Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: HMOX1

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 3 May 2024, 8:36 p.m. | Last Modified: 3 May 2024, 8:36 p.m.

Panel Version: 5.3

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

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

I don't know

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.R44X

Created: 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

• 3306677
• 9884342
• 21088618
• 22023467
• 26526137

Comment on publications: Added publications suggested from external expert review

Created: 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 Tissues

Created: 6 Jul 2018, 12:20 p.m.

Red List (low evidence)

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

• 9884342
• 21088618