the time [Conley et al 1998]. Therefore, the risk that the maternal aunt of a boy with no family history of XLA is a carrier is less than 10%.

Carrier Detection

Carrier testing of at-risk female relatives is possible if the disease-causing mutation in the family is known.

When the BTK mutation in the proband has not been identified, linkage analysis can be used to provide carrier detection in families with an unequivocal diagnosis of XLA in multiple generations.

Related Genetic Counseling Issues

See Management, Evaluation of Relatives at Risk for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.

Family planning

  • The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing

Prenatal testing is possible for pregnancies of women who are carriers. The usual procedure is to determine fetal sex by performing chromosome analysis on fetal cells obtained by chorionic villus sampling (usually performed at ~10-12 weeks' gestation) or by amniocentesis (usually performed at ~15-18 weeks' gestation). If the karyotype is 46,XY and if the disease-causing mutation has been identified in a family member, DNA from fetal cells can be analyzed for the known disease-causing mutation.

Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.

Prenatal testing for conditions which (like X-linked agammaglobulinemia) do not affect intellect and have some treatment available is not commonly requested. Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. Although decisions about prenatal testing are the choice of the parents, discussion of these issues is appropriate.

Preimplantation genetic diagnosis (PGD) may be an option for some families in which the disease-causing mutation has been identified.


GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • Canadian Immunodeficiencies Patient Organization (CIPO)
    362 Concession Road 12
    RR #2
    Hastings Ontario K0L 1Y0
    Phone: 877-262-2476 (toll-free)
    Fax: 866-942-7651 (toll-free)
  • Jeffrey Modell Foundation/National Primary Immunodeficiency Resource Center
    747 Third Avenue
    New York NY 10017
    Phone: 866-463-6474 (toll-free); 212-819-0200
    Fax: 212-764-4180
  • European Society for Immunodeficiencies (ESID) Registry
    Dr. Gerhard Kindle
    University Medical Center Freiburg Centre of Chronic Immunodeficiency
    Engesserstr. 4
    79106 Freiburg
    Phone: 49-761-270-34450
  • Primary Immunodeficiency Diseases Registry at USIDNET
    40 West Chesapeake Avenue
    Suite 308
    Towson MD 21204-4803
    Phone: 866-939-7568
    Fax: 410-321-0293

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

X-Linked Agammaglobulinemia: Genes and Databases

Data are compiled from the following standard references: gene from HGNC; chromosome locus, locus name, critical region, complementation group from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD) to which links are provided, click here.

Table B.

OMIM Entries for X-Linked Agammaglobulinemia (View All in OMIM)


Normal allelic variants. BTK has 19 exons spread over 37 kb. Polymorphic variants that change the amino acid sequence in BTK are extremely rare. A single family in which a healthy boy had an amino acid substitution in the SH3 domain of the molecule has been reported [Pérez de Diego et al 2008]. Reference sequence NM_000061.2.

Pathologic allelic variants. More than 600 different mutations in BTK have been reported, and no single mutation accounts for more than 3% of individuals [Holinski-Feder et al 1998, Vihinen et al 1999, Conley et al 2005, Lindvall et al 2005, Väliaho et al 2006]. Two thirds of mutations are premature stop codons, splice defects, or frameshift mutations. These mutations result in improper processing of the BTK message. Therefore, no BTK message can be identified in the cytoplasm. Approximately one third of mutations are amino acid substitutions; however, approximately two thirds of these mutations appear to make the protein unstable (for more information, see Table A).

Normal gene product. The normal BTK product has 659 amino acid residues and is expressed in myeloid cells and platelets as well as B lineage cells. Reference sequence NP_000052.1.

Abnormal gene product. The protein is absent in more than 85% of individuals with XLA.


Literature Cited

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Chapter Notes

Revision History

  • 17 November 2011 (me) Comprehensive update posted live
  • 30 July 2009 (me) Comprehensive update posted live
  • 21 December 2005 (me) Comprehensive update posted to live Web site
  • 4 November 2004 (mec) Revision: test availability
  • 3 October 2003 (me) Comprehensive update posted to live Web site
  • 5 April 2001 (me) Review posted to live Web site
  • December 2000 (mec) Original submission
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