MCID: HYP373
MIFTS: 33

Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

Categories: Genetic diseases, Rare diseases, Blood diseases, Bone diseases, Immune diseases, Skin diseases

Aliases & Classifications for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

MalaCards integrated aliases for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive:

Name: Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive 57 13 40
Hyperimmunoglobulin E Recurrent Infection Syndrome, Autosomal Recessive 53 25 75 29 6
Ar-Hies 53 25 75
Combined Immunodeficiency Due to Dock8 Deficiency 25 59
Hyperimmunoglobulin E Syndrome Type 2 25 75
Dock8 Immunodeficiency Syndrome 25 59
Cid Due to Dock8 Deficiency 25 59
Hies Autosomal Recessive 53 75
Dock8 Deficiency 53 25
Combined Immunodeficiency Due to Dedicator of Cytokinesis 8 Protein Deficiency 59
Hyper Ige Recurrent Infection Syndrome, Autosomal Recessive 25
Hyper-Ige Recurrent Infection Syndrome Autosomal Recessive 75
Hyper Immunoglobulin E Syndrome, Autosomal Recessive 25
Hyper-Immunoglobulin E Syndrome, Autosomal Recessive 73
Hyper Ig E Syndrome, Autosomal Recessive 53
Hyper-Ige Syndrome, Autosomal Recessive 57
Autosomal Recessive Hyper Ige Syndrome 53
Autosomal Recessive Hyper-Ige Syndrome 25
Hyper-Ige Syndrome Autosomal Recessive 75
Ar Hyperimmunoglobulin E Syndrome 53
Non-Skeletal Hyper-Ige Syndrome 25
Nonskeletal Hyper Ige Syndrome 75
Hies, Autosomal Recessive 57
Autosomal Recessive Hies 25

Characteristics:

Orphanet epidemiological data:

59
combined immunodeficiency due to dock8 deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: adolescent,late childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
early death may occur due to infection
distinct disorder from autosomal dominant hyper ige syndrome


HPO:

32
hyper-ige recurrent infection syndrome, autosomal recessive:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare immunological diseases


Summaries for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

NIH Rare Diseases : 53 Autosomal recessive hyper IgE syndrome (AR-HIES) is a very rare primary immunodeficiency syndrome characterized by highly elevated blood levels of immunoglobulin E (IgE), recurrent staphylococcal skin abscesses, and recurrent pneumonia. The same features are also seen in the more frequent autosomal dominant HIES syndrome. AR-HIES accounts for only a small minority of HIES cases, with about 130 affected families reported so far.In contrast to AD-HIES, the AR variant is further characterized by extreme hypereosinophilia (increase in the eosinophil count in the bloodstream); susceptibility to viral infections such as Herpes simplex and Molluscum contagiosum; involvement of the central nervous system; T-cell defects; and a high death rate. The dental, skeletal, connective tissue, and facial features present in AD-HIES are absent in AR-HIES. AR-HIES is inherited in an autosomal recessive fashion and is caused by mutations in the DOCK8 gene.

MalaCards based summary : Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive, also known as hyperimmunoglobulin e recurrent infection syndrome, autosomal recessive, is related to immunodeficiency 35 and hyper ige syndrome. An important gene associated with Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive is DOCK8 (Dedicator Of Cytokinesis 8). The drugs Busulfan and Cyclophosphamide have been mentioned in the context of this disorder. Affiliated tissues include skin, t cells and b cells, and related phenotypes are chronic otitis media and atopic dermatitis

OMIM : 57 Autosomal dominant hyper-IgE recurrent infection syndrome (147060) is a primary immunodeficiency disorder characterized by recurrent Staphylococcus aureus skin abscesses, increased serum IgE, and abnormalities of the connective tissue, skeleton, and dentition (Buckley et al., 1972; Grimbacher et al., 1999). The autosomal recessive form shares hyper-IgE, eosinophilia, and recurrent Staphylococcal infections, but is distinguished from autosomal dominant HIES by the lack of connective tissue and skeletal involvement (Renner et al., 2004). See also TYK2 deficiency (611521), a clinically distinct disease entity that includes characteristic features of both autosomal recessive HIES and mendelian susceptibility to mycobacterial disease (MSMD; 209950) (Minegishi et al., 2006). (243700)

UniProtKB/Swiss-Prot : 75 Hyperimmunoglobulin E recurrent infection syndrome, autosomal recessive: A rare disorder characterized by immunodeficiency, recurrent infections, eczema, increased serum IgE, eosinophilia and lack of connective tissue and skeletal involvement.

Genetics Home Reference : 25 Autosomal recessive hyper-IgE syndrome (AR-HIES) is a disorder of the immune system. A hallmark feature of the condition is recurrent infections that are severe and can be life-threatening. Skin infections can be caused by bacteria, viruses, or fungi. These infections cause rashes, blisters, accumulations of pus (abscesses), open sores, and scaling. People with AR-HIES also tend to have frequent bouts of pneumonia and other respiratory tract infections.

Related Diseases for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

Diseases in the Hyper-Ige Recurrent Infection Syndrome, Autosomal Dominant family:

Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

Diseases related to Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 immunodeficiency 35 11.4
2 hyper ige syndrome 10.2

Symptoms & Phenotypes for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

Symptoms via clinical synopsis from OMIM:

57
Respiratory Airways:
asthma

Laboratory Abnormalities:
eosinophilia
increased serum ige
decreased t cells
decreased b cells
decreased natural killer cells
more
Respiratory:
recurrent sinopulmonary infections

Neoplasia:
increased susceptibility to carcinomas, especially cancers related to cutaneous viral infections

Immunology:
recurrent bacterial infections
recurrent viral infections
recurrent fungal infections
impaired t cell immunity
impaired t cell proliferation and activation
more
Skin Nails Hair Skin:
atopic dermatitis
eczema, severe
skin abscesses, recurrent

Neurologic Central Nervous System:
increased neurologic sequelae of infections (rare)
hemiplegia (rare)
ischemic infarction (rare)
subarachnoid hemorrhage (rare)


Clinical features from OMIM:

243700

Human phenotypes related to Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive:

59 32 (show all 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 chronic otitis media 59 32 hallmark (90%) Very frequent (99-80%) HP:0000389
2 atopic dermatitis 59 32 hallmark (90%) Very frequent (99-80%) HP:0001047
3 pneumonia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002090
4 asthma 59 32 hallmark (90%) Very frequent (99-80%) HP:0002099
5 increased ige level 59 32 hallmark (90%) Very frequent (99-80%) HP:0003212
6 recurrent viral infections 59 32 Very frequent (99-80%) HP:0004429
7 severe viral infections 59 32 hallmark (90%) Very frequent (99-80%) HP:0005364
8 recurrent candida infections 59 32 hallmark (90%) Very frequent (99-80%) HP:0005401
9 decrease in t cell count 59 32 hallmark (90%) Very frequent (99-80%) HP:0005403
10 recurrent bacterial skin infections 59 32 hallmark (90%) Very frequent (99-80%) HP:0005406
11 b lymphocytopenia 59 32 hallmark (90%) Very frequent (99-80%) HP:0010976
12 recurrent sinusitis 59 32 hallmark (90%) Very frequent (99-80%) HP:0011108
13 onychomycosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0012203
14 skin ulcer 59 32 hallmark (90%) Very frequent (99-80%) HP:0200042
15 verrucae 59 32 hallmark (90%) Very frequent (99-80%) HP:0200043
16 squamous cell carcinoma 59 32 occasional (7.5%) Occasional (29-5%) HP:0002860
17 anal canal squamous carcinoma 59 32 occasional (7.5%) Occasional (29-5%) HP:0006763
18 squamous cell carcinoma of the vulva 59 32 occasional (7.5%) Occasional (29-5%) HP:0030417
19 recurrent respiratory infections 59 Very frequent (99-80%)
20 eczema 32 HP:0000964
21 eosinophilia 32 HP:0001880
22 subarachnoid hemorrhage 32 HP:0002138
23 hemiplegia 32 HP:0002301
24 neoplasm 32 HP:0002664
25 recurrent bacterial infections 32 HP:0002718
26 recurrent fungal infections 32 HP:0002841
27 cerebral vasculitis 32 HP:0005318
28 recurrent sinopulmonary infections 32 HP:0005425

Drugs & Therapeutics for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

Drugs for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 10)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Busulfan Approved, Investigational Phase 2 55-98-1 2478
2
Cyclophosphamide Approved, Investigational Phase 2 50-18-0, 6055-19-2 2907
3
Fludarabine Approved Phase 2 21679-14-1, 75607-67-9 30751
4
Lenograstim Approved, Investigational Phase 2 135968-09-1
5 Alkylating Agents Phase 2
6 Anesthetics Phase 2
7 Antineoplastic Agents, Alkylating Phase 2
8 Antirheumatic Agents Phase 2
9 Immunosuppressive Agents Phase 2
10 Yellow Dock Nutraceutical Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Pilot Study of Reduced-Intensity Hematopoietic Stem Cell Transplant of DOCK8 Deficiency Recruiting NCT01176006 Phase 2 Fludarabine(Fludara, Berlex Laboratories);Cyclophosphamide(CTX, Cytoxan);Busulfan (Busulfex)
2 Apheresis of Patients With Immunodeficiency Recruiting NCT01212055
3 Study of Clinical Features and Genetics of Hyperimmunoglobulin E Recurrent Infection Recruiting NCT00006150
4 Study of Voicing My CHOiCES as a Tool for Advanced Care Planning in Young Adults With Cancer Recruiting NCT02108028

Search NIH Clinical Center for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

Genetic Tests for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

Genetic tests related to Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Hyperimmunoglobulin E Recurrent Infection Syndrome, Autosomal Recessive 29 DOCK8

Anatomical Context for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

MalaCards organs/tissues related to Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive:

41
Skin, T Cells, B Cells

Publications for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

Articles related to Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive:

# Title Authors Year
1
Genetic, clinical, and laboratory markers for DOCK8 immunodeficiency syndrome. ( 21178272 )
2010

Variations for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

UniProtKB/Swiss-Prot genetic disease variations for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive:

75
# Symbol AA change Variation ID SNP ID
1 DOCK8 p.Lys473Arg VAR_063753 rs112321280

ClinVar genetic disease variations for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive:

6
(show top 50) (show all 180)
# Gene Variation Type Significance SNP ID Assembly Location
1 DOCK8 NM_203447.3(DOCK8): c.1418A> G (p.Lys473Arg) single nucleotide variant Pathogenic rs112321280 GRCh37 Chromosome 9, 336714: 336714
2 DOCK8 NM_203447.3(DOCK8): c.1418A> G (p.Lys473Arg) single nucleotide variant Pathogenic rs112321280 GRCh38 Chromosome 9, 336714: 336714
3 DOCK8 NM_203447.3(DOCK8): c.1126-395_2971-2751del deletion Pathogenic GRCh37 Chromosome 9, 333830: 394034
4 DOCK8 NM_203447.3(DOCK8): c.1126-395_2971-2751del deletion Pathogenic GRCh38 Chromosome 9, 333830: 394034
5 DOCK8 NM_203447.3(DOCK8): c.1126-395_2971-2751del deletion Pathogenic NCBI36 Chromosome 9, 323830: 384034
6 DOCK8 NC_000009.12: g.311734_398139del86406 deletion Pathogenic GRCh37 Chromosome 9, 311734: 398139
7 DOCK8 NC_000009.12: g.311734_398139del86406 deletion Pathogenic GRCh38 Chromosome 9, 311734: 398139
8 DOCK8 NM_203447.3(DOCK8): c.3494delC (p.Thr1165Lysfs) deletion Pathogenic rs113944762 GRCh38 Chromosome 9, 407033: 407033
9 DOCK8 NM_203447.3(DOCK8): c.3494delC (p.Thr1165Lysfs) deletion Pathogenic rs113944762 GRCh37 Chromosome 9, 407033: 407033
10 DOCK8 NM_203447.3(DOCK8): c.3504_3505insTGGCTGCT (p.Ala1169Trpfs) insertion Pathogenic rs886037645 GRCh38 Chromosome 9, 407043: 407044
11 DOCK8 NM_203447.3(DOCK8): c.3504_3505insTGGCTGCT (p.Ala1169Trpfs) insertion Pathogenic rs886037645 GRCh37 Chromosome 9, 407043: 407044
12 DOCK8 NM_203447.3(DOCK8): c.5433G> A (p.Glu1811=) single nucleotide variant Benign rs1887957 GRCh37 Chromosome 9, 441952: 441952
13 DOCK8 NM_203447.3(DOCK8): c.5433G> A (p.Glu1811=) single nucleotide variant Benign rs1887957 GRCh38 Chromosome 9, 441952: 441952
14 DOCK8 NM_203447.3(DOCK8): c.404+16delT deletion Benign/Likely benign rs727505303 GRCh37 Chromosome 9, 289597: 289597
15 DOCK8 NM_203447.3(DOCK8): c.404+16delT deletion Benign/Likely benign rs727505303 GRCh38 Chromosome 9, 289597: 289597
16 DOCK8 NM_203447.3(DOCK8): c.3022C> T (p.Arg1008Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs16937932 GRCh37 Chromosome 9, 396836: 396836
17 DOCK8 NM_203447.3(DOCK8): c.3022C> T (p.Arg1008Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs16937932 GRCh38 Chromosome 9, 396836: 396836
18 DOCK8 NM_203447.3(DOCK8): c.5001C> T (p.His1667=) single nucleotide variant Benign/Likely benign rs35662752 GRCh37 Chromosome 9, 434897: 434897
19 DOCK8 NM_203447.3(DOCK8): c.5001C> T (p.His1667=) single nucleotide variant Benign/Likely benign rs35662752 GRCh38 Chromosome 9, 434897: 434897
20 DOCK8 NM_203447.3(DOCK8): c.289C> A (p.Pro97Thr) single nucleotide variant Benign rs529208 GRCh37 Chromosome 9, 286593: 286593
21 DOCK8 NM_203447.3(DOCK8): c.289C> A (p.Pro97Thr) single nucleotide variant Benign rs529208 GRCh38 Chromosome 9, 286593: 286593
22 DOCK8 NM_203447.3(DOCK8): c.709G> A (p.Glu237Lys) single nucleotide variant Benign/Likely benign rs11789099 GRCh37 Chromosome 9, 312134: 312134
23 DOCK8 NM_203447.3(DOCK8): c.709G> A (p.Glu237Lys) single nucleotide variant Benign/Likely benign rs11789099 GRCh38 Chromosome 9, 312134: 312134
24 DOCK8 NM_203447.3(DOCK8): c.3573C> T (p.Ser1191=) single nucleotide variant Benign rs13285348 GRCh37 Chromosome 9, 414824: 414824
25 DOCK8 NM_203447.3(DOCK8): c.3573C> T (p.Ser1191=) single nucleotide variant Benign rs13285348 GRCh38 Chromosome 9, 414824: 414824
26 DOCK8 NM_203447.3(DOCK8): c.4107C> G (p.Leu1369=) single nucleotide variant Benign rs2297079 GRCh37 Chromosome 9, 421032: 421032
27 DOCK8 NM_203447.3(DOCK8): c.4107C> G (p.Leu1369=) single nucleotide variant Benign rs2297079 GRCh38 Chromosome 9, 421032: 421032
28 DOCK8 NM_203447.3(DOCK8): c.3058A> G (p.Ile1020Val) single nucleotide variant Conflicting interpretations of pathogenicity rs151094543 GRCh38 Chromosome 9, 396872: 396872
29 DOCK8 NM_203447.3(DOCK8): c.3058A> G (p.Ile1020Val) single nucleotide variant Conflicting interpretations of pathogenicity rs151094543 GRCh37 Chromosome 9, 396872: 396872
30 DOCK8 NM_203447.3(DOCK8): c.6019dupT (p.Tyr2007Leufs) duplication Pathogenic rs869312169 GRCh37 Chromosome 9, 452068: 452068
31 DOCK8 NM_203447.3(DOCK8): c.6019dupT (p.Tyr2007Leufs) duplication Pathogenic rs869312169 GRCh38 Chromosome 9, 452068: 452068
32 DOCK8 NC_000009.11: g.204193_343954del139762 deletion Pathogenic GRCh37 Chromosome 9, 204193: 343954
33 DOCK8 NM_203447.3(DOCK8): c.3840+3A> G single nucleotide variant Benign/Likely benign rs16938572 GRCh37 Chromosome 9, 418210: 418210
34 DOCK8 NM_203447.3(DOCK8): c.3840+3A> G single nucleotide variant Benign/Likely benign rs16938572 GRCh38 Chromosome 9, 418210: 418210
35 DOCK8 NM_203447.3(DOCK8): c.952G> A (p.Ala318Thr) single nucleotide variant Benign/Likely benign rs35482838 GRCh37 Chromosome 9, 328079: 328079
36 DOCK8 NM_203447.3(DOCK8): c.952G> A (p.Ala318Thr) single nucleotide variant Benign/Likely benign rs35482838 GRCh38 Chromosome 9, 328079: 328079
37 DOCK8 NM_203447.3(DOCK8): c.54-1G> T single nucleotide variant Pathogenic/Likely pathogenic rs192864327 GRCh37 Chromosome 9, 271626: 271626
38 DOCK8 NM_203447.3(DOCK8): c.54-1G> T single nucleotide variant Pathogenic/Likely pathogenic rs192864327 GRCh38 Chromosome 9, 271626: 271626
39 DOCK8 NM_203447.3(DOCK8): c.2749G> A (p.Glu917Lys) single nucleotide variant Uncertain significance rs200899164 GRCh37 Chromosome 9, 382656: 382656
40 DOCK8 NM_203447.3(DOCK8): c.2749G> A (p.Glu917Lys) single nucleotide variant Uncertain significance rs200899164 GRCh38 Chromosome 9, 382656: 382656
41 DOCK8 NM_203447.3(DOCK8): c.663C> A (p.Asp221Glu) single nucleotide variant Conflicting interpretations of pathogenicity rs139391329 GRCh38 Chromosome 9, 312088: 312088
42 DOCK8 NM_203447.3(DOCK8): c.663C> A (p.Asp221Glu) single nucleotide variant Conflicting interpretations of pathogenicity rs139391329 GRCh37 Chromosome 9, 312088: 312088
43 DOCK8 NM_203447.3(DOCK8): c.3606T> C (p.Cys1202=) single nucleotide variant Conflicting interpretations of pathogenicity rs143919622 GRCh37 Chromosome 9, 414857: 414857
44 DOCK8 NM_203447.3(DOCK8): c.3606T> C (p.Cys1202=) single nucleotide variant Conflicting interpretations of pathogenicity rs143919622 GRCh38 Chromosome 9, 414857: 414857
45 DOCK8 NM_203447.3(DOCK8): c.3813A> G (p.Lys1271=) single nucleotide variant Conflicting interpretations of pathogenicity rs75411647 GRCh37 Chromosome 9, 418180: 418180
46 DOCK8 NM_203447.3(DOCK8): c.3813A> G (p.Lys1271=) single nucleotide variant Conflicting interpretations of pathogenicity rs75411647 GRCh38 Chromosome 9, 418180: 418180
47 DOCK8 NM_203447.3(DOCK8): c.380G> A (p.Arg127His) single nucleotide variant Conflicting interpretations of pathogenicity rs150742426 GRCh37 Chromosome 9, 289557: 289557
48 DOCK8 NM_203447.3(DOCK8): c.380G> A (p.Arg127His) single nucleotide variant Conflicting interpretations of pathogenicity rs150742426 GRCh38 Chromosome 9, 289557: 289557
49 DOCK8 NM_203447.3(DOCK8): c.2739C> T (p.Ser913=) single nucleotide variant Benign/Likely benign rs116523732 GRCh38 Chromosome 9, 382646: 382646
50 DOCK8 NM_203447.3(DOCK8): c.2739C> T (p.Ser913=) single nucleotide variant Benign/Likely benign rs116523732 GRCh37 Chromosome 9, 382646: 382646

Expression for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

Search GEO for disease gene expression data for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive.

Pathways for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

GO Terms for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

Sources for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

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