Information on CVID15
Basic details
Name: Immunodeficiency, common variable, 15 | Acronym: CVID15
Alt. names: Sec61a1 deficiency | PCD1 | translocon deficiency
Gene: SEC61A1 | MOI: Autosomal dominant | Mechanism of action: Haploinsufficiency
No. of cases in DB: 13 | First reported in: 2018
Last updated on: 2024-01-14 09:37:52 by Xiao P. Peng
Description
Schubert et al. (2018) identified thirteen patients from 2 unrelated families presenting with a predominantly antibody deficiency phenotype without neutropenia or kidney disease (PMID: 28782633). These patients have early-onset, severe, recurrent bacterial infections primarily involving the sinorespiratory and GI tracts and show deficits in all class-switched isotypes (IgM, IgG, IgA) as well as suboptimal vaccine responses. Total B and T cell counts as well as their subpopulations are largely normal, with only reductions in a small population of peripheral CD27+CD38high plasmablasts, leading to the identification of a cell-intrinsic defect in plasma cell differentiation.
Management
Patients appear to show significant clinical improvement in terms of infections after initiation of Ig replacement therapy.
13 reported cases added to GenIA
| SubjectID | Sex | Fam.ID | AD | AFM | Validity | Country | Population | Reference & Pub.code |
|---|---|---|---|---|---|---|---|---|
101727 |
M | 210300 |
54 | U.S.A. | North American | PMID:28782633 [Fam.I:II.1(P1)] | ||
| 101731 |
M | 210300 |
U.S.A. | North American | PMID:28782633 [Fam.I:III.3(P2)] | |||
| 101732 |
M | 210300 |
26 | 0 | U.S.A. | North American | PMID:28782633 [Fam.I:III.4(P3)] | |
| 101733 |
M | 210300 |
24 | U.S.A. | North American | PMID:28782633 [Fam.I:III.6(P4)] | ||
| 101735 |
F | 210300 |
21 | U.S.A. | North American | PMID:28782633 [Fam.I:III.8(P5)] | ||
| 101736 |
M | 210300 |
20 | 1 | U.S.A. | North American | PMID:28782633 [Fam.I:III.9(P6)] | |
| 101737 |
M | 210300 |
17 | 9 | U.S.A. | North American | PMID:28782633 [Fam.I:III.10(P7)] | |
| 101738 |
M | 210300 |
14 | 6 | U.S.A. | North American | PMID:28782633 [Fam.I:III.11(P8)] | |
| 101740 |
M | 210300 |
11 | 1 | U.S.A. | North American | PMID:28782633 [Fam.I:III.13(P9)] | |
| 101741 |
F | 210300 |
8 | 1 | U.S.A. | North American | PMID:28782633 [Fam.I:III.14(P10)] | |
| 101780 |
M | 210923 |
8 | 0 | Germany | German | PMID:28782633 [Fam.II:III.1(P3)] | |
| 101782 |
F | 210923 |
Germany | German | PMID:28782633 [Fam.II:II.2(P2)] | |||
| 101783 |
F | 210923 |
65 | Germany | German | PMID:28782633 [Fam.II:I.2(P1)] |
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 | Hypogammaglobulinemia |
11 (84.6%) | 1 (7.7%) | 1 (7.7%) |
| 2 | Decreased IgA levels |
10 (76.9%) | 2 (15.4%) | 1 (7.7%) |
| 3 | Decreased IgG levels |
10 (76.9%) | 2 (15.4%) | 1 (7.7%) |
| 4 | Decreased IgM levels |
10 (76.9%) | 2 (15.4%) | 1 (7.7%) |
| 5 | Absent ab-response to pneumococcal polysaccharide vaccine |
9 (69.2%) | 0 (0.0%) | 4 (30.8%) |
| 6 | (unusual) Respiratory tract infection |
8 (61.5%) | 0 (0.0%) | 5 (38.5%) |
| 7 | Otitis media |
4 (30.8%) | 0 (0.0%) | 9 (69.2%) |
| 8 | Reduced ab-response to tetanus vaccine |
4 (30.8%) | 3 (23.1%) | 6 (46.2%) |
| 9 | Recurrent upper respiratory tract infection |
4 (30.8%) | 0 (0.0%) | 9 (69.2%) |
| 10 | Lung disease |
4 (30.8%) | 0 (0.0%) | 9 (69.2%) |
| 11 | Pneumonia |
4 (30.8%) | 0 (0.0%) | 9 (69.2%) |
| 12 | (unusual) Viral infection |
3 (23.1%) | 0 (0.0%) | 10 (76.9%) |
| 13 | Recurrent lower respiratory tract infections |
2 (15.4%) | 0 (0.0%) | 11 (84.6%) |
| 14 | Subglottic laryngitis |
2 (15.4%) | 0 (0.0%) | 11 (84.6%) |
| 15 | Septicaemia |
2 (15.4%) | 0 (0.0%) | 11 (84.6%) |
| 16 | Raynaud phenomenon |
2 (15.4%) | 0 (0.0%) | 11 (84.6%) |
| 17 | Atopy |
2 (15.4%) | 0 (0.0%) | 11 (84.6%) |
| 18 | Hearing impairment |
2 (15.4%) | 0 (0.0%) | 11 (84.6%) |
| 19 | Abscess |
1 (7.7%) | 0 (0.0%) | 12 (92.3%) |
| 20 | Chronic otitis media |
1 (7.7%) | 0 (0.0%) | 12 (92.3%) |
| 21 | Cow milk allergy |
1 (7.7%) | 0 (0.0%) | 12 (92.3%) |
| 22 | Absent specific antibody response to tetanus vaccine |
1 (7.7%) | 0 (0.0%) | 12 (92.3%) |
| 23 | Decreased specific anti-polysaccharide antibody level |
1 (7.7%) | 0 (0.0%) | 12 (92.3%) |
| 24 | (unusual) Giardiasis |
1 (7.7%) | 0 (0.0%) | 12 (92.3%) |
| 25 | Allergy |
1 (7.7%) | 0 (0.0%) | 12 (92.3%) |
| 26 | Transient hypogammaglobulinemia of infancy |
1 (7.7%) | 0 (0.0%) | 12 (92.3%) |
| 27 | Food allergy |
1 (7.7%) | 0 (0.0%) | 12 (92.3%) |
| 28 | Varicella zoster virus infection |
1 (7.7%) | 0 (0.0%) | 12 (92.3%) |
| 29 | Tonsillitis |
1 (7.7%) | 0 (0.0%) | 12 (92.3%) |
| 30 | Bronchitis |
1 (7.7%) | 0 (0.0%) | 12 (92.3%) |
| 31 | Orbital cellulitis |
1 (7.7%) | 0 (0.0%) | 12 (92.3%) |
| 32 | Asthma |
1 (7.7%) | 0 (0.0%) | 12 (92.3%) |
| 33 | negative ab-response to diphtheria vaccine |
0 (0.0%) | 1 (7.7%) | 12 (92.3%) |
| 34 | Abnormal B cell count |
0 (0.0%) | 1 (7.7%) | 12 (92.3%) |
Summary of treatment outcomes
[Considering only Definitive and Possible cases]
| Treatment ⓘ | Responses & clinical indications |
|---|