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Primary immunodeficiency or monogenic inflammatory bowel disease v9.58 HCK Arina Puzriakova Publications for gene: HCK were set to 34536415
Primary immunodeficiency or monogenic inflammatory bowel disease v9.27 HCK Ida Ertmanska Phenotypes for gene: HCK were changed from Autoinflammatory disease; Cutaneous vasculitis; Lung inflammation; Lung fibrosis; Interstitial lung disease to Autoinflammation with pulmonary and cutaneous vasculitis, OMIM:620296 autoinflammation with pulmonary and cutaneous vasculitis, MONDO:0957204
Primary immunodeficiency or monogenic inflammatory bowel disease v9.26 HCK Ida Ertmanska Mode of inheritance for gene: HCK was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v9.25 HCK Ida Ertmanska changed review comment from: Comment on list classification: There are now 5 unrelated families reported in literature with heterozygous HCK variants and autoinflammatory features, most commonly cutaneous and/or pulmonary vasculitis. Recurrent infections were noted in 2 unrelated individuals. Hence, the Autoinflammatory disorders panel may be more appropriate for this gene - leaving as Amber on Primary immunodeficiency or monogenic inflammatory bowel disease.; to: Comment on list classification: There are now 5 unrelated families reported in literature with heterozygous HCK variants and autoinflammatory features, most commonly cutaneous and/or pulmonary vasculitis. Recurrent infections were noted in 2 unrelated individuals (PMIDs: 34536415, 41382121) . Hence, the Autoinflammatory disorders panel may be more appropriate for this gene - leaving as Amber on Primary immunodeficiency or monogenic inflammatory bowel disease.
Primary immunodeficiency or monogenic inflammatory bowel disease v9.25 HCK Ida Ertmanska changed review comment from: Comment on list classification: There are now 4 unrelated families reported in literature with heterozygous HCK variants and autoinflammatory features, most commonly cutaneous and/or pulmonary vasculitis. Recurrent infections were noted in 2 unrelated individuals. Hence, the Autoinflammatory disorders panel may be more appropriate for this gene - leaving as Amber on Primary immunodeficiency or monogenic inflammatory bowel disease.; to: Comment on list classification: There are now 5 unrelated families reported in literature with heterozygous HCK variants and autoinflammatory features, most commonly cutaneous and/or pulmonary vasculitis. Recurrent infections were noted in 2 unrelated individuals. Hence, the Autoinflammatory disorders panel may be more appropriate for this gene - leaving as Amber on Primary immunodeficiency or monogenic inflammatory bowel disease.
Primary immunodeficiency or monogenic inflammatory bowel disease v9.25 HCK Ida Ertmanska Classified gene: HCK as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v9.25 HCK Ida Ertmanska Added comment: Comment on list classification: There are now 4 unrelated families reported in literature with heterozygous HCK variants and autoinflammatory features, most commonly cutaneous and/or pulmonary vasculitis. Recurrent infections were noted in 2 unrelated individuals. Hence, the Autoinflammatory disorders panel may be more appropriate for this gene - leaving as Amber on Primary immunodeficiency or monogenic inflammatory bowel disease.
Primary immunodeficiency or monogenic inflammatory bowel disease v9.25 HCK Ida Ertmanska Gene: hck has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v9.24 HCK Ida Ertmanska changed review comment from: PMID: 41382121 Berdeli, Ismayilova, & Gürbüz 2025
Report of a 6-year-old female patient with recurrent fevers, cutaneous petechial rashes, chronic cough, exertional dyspnea, and suspected recurrent lower respiratory tract infections since age 1.5 years. No cutaneous manifestations were observed, but elevated acute-phase reactants and pulmonary findings were noted. WES revealed a heterozygous splice variant c.1016-5T>C in HCK.

PMID: 41920357 Price-Kuehne et al., 2026
Family A - female proband with systemic vasculitis due to a de novo heterozygous variant in HCK c.1545 C > A, p.(Tyr515Ter) - exome seq; she was treated with allogeneic haematopoietic stem cell transplantation. She subsequently developed epistaxis, haemolacria and blood-stained stools leading to iron-deficiency anaemia requiring transfusion. From 18 months of age, she developed chronic cough and haemoptysis; chest CT scan demonstrated enlarged hilar lymph nodes and bilateral inflammatory changes and pulmonary haemorrhage.

Family B - male proband with a cutaneous-limited phenotype (purpuric rash, predominantly affecting the limbs, starting at 4hrs after birth); Skin biopsy showed leukocytoclastic vasculitis; WES identified a novel HCK missense variant c.1565A > T, (p.Tyr522Phe). Proband's father is het for the same HCK variant, and also had neonatal-onset leukocytoclastic vasculitis, now healthy.; to: PMID: 41920357 Price-Kuehne et al., 2026
Family A - female proband with systemic vasculitis due to a de novo heterozygous variant in HCK c.1545 C > A, p.(Tyr515Ter) - exome seq; she was treated with allogeneic haematopoietic stem cell transplantation. She subsequently developed epistaxis, haemolacria and blood-stained stools leading to iron-deficiency anaemia requiring transfusion. From 18 months of age, she developed chronic cough and haemoptysis; chest CT scan demonstrated enlarged hilar lymph nodes and bilateral inflammatory changes and pulmonary haemorrhage.

Family B - male proband with a cutaneous-limited phenotype (purpuric rash, predominantly affecting the limbs, starting at 4hrs after birth); Skin biopsy showed leukocytoclastic vasculitis; WES identified a novel HCK missense variant c.1565A > T, (p.Tyr522Phe). Proband's father is het for the same HCK variant, and also had neonatal-onset leukocytoclastic vasculitis, now healthy.

PMID: 41382121 Berdeli, Ismayilova, & Gürbüz 2025
Report of a 6-year-old female patient with recurrent fevers, cutaneous petechial rashes, chronic cough, exertional dyspnea, and suspected recurrent lower respiratory tract infections since age 1.5 years. No cutaneous manifestations were observed, but elevated acute-phase reactants and pulmonary findings were noted. WES revealed a heterozygous splice variant c.1016-5T>C in HCK.

doi: 10.11648/j.ajp.20190504.15 Bronz et al., 2019
Family with suspected Finkelstein-Seidlmayer disease (benign small-vessel leukocytoclastic vasculitis) - affected mother and her 3 sons. History of red-to-purpuric skin lesions with neonatal onset, no systemic involvement. WES detected a heterozygous HCK variant c.1555G>T; p.Glu519* in all 4 affected individuals. Variant not present in gnomAD v4.1.1.
Primary immunodeficiency or monogenic inflammatory bowel disease v9.24 HCK Ida Ertmanska reviewed gene: HCK: Rating: AMBER; Mode of pathogenicity: None; Publications: 41382121, 41920357; Phenotypes: Autoinflammation with pulmonary and cutaneous vasculitis, OMIM:620296, autoinflammation with pulmonary and cutaneous vasculitis, MONDO:0957204; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v8.99 HCK Boaz Palterer edited their review of gene: HCK: Added comment: Two additional reports:
Priece-Kuehne et al. describing 3 additional kindreds with HCK GOF, similar phenotype and mechanism ( https://link.springer.com/article/10.1007/s10875-026-01998-z )
Berdeli et al. additional kindred with similar phenotype and mechanism (https://pmc.ncbi.nlm.nih.gov/articles/PMC12801773/)

Now reaching criteria for green rating; Changed rating: GREEN; Changed publications to: 34536415, 41382121; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary immunodeficiency or monogenic inflammatory bowel disease v2.568 HCK Arina Puzriakova Mode of inheritance for gene: HCK was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Primary immunodeficiency or monogenic inflammatory bowel disease v2.567 HCK Arina Puzriakova Classified gene: HCK as Red List (low evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v2.567 HCK Arina Puzriakova Added comment: Comment on list classification: Single case reported to date as per review by Boaz Palterer. Rating Red until further cases emerge.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.567 HCK Arina Puzriakova Gene: hck has been classified as Red List (Low Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v2.550 HCK Boaz Palterer gene: HCK was added
gene: HCK was added to Primary immunodeficiency. Sources: Literature
Mode of inheritance for gene: HCK was set to Unknown
Publications for gene: HCK were set to 34536415
Phenotypes for gene: HCK were set to Autoinflammatory disease; Cutaneous vasculitis; Lung inflammation; Lung fibrosis; Interstitial lung disease
Penetrance for gene: HCK were set to unknown
Mode of pathogenicity for gene: HCK was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: HCK was set to RED
Added comment: Kanderova et al. described a single patient with an autoinflammatory phenotype characterized by early-onset cutaneous vasculitis and lung inflammation leading to fibrosis.
A de novo truncating mutation (p.Tyr515*) in the HCK leading to the loss of the C-terminal inhibitory tyrosine Tyr522 was identified.
Variant pathogenicity was confirmed ex vivo in primary cells and in vitro in transduced cell lines.
Sources: Literature