Immunodeficiency

Primary immunodeficiency diseases consist of a group of more than 100 inherited conditions, mostly monogenic, predisposing individuals to different sets of infections, allergy, autoimmunity and cancer. Primary immunodeficiencies therefore represent exquisite models of various immunopathological settings. The identification of the associated genes, 100 so far, has generated a plethora of information about the immune system and spurred the analysis of many aspects of the development, function and regulation of both innate and adaptive immunity. These findings can potentially contribute to improved care of affected individuals by providing new diagnostic and/or therapeutic tools. Several DNA repair pathways have evolved to recognise and repair DNA damaged by exogenous and endogenous agents, in order to maintain genomic integrity. Defects in these pathways can lead to replication errors, loss or rearrangement of genomic material, mutation or cancer and eventual death. The creation of many diverse lymphocyte receptors to identify potential pathogens has evolved by breaking and randomly resorting the gene segments coding for antigen receptors. Subsequent steps utilise the ubiquitous repair proteins. Individuals with defective repair pathways are increasingly recognized with immunodeficiency, many of whom exhibit radiosensitivity. Our understanding of the role of repair proteins in the development of adaptive immunity by VDJ recombination, antibody isotype class switching and affinity maturation by somatic hyper‑mutation has made significant progress over the last few years, partly by the identification of new genes involved in human disease. We describe the mechanisms involved in the development of adaptive immunity relating to DNA repair and describe the clinical consequences and treatment developments of primary immunodeficiency resulting from such defects.

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OMIM ID NAME PROTEINS TYPE ALIASES ABBREVIATIONS PATHWAY(S) RELATED
210900 Bloom syndrome RECQL3 (BLM) mental retardation (MR), skeletal abnormalities, risk of malignant disease, skin problem, chromosomal instability, immunodeficiency, sexual immaturity, sensitivity to radiation, telangiectasia Bloom–Torre–Machacek syndrome BLM
BL
BLS
Fanconi anemia (FA) pathway, homologous recombination (HR)
603554 Omenn syndrome DCLRE1C (Artemis) risk of malignant disease, skin problem, immunodeficiency RETICULOENDOTHELIOSIS, FAMILIAL, WITH EOSINOPHILIA
SEVERE COMBINED IMMUNODEFICIENCY WITH HYPEREOSINOPHILIA
non-homologous end-joining (NHEJ)
208900 ataxia-telangiectasia (AT) ATM neurodegenerative disease, blood cell cancer, psychomotor impairment, skeletal abnormalities, risk of malignant disease, chromosomal instability, immunodeficiency, sexual immaturity, sensitivity to radiation, CANCER, eye or vision problem Louis-Bar syndrome
AT, COMPLEMENTATION GROUP A, INCLUDED; ATA, INCLUDED
Boder-Sedgwick syndrome
AT
AT1
DNA damage response (DDR)
605258 immunodeficiency with hyper-IgM, TYPE 2 AICDA (AID) immunodeficiency HYPER-IgM SYNDROME 2 HIGM2
608184 immunodeficiency with hyper-IgM, TYPE 4 AICDA (AID) immunodeficiency HIGM4
254500 multiple myeloma (AL), resistance to LIG4 blood cell cancer, chromosomal instability, immunodeficiency SYSTEMIC AMYLOIDOSIS
AL AMYLOIDOSIS
AL non-homologous end-joining (NHEJ)
608106 immunodeficiency with hyper-IgM, TYPE 5 (HIGM5) UNG immunodeficiency HYPER-IgM SYNDROME 5 HIGM5 base excision repair (BER)
606593 LIG4 syndrome LIG4 mental retardation (MR), psychomotor impairment, skeletal abnormalities, risk of malignant disease, skin problem, chromosomal instability, immunodeficiency, sensitivity to radiation, facial anomalies, growth retardation, microcephaly LIG4S
LIG4
non-homologous end-joining (NHEJ)
242860 immunodeficiency-centromeric instability-facial anomalies syndrome (ICF) DNMT3B facial anomalies, immunodeficiency IMMUNE DEFICIENCY, VARIABLE, WITH CENTROMERIC INSTABILITY OF CHROMOSOMES 1, 9, AND 16
CENTROMERIC INSTABILITY, IMMUNODEFICIENCY SYNDROME; CIID
IMMUNODEFICIENCY SYNDROME, VARIABLE
ICF
CIID
DNA replication, heterochromatin formation
208920 early-onset ataxia with ocular motor apraxia and hypoalbuminemia/ataxia with oculomotor apraxia 1 (EAOH/AOA1) APTX neurodegenerative disease, psychomotor impairment, NO CANCER development, eye or vision problem, immunodeficiency ATAXIA EARLY-ONSET WITH OCULOMOTOR APRAXIA AND HYPOALBUMINEMIA
ataxia-oculomotor apraxia 1
EAOH
AOA
AOA1

EOCA-HA
EAOH/AOA1
251260 Nijmegen breakage syndrome (NBS) NBN (NBS1) microcephaly, risk of malignant disease, chromosomal instability, sensitivity to radiation, growth retardation, immunodeficiency ATAXIA-TELANGIECTASIA VARIANT V1
MICROCEPHALY WITH NORMAL INTELLIGENCE, IMMUNODEFICIENCY, AND LYMPHORETICULAR MALIGNANCIES
SEEMANOVA SYNDROME II
NONSYNDROMAL MICROCEPHALY, AUTOSOMAL RECESSIVE, WITH NORMAL INTELLIGENCE
IMMUNODEFICIENCY, MICROCEPHALY, AND CHROMOSOMAL INSTABILITY
BERLIN BREAKAGE SYNDROME
ATAXIA-TELANGIECTASIA VARIANT V2
NBS
AT-V1
BBS
AT-V2
homologous recombination (HR)
242900 Schimke immuno-osseous dysplasia (SIOD) SMARCAL1 skeletal abnormalities, immunodeficiency chromatin remodeling
611943 RIDDLE syndrome RNF168 mental retardation (MR), psychomotor impairment, sensitivity to radiation, facial anomalies, immunodeficiency RADIOSENSITIVITY, IMMUNODEFICIENCY, DYSMORPHIC FEATURES, AND LEARNING DIFFICULTIES RIDDLE
225750 Aicardi-Goutieres syndrome 1 (AGS1) TREX1 (DNase III) microcephaly, neurodegenerative disease, mental retardation (MR), skin problem, immunodeficiency AGS1 syndrome
AGS syndrome
encephalopathy, familial infantile, with intracranial calcification and chronic cerebrospinal fluid lymphocytosis
cree encephalitis
pseudotoxoplasmosis syndrome
Aicardi-Goutieres syndrome 1, autosomal dominant, included
AGS1
AGS
Fanconi anemia (FA) pathway
602450 severe combined immunodeficiency, Athabaskan type (SCIDA) DCLRE1C (Artemis), LIG4 immunodeficiency severe combined immunodeficiency
Athabaskan type SCID
severe combined immunodeficiency, Athabascan type
SCIDA non-homologous end-joining (NHEJ)
602450 severe combined immunodeficiency with radiation sensitivity (RS-SCID) DCLRE1C (Artemis) sensitivity to radiation, immunodeficiency severe combined immunodeficiency with sensitivity to ionizing radiation
SCID, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-POSITIVE, WITH SENSITIVITY TO IONIZING RADIATION
RS-SCID non-homologous end-joining (NHEJ)
152700 systemic lupus erythematosus (SLE) Ku70 (XRCC6), Ku80 (XRCC5) immunodeficiency lupus
lupus erythematosus
EXCESS LYMPHOCYTE LOW MOLECULAR WEIGHT DNA, INCLUDED
EXCESS LMW-DNA, INCLUDED
SLE non-homologous end-joining (NHEJ)
611291 severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation (SCID) NHEJ1 (Cernunnos) microcephaly, neurodegenerative disease, skeletal abnormalities, sensitivity to radiation, growth retardation, immunodeficiency SCID, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-POSITIVE, WITH SENSITIVITY TO IONIZING RADIATION
SEVERE COMBINED IMMUNODEFICIENCY, ATHABASKAN-TYPE, INCLUDED; SCIDA, INCLUDED
ATHABASKAN SEVERE COMBINED IMMUNODEFICIENCY, INCLUDED
severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation
NHEJ1-SCID non-homologous end-joining (NHEJ)

Last modification date: Aug. 17, 2011