Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: HMOX1
Comment on list classification: As listed in the review of Hannah Knight, there are more than three unrelated cases with biallelic HMOX1 variants reported with asplenia. In addition, recurrent infections, recurrent fever, generalized erythematous rash, hemolysis, inflammation, nephritis, and joint pain were reported in these cases. Hence, this gene can be promoted to green rating in the next GMS review.Created: 13 Oct 2023, 5:21 p.m. | Last Modified: 13 Oct 2023, 5:21 p.m.
Panel Version: 4.45
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Heme oxygenase-1 deficiency, OMIM:614034
Multiple reports of asplenia in this condition:
PMID: 33066778 - boy born to nonconsanguineous parents who presented with early onset asplenia, recurrent infections, and associated flares with bone marrow histiocyte activation with worsening interstitial lung disease and joint pain. p.L89Sfs*24 and p.Ala88Profs*51
PMID: 9884342 - case mentioned previously - presented with recurrent fever, generalized erythematous rash, and joint pain, found to have no spleen. Complete deletion of exon2 was found in the maternal allele, and a 2 nucleotide deletion was present within exon3 of the paternal allele.
PMID: 21088618 - mentioned previously - girl with congenital asplenia, who presented with severe hemolysis, inflammation, nephritis. Homozygous for p.R44X
PMID: 22023467 - boy with hemolysis, inflammation, nephritis, and asplenia. Homozygous for p.R44X
PMID: 26526137 - affected boy with small spleen. Homozygous for p.R44XCreated: 9 Oct 2023, 10:56 a.m. | Last Modified: 9 Oct 2023, 10:56 a.m.
Panel Version: 4.35
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Heme oxygenase-1 deficiency
Publications
Comment on publications: Added publications suggested from external expert reviewCreated: 6 Jul 2018, 12:42 p.m.
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): HMOX .PanelApp HGNC gene symbol check: HMOX1 . IUIS Disease: Isolated congenital asplenia (ICA) due to HMOX deficiency . IUIS Inheritance: AR .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: Macrophages. IUIS Associated features: Hemolysis, nephritis, inflammation. IUIS Major category: Defects in Intrinsic and Innate Immunity. IUIS Subcategory: Other Inborn Errors of Immunity Related to Non-Hematopoietic TissuesCreated: 6 Jul 2018, 12:20 p.m.
Only one report of asplenia as part of this syndrome (phenotype dominated by haemolysis, endothelial inflammation)Created: 29 Jun 2018, 8:54 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
haemolysis; nephritis; asplenia; amyloidosis
Publications
Tag Q4_23_NHS_review tag was added to gene: HMOX1.
Gene: hmox1 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: HMOX1 were changed from Hemolysis, nephritis, inflammation; Defects in Intrinsic and Innate Immunity; amyloidosis to Heme oxygenase-1 deficiency, OMIM:614034; Hemolysis, nephritis, inflammation; Defects in Intrinsic and Innate Immunity; amyloidosis
Publications for gene: HMOX1 were set to 9884342; 21088618; 22023467; 26526137; 3306677
Publications for gene: HMOX1 were set to 9884342; 21088618
Tag Q4_23_promote_green tag was added to gene: HMOX1.
2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.
Gene: hmox1 has been classified as Red List (Low Evidence).
Mode of inheritance for gene: HMOX1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HMOX1 were set to Hemolysis, nephritis, inflammation; Defects in Intrinsic and Innate Immunity; amyloidosis
Publications for gene: HMOX1 were set to 9884342; 21088618
Phenotypes for gene HMOX1 were set to Hemolysis, nephritis, inflammation, Defects in Intrinsic and Innate Immunity
HMOX1 was added to Primary immunodeficiency disorders panel. Sources: IUIS Classification February 2018
HMOX1 was created by Louise Daugherty