Primary Antibody Deficiency Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
2687 ADA 81479,81479 Order Options and Pricing
AICDA 81479,81479
ATM 81408,81479
ATP6AP1 81479,81479
BLNK 81479,81479
BTK 81406,81479
CD19 81479,81479
CD40 81479,81479
CD40LG 81404,81479
CD79A 81479,81479
CD79B 81479,81479
CD81 81479,81479
CR2 81479,81479
ICOS 81479,81479
IGHM 81479,81479
IGLL1 81479,81479
IKZF1 81479,81479
IL21 81479,81479
INO80 81479,81479
IRF2BP2 81479,81479
LRBA 81479,81479
LRRC8A 81479,81479
MOGS 81479,81479
MRE11 81479,81479
MS4A1 81479,81479
NBN 81479,81479
NFKB1 81479,81479
NFKB2 81479,81479
NFKBIA 81479,81479
PIK3CD 81479,81479
PIK3R1 81479,81479
PLCG2 81479,81479
PRKCD 81479,81479
PTEN 81321,81323
PTPRC 81479,81479
RAG2 81479,81479
SH2D1A 81404,81403
TCF3 81479,81479
TNFRSF13B 81479,81479
TNFRSF13C 81479,81479
TNFSF12 81479,81479
TRNT1 81479,81479
TTC37 81479,81479
UNG 81479,81479
VAV1 81479,81479
XIAP 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
2687Genes x (46)81479 81321, 81323, 81403, 81404, 81406, 81408, 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Primary antibody deficiencies encompass a heterogeneous group of B-cell immunodeficiencies marked by reduced or absent antibody production. These disorders are highlighted by increased susceptibility to infection. The three categories of antibody deficiencies are common variable immunodeficiency (CVID), hyper IgM syndromes (HIGM) and agammaglobulinemia (AGG) (Bousfiha et al. 2018. PubMed ID: 29226301; Picard et al. 2018. PubMed ID: 29226302).

CVID is the most common primary immune deficiency affecting one in ~25,000 births. CVID is an immunodeficiency disorder hallmarked by impaired B cell differentiation and antibody production, namely IgG and IgA. CVID is primarily diagnosed via exclusion of other primary immune disorders. However, recurrent bacterial infections after two years of age, poor response of vaccines, and decreased IgG and IgA are indicative of CVID (Conley et al. 1999. PubMed ID: 10600329). About half of CVID patients also present with decreased serum IgM. CVID is a heterogeneous disorder affecting multiple organ systems and with symptoms ranging from autoimmune disease, chronic lung disease, bronchiectasis, gastrointestinal disease, malabsorption, granulomatous disease, liver disease, and/or lymphoma (Resnick et al. 2012. PubMed ID: 22180439; Conley et al. 2009. PubMed ID: 19302039). Due to the highly variable clinical presentation of CVID, median diagnostic delay is 4.1 years with 20% of patients being diagnosed before 20 years of age. The majority of patients with CVID are diagnosed between the ages of 20-45 years (Gathmann et al. 2014 PubMed ID: 24582312).

HIGM is due to impaired immunoglobulin class switch recombination (CSR) resulting in an increase in IgM and a decrease in IgG, IgA and IgE antibody levels. This humoral immunodeficiency leads to recurrent sinopulmonary infections, chronic diarrhea due to Cryptosporidium infection, and neutropenia presenting within the first or second decade of life. In severe cases, patients may also present with, sclerosing cholangitis, chronic arthritis, thrombocytopenia, hemolytic anemia, hypothyroidism, kidney disease and failure to thrive (Davies and Thrasher. 2010. PubMed ID: 20180797; Etzioni and Ochs. 2004. PubMed ID: 15319456; Leven et al. 2016. PubMed ID: 27189378).

Patients with agammaglobulinemia present with recurrent bacterial infections including Haemophilus influenza, Streptococcus pneumoniae, and staphylococci due to loss of antibody mediated immune responses. Common sites of infection include skin, respiratory tract, gastrointestinal tract, and joints. Severe infections can be life threatening due to infections spreading leading to empyema, meningitis, and sepsis. Infections typically occur after the first few months of life as maternal immunoglobulins are protective (Conley and Howard. 2011. PubMed ID: 20301626). Diagnosis primarily occurs in the first two years of life, although 10% of cases have delayed onset with immunodeficiency not being apparent until after ten years of age.

Genetics

In about 75% of CVID, a molecular diagnosis is not found. This is due to the multifactorial etiology of CVID including both genetic and environmental factors. Autosomal dominant CVIDs occur through pathogenic variants in the TNFRSF13B, IRF2BP2, NFKB1, NFKB2, VAV1, TNFSF12 and IKZF1 genes. Autosomal recessive CVIDs occur through pathogenic variants in the ICOS, IL21, CD81, MS4A1, NFKB2, CR2, LRBA, MOGS, TNFRSF13C, TTC37, or CD19 genes (Bousfiha et al. 2018. PubMed ID: 29226301; Picard et al. 2018. PubMed ID: 29226302). About 20% of CVID cases are due to pathogenic variants in the TNFRSF13B gene with ~90% of these cases being sporadic. Two missense variants, c.310T>C (p.Cys104Arg) and c.542C>A (p.Ala181Glu) are most commonly found and represent about 80% of all TNFRSF13B-related CVID cases (Salzer et al. 2009. PubMed ID: 18981294).

HIGM1 is inherited in an X-linked manner through pathogenic variants in the CD40LG gene. HIGM can also be inherited in an autosomal recessive manner through pathogenic variants in the AICDA, CD40, INO80 or UNG genes. About 75% of cases to date are due to pathogenic variants in the CD40LG gene (Johnson et al. 2013. PubMed ID: 20301576). Other syndromes inherited in an X-linked recessive manner that also exhibit increased IgM levels include agammaglobulinemia (BTK), and lymphoproliferative syndrome (SH2D1A). Related autosomal dominant disorders include primary immunodeficiency (PIK3CD) and ectodermal dysplasia (NFKBIA). Autosomal recessive conditions include ataxia telangiectasia (ATM), Nijmegen breakage syndrome (NBN), and ataxia telangiectasia like disorder (MRE11) (Bousfiha et al. 2018. PubMed ID: 29226301; Picard et al. 2018. PubMed ID: 29226302).

X-linked agammaglobulinemia represents about 85% of AGG cases via pathogenic variants in the BTK gene. To date over 700 different pathogenic variants in the BTK gene have been reported with no single pathogenic variant representing more than 3% of XLA cases (Conley et al. 2005. PubMed ID: 15661032; Lindvall et al. 2005. PubMed ID: 15661031; Väliaho et al. 2006. PubMed ID: 16969761). Autosomal recessive forms of AGG are due to pathogenic variants in the BLNK, CD79A, CD79B, IGHM, IGLL1, MOGS, PIK3R1, TRNT1 and SH2D1A genes. AGG via pathogenic variants in the LRRC8 and TCF3 genes are inherited in an autosomal dominant manner (Bousfiha et al. 2018. PubMed ID: 29226301; Picard et al. 2018. PubMed ID: 29226302).

See individual gene test descriptions for information on molecular biology of gene products and mutation spectra.

Clinical Sensitivity - Sequencing with CNV PGxome

In a study of 50 patients with common variable immunodeficiency, a genetic diagnosis was found in 15 cases. Pathogenic variants were identified in the TNFRSF13B (14%), NFKB1 (10%), STAT3 (6%), CTLA4 (4%), PIK3CD (2%), IZKF1 (2%), LRBA (4%), and STXBP2 (2%) genes (Maffucci et al. 2016. PubMed ID: 27379089).

In a molecular study of 140 patients presenting with hyper IgM syndromes based on recurrent and/or severe infections, elevated IgM, and reduced IgA and IgG levels, sequencing of the CD40LG, CD40, NEMO, AICDA, UNG, ICOS, ICOSL, BTK, and SH2D1 genes was performed. Pathogenic variants were found in 103 of 140 patients with pathogenic variants in the CD40LG, AICDA, UNG, NEMO, and BTK genes accounting for 92%, 4%, 1%, 1%, and 3% of cases respectively (Lee et al. 2005. PubMed ID: 15358621).

X-linked agammaglobulinemia accounts for 90% of cases of agammaglobulinemia in males through pathogenic variants in the BTK gene. Autosomal recessive forms of agammaglobulinemia through pathogenic variants in the IGHM, CD79A, CD79B, or BLNK genes represent 10% of cases in males (Conley and Howard. 2011. PubMed ID: 20301626; Conley et al. 1998. PubMed ID: 9545398; Kanegane et al. 2001. PubMed ID: 11742281).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 99.2% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates for testing include individuals with decreased serum immunoglobulin levels for IgG, IgA and/or IgM and normal B cell levels. In the case of HIGM, individuals typically present with decreased IgG and IgA levels, but elevated IgM (Bonilla et al. 2015. PubMed ID: 26371839). Patients with primary antibody deficiencies generally present with recurrent and/or severe respiratory infections, recurrent otitis media, sinusitis and pneumonia. Respiratory infections involving Streptococcus pneumoniae and Haemophilus influenza are common features. Other clinical findings may include failure to thrive, recurrent fevers, chronic diarrhea, nodal lymphoid hyperplasia in the gut or unexplained hepatosplenomegaly. Autoimmune disease may also be present, but is typically found in adults (Bousfiha et al. 2018. PubMed ID: 29226301; Picard et al. 2018. PubMed ID: 29226302).

Diseases

Name Inheritance OMIM ID
Agammaglobulinemia 1 AR 601495
Agammaglobulinemia 2, Autosomal Recessive AR 613500
Agammaglobulinemia 3, Autosomal Recessive AR 613501
Agammaglobulinemia 4, Autosomal Recessive AR 613502
Agammaglobulinemia 5, Autosomal Dominant AD 613506
Agammaglobulinemia 6, Autosomal Recessive AR 612692
Agammaglobulinemia 7, Autosomal Recessive AR 615214
Agammaglobulinemia 8, autosomal dominant AD 616941
Ataxia-Telangiectasia Syndrome AR 208900
Ataxia-Telangiectasia-Like Disorder AR 604391
Autoimmune Lymphoproliferative Syndrome, Type III AR 615559
Autoinflammation, antibody deficiency, and immune dysregulation syndrome AD 614878
Combined Cellular And Humoral Immune Defects With Granulomas AR 233650
Common Variable Agammaglobulinemia AD 240500
Congenital Disorder Of Glycosylation Type IIb AR 606056
Cowden Disease 158350
Ectodermal Dysplasia, Anhidrotic, With T-Cell Immunodeficiency, Autosomal Dominant AD 612132
Hepatitis C Virus, Susceptibility To 609532
Immunodeficiency 14 AD 615513
Immunodeficiency 36 AD 616005
Immunodeficiency and Hepatopathy with Cutis Laxa XL 300972
Immunodeficiency With Hyper Igm Type 1 XL 308230
Immunodeficiency With Hyper IgM Type 2 AR 605258
Immunodeficiency With Hyper IgM Type 3 AR 606843
Immunodeficiency With Hyper IgM Type 5 AR 608106
Immunodeficiency, Common Variable, 1 AR 607594
Immunodeficiency, common variable, 10 AD 615577
Immunodeficiency, common variable, 11 AR 615767
Immunodeficiency, common variable, 12 AD 616576
Immunodeficiency, common variable, 13 AD 616873
Immunodeficiency, common variable, 14 AD 617765
Immunodeficiency, Common Variable, 3 AR 613493
Immunodeficiency, Common Variable, 4 AR 613494
Immunodeficiency, Common Variable, 5 AR 613495
Immunodeficiency, Common Variable, 6 AR 613496
Immunodeficiency, common variable, 7 AR 614699
Immunodeficiency, Common Variable, 8, with Autoimmunity AR 614700
Immunoglobulin A Deficiency 2 AD 609529
Lymphoproliferative Syndrome, X-Linked, 1 XL 308240
Lymphoproliferative Syndrome, X-Linked, 2 XL 300635
Nijmegen Breakage Syndrome AR 251260
Omenn Syndrome AR 603554
Severe Combined Immunodeficiency Due To Ada Deficiency AR 102700
Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Positive, Nk Cell-Positive AR 608971
Severe Immunodeficiency, Autosomal Recessive, T-Cell Negative, B-Cell Negative, NK Cell-Positive AR 601457
Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay AR 616084
Systemic Lupus Erythematosus 9 AR 610927
Trichohepatoenteric syndrome 1 AR 222470
X-Linked Agammaglobulinemia XL 300755
X-Linked Agammaglobulinemia With Growth Hormone Deficiency XL 307200

Related Tests

Name
PGxome®
Common Variable Immune Deficiency (CVID) Panel
Hyper IgM Syndrome Panel

Citations

  • Bonilla et al. 2015 PubMed ID: 26371839
  • Bousfiha et al. 2018 PubMed ID: 29226301
  • Conley and Howard. 2011. PubMed ID: 20301626
  • Conley et al. 1998. PubMed ID: 9545398
  • Conley et al. 1999. PubMed ID: 10600329
  • Conley et al. 2005 PubMed ID: 15661032
  • Conley et al. 2009. PubMed ID: 19302039
  • Davies and Thrasher. 2010. PubMed ID: 20180797
  • Etzioni and Ochs. 2004. PubMed ID: 15319456
  • Gathmann et al. 2014 PubMed ID: 24582312
  • Johnson et al. 2013 PubMed ID: 20301576
  • Kanegane et al. 2001. PubMed ID: 11742281
  • Lee et al. 2005. PubMed ID: 15358621
  • Leven et al. 2016. PubMed ID: 27189378
  • Lindvall et al. 2005. PubMed ID: 15661031
  • Maffucci et al. 2016 PubMed ID: 27379089
  • Picard et al. 2018 PubMed ID: 29226302
  • Resnick et al. 2012 PubMed ID: 22180439
  • Salzer et al. 2009. PubMed ID: 18981294
  • Väliaho et al. 2006. PubMed ID: 16969761

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

loading Loading... ×

ORDER OPTIONS

View Ordering Instructions

1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Total Price: $
×
Copy Text to Clipboard
×