Information on EOPCV
Name: Early-onset pulmonary and cutaneous vasculitis | Acronym: EOPCV
Alt. names: HCK GOF | HCK-GOF
Gene: HCK | MOI: Autosomal dominant | Mechanism of action: Gain of Function
No. of cases in DB: 2 | First reported in: 2022
Last updated on: 2023-12-02 by Parsa Alizadeh
OMIM:
Orphanet: -
MONDO: -
DOID: -
ClinGen:
Description
Only one patient reported to date with a de novo activating mutation: p.Tyr515?. Patient presented with cutaneous vasculitis, inflammatory leukocyte infiltration of the lungs (pulmonary fibrosis) and skin, anemia and hepatosplenomegaly. It is biologically characterized by increased kinase activity of HCK mutant in vitro, and increased production of inflammatory cytokines (IL-1 , IL-6, IL-8, TNF- ) and ROS (PMID:34536415).
Management
Description of management option has not been reviewed yet.
Please mind that full curation of this condition has not been completed yet. It is currently ongoing.
Summary of clinical findings
[Considering only Definitive and Possible cases]
| Rank | Clinical phenotype | Present | Absent | Unreported |
|---|---|---|---|---|
| 1 | Abnormal spleen morphology |
1 (99.9%) | 0 (0.0%) | 0 (0.0%) |
| 2 | Hemosiderin-laden macrophages in bronchoalveolar fluid |
1 (99.9%) | 0 (0.0%) | 0 (0.0%) |
| 3 | Abnormal alveolar macrophage morphology |
1 (99.9%) | 0 (0.0%) | 0 (0.0%) |
| 4 | Pulmonary hemorrhage |
1 (99.9%) | 0 (0.0%) | 0 (0.0%) |
| 5 | Abnormal liver morphology |
1 (99.9%) | 0 (0.0%) | 0 (0.0%) |
| 6 | Petechiae |
1 (99.9%) | 0 (0.0%) | 0 (0.0%) |
| 7 | Vasculitis by anatomical site |
1 (99.9%) | 0 (0.0%) | 0 (0.0%) |
| 8 | Hepatosplenomegaly |
1 (99.9%) | 0 (0.0%) | 0 (0.0%) |
| 9 | Small vessel vasculitis |
1 (99.9%) | 0 (0.0%) | 0 (0.0%) |
| 10 | Vasculitis |
1 (99.9%) | 0 (0.0%) | 0 (0.0%) |
| 11 | Abnormal lymphoproliferation |
1 (99.9%) | 0 (0.0%) | 0 (0.0%) |
| 12 | Visceromegaly |
1 (99.9%) | 0 (0.0%) | 0 (0.0%) |
| 13 | Anemia |
1 (99.9%) | 0 (0.0%) | 0 (0.0%) |
| 14 | Diffuse alveolar hemorrhage |
1 (99.9%) | 0 (0.0%) | 0 (0.0%) |
| 15 | Purpura |
1 (99.9%) | 0 (0.0%) | 0 (0.0%) |
| 16 | Subcutaneous hemorrhage |
1 (99.9%) | 0 (0.0%) | 0 (0.0%) |
| 17 | Macular purpura |
1 (99.9%) | 0 (0.0%) | 0 (0.0%) |
| 18 | Abnormality of erythrocytes |
1 (99.9%) | 0 (0.0%) | 0 (0.0%) |
Age of onset
distribution
Please mind that full curation of this condition has not been completed yet. It is currently ongoing.
Summary of treatment outcomes
[Considering only Definitive and Possible cases]
| Treatment ⓘ | Responses & clinical indications |
|---|---|
| JAK inhibitor | Mild (1) for Petechiae & Purpura. Good (1) for Diffuse alveolar hemorrhage & Hepatosplenomegaly |
| Ruxolitinib [JAK inhibitor] |
Mild (1) for Petechiae & Purpura. Good (1) for Diffuse alveolar hemorrhage & Hepatosplenomegaly |
Please mind that full curation of this condition has not been completed yet. It is currently ongoing.
2 reported cases added to GenIA
| SubjectID | Sex | Fam.ID | AD | AFM | Validity | Country | Population | Reference & Pub.code |
|---|---|---|---|---|---|---|---|---|
| 105340 |
F | 215702 | 13 | 0 | Finland | Finnish | PMID:34536415 [1] | |
| 105343 |
F | 215705 | 13 | 0 | Finland | Finnish | PMID:34536415 [P1(I.1)] |
AD: Age at genetic diagnosis; AFM: age at first manifestation; PMID: PubMed ID; GRID: GenIA reference ID (ref. not in PubMed).