Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: GIMAP5

I don't know

PMID:29382851 - A patient with GIMAP5 homozygous loss-of-function variant (p.Leu204Pro) was reported with splenomegaly and lymphopenia. In addition, this phenotype was also recapitulated in mouse model.

PMID:33956074 - 8 individuals from 4 unrelated families were reported with portal hypertension. One of five individuals from family 2 (died at 17 years of age) had recurrent infections. Although p.Leu223Phe variant was identified in all other members of this family, sequencing was not done for this individual with recurrent infections as he was already deceased.

Created: 2 Nov 2023, 12:07 p.m. | Last Modified: 2 Nov 2023, 12:07 p.m.

Panel Version: 4.108

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 29382851
• 33956074

I don't know

Paper now available. At least one patient first presented with immune phenotype (recurrent infection)

Created: 18 Oct 2023, 11:41 a.m. | Last Modified: 18 Oct 2023, 11:41 a.m.

Panel Version: 4.50

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Portal hypertension, noncirrhotic, 2, MIM# 619463

Publications

• 33956074

Green List (high evidence)

Now published:
8 individuals from 4 unrelated families reported with onset of disease in the first decade of life. Clinical features included jaundice, hyperbilirubinaemia, pancytopaenia, including neutropaenia, lymphopaenia, and thrombocytopaenia, hepatosplenomegaly, and oesophageal varices. Some individuals had recurrent infections or features suggestive of an immunodeficiency. Liver biopsy was notable for the absence of cirrhosis and the presence of nodular regeneration.

Created: 7 Aug 2021, 7:41 a.m. | Last Modified: 7 Aug 2021, 7:41 a.m.

Panel Version: 2.452

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Portal hypertension, noncirrhotic, 2, MIM# 619463

Publications

• 33956074

Cannot access new publication identified by Zornitza Stark (PMID:33956074) - free text will be available from 05/01/2022. OMIM entry states that "some patients may have recurrent infections or features suggestive of an immunodeficiency" but it is unclear how many individuals were affected and to what extent. Liver dysfunction (portal hypertension, liver failure) seems to be the more prominent phenotype in these cases but currently there are no relevant PanelApp panels for this. Therefore, I will maintain the Amber rating at this time, until publications become available or further evidence emerges.

Created: 12 Aug 2021, 11:18 a.m. | Last Modified: 12 Aug 2021, 11:18 a.m.

Panel Version: 2.455

Comment on list classification: New gene added by Boaz Palterer. 4 unrelated families with an immunodeficiency disorder and difference biallelic LoF variants in the GIMAP5 gene. Clinical improvement in Gimap5-deficient mice and a human patient was observed following treatment with rapamycin (mTORC1 inhibitor)

Although there are sufficient cases with a relevant phenotype, rating this gene Amber while pending publication of the Park 2021 article, as information can change from the initial bioRxiv upload to peer-reviewed publication. Added 'watchlist' tag and will re-curate when the paper is published.

Created: 1 Apr 2021, 10:40 a.m. | Last Modified: 1 Apr 2021, 10:40 a.m.

Panel Version: 2.405

Red List (low evidence)

Park et al. (https://www.biorxiv.org/content/10.1101/2021.02.22.432146v1.full.pdf) identified biallelic mutations in GIMAP5 in 10 subjects from 4 kindreds with severe progressive
lymphopenia, autoimmunity, immunodeficiency, and liver disease
Sources: Literature

Created: 24 Feb 2021, 9:42 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
lymphopenia; autoimmunity; immunodeficiency; liver disease