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DOCK2 deficiency(IMD40)

MedGen UID:
901370
Concept ID:
C4225328
Disease or Syndrome
Synonym: Immunodeficiency 40
SNOMED CT: Dedicator of cytokinesis 2 deficiency (1197479002); DOCK2 deficiency (1197479002)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): DOCK2 (5q35.1)
 
Monarch Initiative: MONDO:0014637
OMIM®: 616433
Orphanet: ORPHA447737

Definition

Immunodeficiency-40 is an autosomal recessive primary form of combined immunodeficiency mainly affecting T-cell number and function, with other more variable defects in B-cell and NK-cell function. Patients have onset of severe invasive bacterial and viral infections in early childhood and may die without bone marrow transplantation (summary by Dobbs et al., 2015). [from OMIM]

Clinical features

From HPO
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Rectal fistula
MedGen UID:
19702
Concept ID:
C0034884
Anatomical Abnormality
The presence of a fistula affecting the rectum.
Intermittent diarrhea
MedGen UID:
66782
Concept ID:
C0239181
Sign or Symptom
Repeated episodes of diarrhea separated by periods without diarrhea.
Chronic diarrhea
MedGen UID:
96036
Concept ID:
C0401151
Finding
The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.
Focal active colitis
MedGen UID:
232511
Concept ID:
C1333625
Disease or Syndrome
Focal active colitis (FAC) is characterized by focal crypt damage caused by neutrophils. FAC is characterized by an inflammatory infiltrate consisting of intraepithelial neutrophils and/or neutrophils invading the lumen of the criptae, with no other microscopic alteration of the colonic mucosa and, in particular, without the presence of signs of chronic inflammation.
Macrovesicular hepatic steatosis
MedGen UID:
373290
Concept ID:
C1837256
Finding
A form of hepatic steatosis characterized by the presence of large, lipid-laden vesicles in the affected hepatocytes.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Respiratory tract infection
MedGen UID:
11199
Concept ID:
C0035243
Disease or Syndrome
An infection of the upper or lower respiratory tract.
Interstitial pneumonitis
MedGen UID:
61507
Concept ID:
C0206061
Disease or Syndrome
Inflammation of interstitial lung tissue, usually associated with infection.
Pulmonary infiltrates
MedGen UID:
116009
Concept ID:
C0235896
Finding
A finding indicating the presence of an inflammatory or neoplastic cellular infiltrate in the lung parenchyma.
Recurrent pneumonia
MedGen UID:
195802
Concept ID:
C0694550
Disease or Syndrome
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
Eosinophilic granuloma
MedGen UID:
4979
Concept ID:
C0014461
Neoplastic Process
A type of granuloma characterized morphologically by the predominance of Langerhans cells with characteristic grooved, folded, indented nuclei in the appropriate milieu that includes variable numbers of eosinophils and histiocytes including multinucleated forms, often appearing similar to osteoclasts or touton like giant cells, neutrophils and small lymphocytes. The concentration of the eosinophilic infiltrate varies from scattered mature cells to sheet-like masses of cells. Occasionally, areas of bone necrosis may interrupt the cellular infiltrate. The foamy cells may also be amassed in clumps, which are of no clinical significance because these clumps represent phagocytosis of lipid debris.
Recurrent otitis media
MedGen UID:
155436
Concept ID:
C0747085
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.
Combined immunodeficiency
MedGen UID:
751396
Concept ID:
C2711630
Disease or Syndrome
A group of phenotypically heterogeneous genetic disorders characterized by profound deficiencies of T- and B-cell function, which predispose the patients to both infectious and noninfectious complications.
T lymphocytopenia
MedGen UID:
419385
Concept ID:
C2931322
Finding
An abnormally low count of T cells.
Chronic oral candidiasis
MedGen UID:
870166
Concept ID:
C4024599
Disease or Syndrome
Chronic accumulation and overgrowth of the fungus Candida albicans on the mucous membranes of the mouth, generally manifested as associated with creamy white lesions on the tongue or inner cheeks, occasionally spreading to the gums, tonsils, palate or oropharynx.
Reduced antigen-specific T cell proliferation
MedGen UID:
1621145
Concept ID:
C4531148
Finding
Impaired proliferation and expansion of a T cell population following activation by an antigenic stimulus.
Severe varicella zoster infection
MedGen UID:
1688785
Concept ID:
C5139168
Disease or Syndrome
An unusually severe form of varicella zoster virus (VZV) infection. In the majority of the cases, especially in children, varicella is a very mild infection characterized by skin lesions, low grade fever and malaise. Severe infection is characterized by manifestations including VZV pneumonia, hepatitis, meningitis, and disseminated varicella.
Elevated circulating aspartate aminotransferase concentration
MedGen UID:
57497
Concept ID:
C0151904
Finding
The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal.
Elevated circulating alanine aminotransferase concentration
MedGen UID:
57740
Concept ID:
C0151905
Finding
An abnormally high concentration in the circulation of alanine aminotransferase (ALT).
Recurrent fever
MedGen UID:
811468
Concept ID:
C3714772
Sign or Symptom
Periodic (episodic or recurrent) bouts of fever.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDOCK2 deficiency

Professional guidelines

PubMed

Biggs CM, Keles S, Chatila TA
Clin Immunol 2017 Aug;181:75-82. Epub 2017 Jun 15 doi: 10.1016/j.clim.2017.06.003. PMID: 28625885Free PMC Article

Recent clinical studies

Etiology

Shakerian L, Nourizadeh M, Badalzadeh M, Fazlollahi MR, Shokouhi Shoormasti R, Saghafi S, Esmaeili B, Alizadeh Z, Borte S, Houshmand M, Hammarström L, Pourpak Z
Iran J Allergy Asthma Immunol 2021 Aug 7;20(4):402-412. PMID: 34418894

Diagnosis

Aytekin ES, Çağdaş D, Tan Ç, Çavdarlı B, Bilgiç I, Tezcan İ
Turk J Pediatr 2021;63(6):1072-1077. doi: 10.24953/turkjped.2021.06.016. PMID: 35023658
Shakerian L, Nourizadeh M, Badalzadeh M, Fazlollahi MR, Shokouhi Shoormasti R, Saghafi S, Esmaeili B, Alizadeh Z, Borte S, Houshmand M, Hammarström L, Pourpak Z
Iran J Allergy Asthma Immunol 2021 Aug 7;20(4):402-412. PMID: 34418894

Prognosis

Dobbs K, Domínguez Conde C, Zhang SY, Parolini S, Audry M, Chou J, Haapaniemi E, Keles S, Bilic I, Okada S, Massaad MJ, Rounioja S, Alwahadneh AM, Serwas NK, Capuder K, Çiftçi E, Felgentreff K, Ohsumi TK, Pedergnana V, Boisson B, Haskoloğlu Ş, Ensari A, Schuster M, Moretta A, Itan Y, Patrizi O, Rozenberg F, Lebon P, Saarela J, Knip M, Petrovski S, Goldstein DB, Parrott RE, Savas B, Schambach A, Tabellini G, Bock C, Chatila TA, Comeau AM, Geha RS, Abel L, Buckley RH, İkincioğulları A, Al-Herz W, Helminen M, Doğu F, Casanova JL, Boztuğ K, Notarangelo LD
N Engl J Med 2015 Jun 18;372(25):2409-22. doi: 10.1056/NEJMoa1413462. PMID: 26083206Free PMC Article

Clinical prediction guides

Guo X, Cai D, Dong K, Li C, Xu Z, Chen SY
Arterioscler Thromb Vasc Biol 2023 Jun;43(6):e210-e217. Epub 2023 Apr 6 doi: 10.1161/ATVBAHA.122.318400. PMID: 37021575Free PMC Article
Moens L, Gouwy M, Bosch B, Pastukhov O, Nieto-Patlàn A, Siler U, Bucciol G, Mekahli D, Vermeulen F, Desmet L, Maebe S, Flipts H, Corveleyn A, Moshous D, Philippet P, Tangye SG, Boisson B, Casanova JL, Florkin B, Struyf S, Reichenbach J, Bustamante J, Notarangelo LD, Meyts I
J Clin Immunol 2019 Apr;39(3):298-308. Epub 2019 Mar 5 doi: 10.1007/s10875-019-00603-w. PMID: 30838481Free PMC Article

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