ITPKB

Inheritance Pattern: AR

Disease ID:MONDO:0800140

Submitter: ClinGen

ITPKB was first reported in relation to autosomal recessive ITPKB deficiency in 2020 (Almutairi A, et al., PMID: 31987846). One frameshift variant has been reported in one proband in one publication (PMIDs: 31987846). The proband was born to consanguineous parents and presented with failure to thrive, oral thrush, recurrent pneumonia, skin abscesses, anemia, leukopenia, neutropenia, thrombocytopenia, and profound CD3+ CD4+ and CD8+ cell lymphopenia, consistent with T-B+NK+ severe combined immunodeficiency. The parents and unaffected sibling were heterozygous for the same variant and none had a history of recurrent infections. CD3+, CD4+, CD8+, and CD19+ B-cell numbers were normal in the parents. To date, the only reported variant is a frameshift at the 3’ end of the gene that may escape nonsense mediated decay. In vitro functional studies showed that this variant caused reduced expression and absent kinase activity. The mechanism of pathogenicity appears to be loss of function. This gene-disease relationship is also supported by animal models, rescue studies, and functional assays (PMIDs: 31987846, 22981169, 14517551). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen SCID-CID GCEP on the meeting date [November 16, 2023] (SOP Version 9)].

Inheritance Pattern: AR

Disease ID:MONDO:0015974

Submitter: PanelApp Australia

Inheritance Pattern: Unknown

Disease ID:MONDO:0007661

Submitter: Labcorp Genetics (formerly Invitae)