Version May 2024
| Disease | Genetic defect | Inheritance | OMIM | Immunoglobulin | Associated features |
| Severe reduction in all serum immunoglobulin isotypes with profoundly decreased or absent B cells, agammaglobulinemia | |||||
| BTK deficiency, XL agammaglobulinemia (XLA) | Bruton tyrosine kinase (BTK) | XL | 300300 | All isotypes decreased in major of patients; some patients have detectable immunoglobulins | Severe bacterial infections, normal numbers of pro-B cells |
| Mu heavy-chain deficiency | Immunoglobulin heavy constant mu (IGHM) | AR | 147020 | All isotypes decreased | Severe bacterial infections normal numbers of pro-B cells |
| Lambda 5 deficiency | Immunoglobulin lambda-like polypeptide 1 (IGLL1) | AR | 146770 | All isotypes decreased | Severe bacterial infections, normal numbers of pro-B cells |
| Immunoglobulin alpha deficiency | CD79a molecule (CD79A) | AR | 112205 | All isotypes decreased | Severe bacterial infections, normal numbers of pro-B cells |
| Immunoglobulin beta deficiency | CD79b molecule (CD79B) | AR | 147245 | All isotypes decreased | Severe bacterial infections, normal numbers of pro-B cells |
| BLNK deficiency | B cell linker (BLNK) | AR | 604515 | All isotypes decreased | Severe bacterial infections, normal numbers of pro-B cells |
| p110 delta deficiency | Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD) | AR | 602839 | All isotypes decreased | Severe bacterial infections, autoimmune complications (IBD) |
| p85 deficiency | Phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) | AR | 615214 | All isotypes decreased | Severe bacterial infections, cytopenias, decreased or absent pro-B cells |
| E47 transcription factor deficiency | Transcription factor 3 (TCF3) | AD | 616941 | All isotypes decreased | Recurrent bacterial infections |
| AR | 147141 | All isotypes decreased | Severe, recurrent bacterial infections; failure to thrive | ||
| SLC39A7 (ZIP7) deficiency | Solute carrier family 39 member 7 (SLC39A7) | AR | 601416 | All isotypes decreased | Early-onset infections, blistering dermatosis, failure to thrive, thrombocytopenia |
| Hoffman syndrome/TOP2B deficiency | DNA topoisomerase II beta (TOP2B) | AD | 126431 | All isotypes decreased | Recurrent infections, facial dysmorphism, limb anomalies |
| FNIP1 deficiency | Folliculin interacting protein 1 (FNIP1) | AR | 619705 | All isotypes decreased | Early-onset recurrent infections, bronchiectasis, fibrosis, interstitial pneumoniae, neutropenia (severe or intermittent, Crohn disease (1 patient), congenital heart defects, muscular hypotonia, developmental delay |
| PU1 deficiency | Spi-1 proto-oncogene (SPI1) | AD | 619707 | All isotypes decreased | Sinopulmonary infections with encapsulated bacteria, viral infections |
| Severe reduction in at least 2 serum immunoglobulin isotypes with normal or low number of B cell, CVID phenotype | |||||
| CVID with no gene defect specified | Unknown | Variable | Low IgG and IgA and/or IgM | Clinical phenotypes vary; most have recurrent infections; some have polyclonal lymphoproliferation, autoimmune cytopenias, and/or granulomatous disease | |
| Activated p110 delta syndrome (APDS) | Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD) GOF | AD | 615513 (APDS1) | Normal/increased IgM; reduced IgG and IgA | Severe bacterial infections, reduced memory B cells and increased transitional B cells, EBV and/or CMV viremia, lymphadenopathy/splenomegaly, autoimmunity, lymphoproliferation, lymphoma |
| Phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) | AD | 616005 (APDS2) | Normal/increased IgM; reduced IgG and IgA | Severe bacterial infections, reduced memory B cells and increased transitional B cells, lymphadenopathy/splenomegaly, lymphoproliferation, lymphoma, developmental delay | |
| PTEN deficiency (LOF) | Phosphatase and tensin homolog (PTEN) | AD | 158350 | Normal/decreased | Recurrent infections, lymphoproliferation, autoimmunity, developmental delay |
| CD19 deficiency | CD19 molecule (CD19) | AR | 107265 | Low IgG and IgA and/or IgM | Recurrent infections, may have glomerulonephritis |
| CD81 deficiency | CD81 molecule (CD81) | AR | 186845 | Low IgG; low or normal IgA and IgM | Recurrent infections, may have glomerulonephritis (CD81 mutation abolishes expression of CD19, thereby phenocopying CD19 mutations) |
| CD20 deficiency | Membrane spanning 4-domains A1 (MS4A1) | AR | 112210 | Low IgG; normal or elevated IgM and IgA | Recurrent infections |
| CD21 deficiency | Complement C3d receptor 2 (CR2) | AR | 120650 | Low IgG; impaired anti-pneumococcal response | Recurrent infections |
| TACI deficiency* | TNF receptor superfamily member 13B (TNFRSF13B) | AR or AD | 604907 | Low IgG and IgA and/or IgM | Variable clinical expression nand penetrance for monoallelic variants |
| BAFF receptor deficiency | TNF receptor superfamily member 13C (TNFRSF13C) | AR | 606269 | Low IgG and IgM | Variable clinical expression |
| TWEAK deficiency | TNF superfamily member 12 (TNFSF12) | AD | 602695 | Low IgM and IgA; lack of anti-pneumococcal antibody | Pneumonia, bacterial infections, warts, thrombocytopenia, neutropenia |
| TRNT1 deficiency | tRNA nucleotidyl transferase 1 (TRNT1) | AR | 612907 | B cell deficiency and hypogammaglobulinemia | Congenital sideroblastic anemia, deafness, developmental delay |
| NFKB1 deficiency | Nuclear factor kappa B subunit 1 (NFKB1) | AD | 164011 | Normal or low IgG, IgA, and IgM; low or normal B cells; low memory B cells | Recurrent sinopulmonary infections, COPD, EBV proliferation, autoimmune cytopenias, alopecia and autoimmune thyroiditis |
| NFKB2 deficiency | Nuclear factor kappa B subunit 2 (NFKB2) | AD | 615577 | Low serum IgG, IgA, and IgM; low B cell numbers | Recurrent sinopulmonary infections, alopecia and endocrinopathies |
| IKAROS deficiency | IKAROS family zinc finger 1 (IKZF1) | AD (haploinsufficiency) | 603023 | Low IgG, IgA, and IgM; low or normal B cells; B cells and immunoglobulin levels reduce with age | Decreased pro-B cells, recurrent sinopulmonary infections, increased risk of ALL, autoimmunity, CVID phenotype |
| IRF2BP2 deficiency | Interferon regulatory factor 2 binding protein 2 (IRF2BP2) | AD | 615332 | Hypogammaglobulinemia; absent IgA | Recurrent infections, possible autoimmunity and inflammatory disease |
| ATP6AP1 deficiency | ATPase H+ transporting accessory protein 1 (ATP6AP1) | XL | 300972 | Variable immunoglobulin findings | Hepatopathy, leukopenia, low copper |
| ARHGEF1 deficiency | Rho guanine nucleotide exchange factor 1 (ARHGEF1) | AR | 618459 | Hypogammaglobulinemia; lack of antibody | Recurrent infections, bronchiectasis |
| SH3KBP1 (CIN85) deficiency | SH3 domain containing kinase binding protein 1 (SH3KBP1) | XL | 300310 | IgM and IgG deficiency; loss of antibody | Severe bacterial infections |
| SEC61A1 deficiency | SEC61 translocon subunit alpha 1 (SEC61A1) | AD | 609213 | Hypogammaglobulinemia | Severe recurrent respiratory tract infections |
| RAC2 deficiency | Rac family small GTPase 2 (RAC2) | AR | 602049 | Low IgG, IgA, and IgM; low or normal B cells; reduced antibody responses following vaccination | Recurrent sinopulmonary infections, selective IgA deficiency, poststreptococcal glomerulonephritis, urticaria |
| Mannosyl-oligosaccharide glucosidase deficiency | Mannosyl-oligosaccharide glucosidase (MOGS) | AR | 601336 | Low IgG, IgA, and IgM; increased B cells; poor antibody responses following vaccination | Bacterial and viral infections, severe neurologic disease; also known as CDG-IIb |
| PIK3CG deficiency | Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG) | AR | 619802 | Reduced memory B cells; hypogammaglobulinemia | Recurrent infections, cytopenia/lymphopenia, eosinophilia, splenomegaly, lymphadenopathy, HLH-like |
| BOB1 deficiency | POU class 2 homeobox associating factor 1 (POU2AF1) | AR | Reduced memory B cells; agammaglobulinemia | Recurrent respiratory infections, possible chronic viral infection of CNS with progressive tetraparesia | |
| Severe reduction in serum IgG and IgA with normal/elevated IgM and normal numbers of B cells, hyper-IgM | |||||
| AID deficiency | Activation-induced cytidine deaminase (AICDA) | AR | 605258 | IgG and IgA decreased; IgM increased; normal memory B cell but lacking somatic hypermutation | Bacterial infections, enlarged lymph nodes and germinal centers, autoimmunity |
| AD | 605257 | IgG absent or decreased; IgA undetected; IgM increased; normal memory B cells with intact somatic hypermutation | Bacterial infections, enlarged lymph nodes and germinal centers, mutations uniquely localize to the nuclear export signal | ||
| UNG deficiency | Uracil DNA glycosylase (UNG) | AR | 191525 | IgG and IgA decreased; IgM increased | Enlarged lymph nodes and germinal centers |
| INO80 deficiency | INO80 complex ATPase subunit (INO80) | AR | 610169 | IgG and IgA decreased; IgM increased | Severe bacterial infections |
| MSH6 deficiency | MutS homolog 6 (MSH6) | AR | 600678 | Variable IgG defects; increased IgM in some; normal B cells; low switched memory B cells; immunoglobulin class-switch recombination and somatic hypermutation defects | Family or personal history of cancer |
| CTNNBL1 deficiency | Catenin beta-like 1 (CTNNBL1) | AR | Reduced memory B cells; immunoglobulin class-switch recombination an somatic hypermutation defects; progressive hypogammaglobulinemia | CVID, autoimmune cytopenias, recurrent infections, hyperplastic germinal centers | |
| APRIL deficiency | TNF superfamily member 13 (TNFSF13) | AR | Normal total B cell counts; reduced memory B cells; hypogammaglobulinemia | CVID, chronic but mild infections, alopecia areata | |
| Isotype, light chain, or functional deficiencies with generally normal numbers of B cell | |||||
| Immunoglobulin heavy-chain mutations and deletions | Mutation or chromosomal deletion at 14q32 | AR | One or more IgG and/or IgA subclasses as well as IgE may be absent | May be asymptomatic | |
| Kappa chain deficiency | Immunoglobulin kappa constant (IGKC) | AR | 147200 | All immunoglobulins have lambda light chain | Asymptomatic |
| Isolated IgG subclass deficiency | Unknown | Unknown | Reduction in one or more IgG subclass | Usually asymptomatic; a minority may have poor antibody response to specific and recurrent viral/bacterial infections | |
| IgG subclass deficiency with IgA deficiency | Unknown | Unknown | Reduced IgA with decreased in one or more IgG subclass | Recurrent bacterial infections; may be asymptomatic | |
| Selective IgA deficiency | Unknown | Unknown | Absent IgA with other isotypes normal; normal subclasses and specific antibodies | May be asymptomatic; bacterial infections; autoimmunity mildly increased | |
| Specific antibody deficiency with normal immunoglobulin levels and normal B cells | Unknown | Unknown | Normal | Reduced ability to produce antibodies to specific antigens | |
| Transient hypogammaglobulinemia of infancy | Unknown | Unknown | IgG and IgA decreased | Normal ability to produce antibodies to vaccine antigens, usually not associated with significant infections | |
| CARD11 GOF | Caspase recruitment domain family member 11 (CARD11) | AD GOF | 616452 | Polyclonal B cell lymphocytosis due to constitutive NFkB activation | Splenomegaly, lymphadenopathy, poor vaccine response |
| Selective IgM deficiency | Unknown | Unknown | Absent serum IgM | Pneumococcal/bacterial | |
IUIS: International Union of Immunological Societies; XL: X linked; AR: autosomal recessive; IBD: inflammatory bowel disease; AD: autosomal dominant; ZIP7: zinc transporter 7; DNA: deoxyribonucleic acid; PU1: hematopoietic transcription factor PU.1; CVID: common variable immunodeficiency; IgG: immunoglobulin G; IgA: immunoglobulin A; IgM: immunoglobulin M; GOF: gain of function; EBV: Epstein-Barr virus; CMV: cytomegalovirus; LOF: loss of function; CD: cluster of differentiation; TACI: transmembrane activator and calcium modulator and cyclophilin ligand interactor; TNF: tumor necrosis factor; BAFF: B cell activating factor; TWEAK: TNF-related weak inducer of apoptosis; tRNA: transfer ribonucleic acid; COPD: chronic obstructive pulmonary disease; ALL: acute lymphoblastic leukemia; CIN85: Cbl-interacting 85 kDa protein; CDG-IIb: congenital disorder of glycosylation type IIb; HLH: hemophagocytic lymphohistiocytosis; BOB1: B cell-specific octamer binding protein 1; CNS: central nervous system; AID: activation-induced cytidine deaminase; APRIL: A proliferation-inducing ligand; IgE: immunoglobulin E; NFkB: nuclear factor kappa B; WHIM: warts, hypogammaglobulinemia, infections, myelokathexis; ICF: immunodeficiency with centromeric instability and facial anomalies; VODI: veno-occlusive disease with immunodeficiency.
* Heterozygous variants in TNFRSF13B have been detected in healthy individuals; thus, such variants are likely to be disease modifying rather than disease causing.آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
