Information on IMD107
Basic details
Name: Immunodeficiency 107 | Acronym: IMD107
Alt. names: Otulin haploinsufficiency | Immunodeficiency 107, susceptibility to invasive staphylococcus aureus infections
Gene: OTULIN | MOI: Autosomal dominant | Mechanism of action: Haploinsufficiency
No. of cases in DB: 17 | First reported in: 2022
Last updated on: 2023-12-01 13:42:09 by Andrés Caballero-Oteyza
Description
It is characterized most often by the development of invasive and severe life-threatening infections with S. aureus affecting the skin and/or lungs. There is incomplete penetrance (about 35%) and variable expressivity. In some patients with heterozygous OTULIN mutations, an infectious agent is not identified, suggesting that low-grade infectious or even noninfectious triggers may play a role in development of the disease. The levels and function of immune cells appear normal; the molecular defect resides in fibroblasts and possibly other nonhematopoietic barrier cells that show increased susceptibility to the detrimental effects of the S. aureus alpha-toxin (Spaan et al., 2022)[souce: OMIM].
Management
Description of management option has not been reviewed yet.
17 reported cases added to GenIA
| SubjectID | Sex | Fam.ID | AD | AFM | Validity | Country | Population | Reference & Pub.code |
|---|---|---|---|---|---|---|---|---|
104576 |
F | 215552 |
39 | Turkey | Turkish | PMID:27559085 [Fam.2:I.1]; PMID:35587511 [Fam.I:I.1(1)]; PMID:38914362 [Fam.B:I.2(034)] | ||
| 104582 |
M | 215553 |
43 | Turkey | Turkish | PMID:27559085 [Fam.3:I.2]; PMID:35587511 [Fam.H:I.2(2)]; PMID:38914362 [Fam.C:I.1(037)] | ||
| 104604 |
M | 215555 |
Iran | Iranian | PMID:30796585 [Fam.Patient:IV.2]; PMID:35587511 [Fam.J:I.2(2)]; PMID:38914362 [Fam.E:IV.2(062)] | |||
| 104619 |
M | 215558 |
19 | 19 | Netherlands | Dutch | PMID:35587511 [Fam.A:II.3(5)]; PMID:38914362 [Fam.G:II.3(075)] | |
| 104620 |
F | 215558 |
60 | Netherlands | Dutch | PMID:35587511 [Fam.A:I.1(1)]; PMID:38914362 [Fam.G:I.2(072)] | ||
| 104644 |
M | 215563 |
70 | 14 | Argentina | Argentinian | PMID:35587511 [Fam.B:III.2(5)]; PMID:38914362 [Fam.H:III.1(080)] | |
| 104645 |
F | 215563 |
Argentina | Argentinian | PMID:35587511 [Fam.B:I.1(1)]; PMID:38914362 [Fam.H:I.2(077)] | |||
| 104647 |
F | 215563 |
Argentina | Argentinian | PMID:35587511 [Fam.B:II.1(3)]; PMID:38914362 [Fam.H:II.2(079)] | |||
| 104650 |
M | 215563 |
72 | Argentina | Argentinian | PMID:35587511 [Fam.B:III.3(6)]; PMID:38914362 [Fam.H:III.3(082)] | ||
| 104651 |
M | 215563 |
37 | Argentina | Argentinian | PMID:35587511 [Fam.B:IV.1(7)]; PMID:38914362 [Fam.H:IV.1(083)] | ||
| 104653 |
M | 215564 |
19 | 4 | Mexico | Mexican | PMID:35587511 [Fam.C:III.1(5)]; PMID:38914362 [Fam.I:III.1(089)] | |
| 104656 |
M | 215565 |
11 | 2 | France | French | PMID:35587511 [Fam.D:II.3(5)]; PMID:38914362 [Fam.J:II.3(094)] | |
| 104661 |
F | 215566 |
35 | Belgium | Belgian | PMID:35587511 [Fam.E:II.3(5)]; PMID:38914362 [Fam.K:II.3(099)] | ||
| 104665 |
F | 215566 |
35 | Belgium | Belgian | PMID:35587511 [Fam.E:II.2(4)]; PMID:38914362 [Fam.K:II.2(098)] | ||
| 104666 |
M | 215567 |
46 | 42 | France | French | PMID:35587511 [Fam.F:II.1(3)]; PMID:38914362 [Fam.L:II.1(102)] | |
| 105413 |
F | 215763 |
31 | 1 | Netherlands | PMID:38914362 [Fam.P:II.1(116)]; PMID:38129331 [case(II.1)] | ||
| 106288 |
F | 215980 |
41 | 15 | Possible | Spain | PMID:38914362 [Fam.Q:II.6(125)]; PMID:38578307 [Fam.1:II.5(Patient)] |
AD: Age at genetic diagnosis; AFM: age at first manifestation; PMID: PubMed ID; GRID: GenIA reference ID (ref. not in PubMed).
Summary of clinical findings
[Considering only Definitive and Possible cases]
| Rank | Clinical term | Present | Absent | Unreported |
|---|---|---|---|---|
| 1 | (unusual) Respiratory tract infection |
9 (52.9%) | 0 (0.0%) | 8 (47.1%) |
| 2 | Lung disease |
9 (52.9%) | 0 (0.0%) | 8 (47.1%) |
| 3 | Pneumonia |
9 (52.9%) | 0 (0.0%) | 8 (47.1%) |
| 4 | (Unusual) bacterial infection |
5 (29.4%) | 1 (5.9%) | 11 (64.7%) |
| 5 | Chronic furunculosis |
5 (29.4%) | 0 (0.0%) | 12 (70.6%) |
| 6 | Cutaneous necrosis |
3 (17.7%) | 0 (0.0%) | 14 (82.4%) |
| 7 | Recurrent S. aureus infections |
3 (17.7%) | 3 (17.7%) | 11 (64.7%) |
| 8 | Septicaemia |
2 (11.8%) | 0 (0.0%) | 15 (88.2%) |
| 9 | Cutaneous abscess |
2 (11.8%) | 0 (0.0%) | 15 (88.2%) |
| 10 | Skin infections |
2 (11.8%) | 0 (0.0%) | 15 (88.2%) |
| 11 | Pyoderma gangrenosum |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 12 | Neutrophilic infiltration of the skin |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 13 | Methicillin-resistant S. aureus infection |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 14 | Systemic autoinflammation |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 15 | Reduced IgG2 levels |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 16 | Cellulitis |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 17 | Septic Shock |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 18 | neutralising alpha-toxin antibodies |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 19 | Chorioamnionitis |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 20 | Fever |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 21 | Leukocytosis |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 22 | Recurrent abscess formation |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 23 | Enteropathy |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 24 | Urinary tract infection |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 25 | Crohn's disease |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 26 | Cachexia |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 27 | (unusual) Viral infection |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 28 | Pleural empyema |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 29 | Pyelonephritis |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 30 | Neutrophilia |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 31 | Lung abscess |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 32 | HIV Infection |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 33 | Elevated C-reactive protein |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 34 | Respiratory distress |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 35 | Acne inversa |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 36 | Necrotizing fasciitis |
1 (5.9%) | 0 (0.0%) | 16 (94.1%) |
| 37 | Antinuclear antibodies |
0 (0.0%) | 1 (5.9%) | 16 (94.1%) |
| 38 | Autoimmunity |
0 (0.0%) | 1 (5.9%) | 16 (94.1%) |
| 39 | Autoimmune antibody positivity |
0 (0.0%) | 1 (5.9%) | 16 (94.1%) |
| 40 | anti-ENA antibodies |
0 (0.0%) | 1 (5.9%) | 16 (94.1%) |
Summary of treatment outcomes
[Considering only Definitive and Possible cases]
| Treatment ⓘ | Responses & clinical indications |
|---|---|
| Immunosuppressive agents | Absent (1) for unspecified |
| Infliximab | Good (1) for Elevated C-reactive protein & Fever & Neutrophilia |
| Corticosteroids | Absent (1) for unspecified |
| Anakinra | Absent (1) for unspecified |
| Interleukin Receptor Antagonist | Absent (1) for unspecified |
| Biological agents | Good (1) for Elevated C-reactive protein & Fever & Neutrophilia |
| Monoclonal antibodies | Good (1) for Elevated C-reactive protein & Fever & Neutrophilia |
| Intravenous immunoglobulin therapy | Unspecified (1) for unspecified |
| Antibiotics | Good (1) for Pyelonephritis & Urinary tract infection |
| Debridement | Good (1) for Cellulitis |
| Hysterectomy | Unspecified (1) for Chorioamnionitis |