RHOG

Inheritance Pattern: AR

Disease ID:MONDO:0800147

Submitter: ClinGen

RHOG deficiency was reported in relation to autosomal recessive hemaphagocytic lmphohistiocytosis in 2021 (Kalinichenko et al. PMID: 33513601). This is the only report associated with huma RhoG deficiency. The only proband presented marked cytopenias with low leukocytes and thrombocytes, low hemoglobin, hypertriglyceridemia, raised ferritin, and plasma soluble interleukin-2 receptor. The patient met the eight clinical criteria for HLH with a very early onset of didease (4 months of age). The patient is heterozygous compound for RhoG deficiency. The paternal allele carried a deletion that contains the entire RHOG gene (chr11:3848730-3881730); the maternal allele carries a missense mutation: c.511G>A; p.Glu171Lys. The patient cells showed null expression of RhoG and overexpression of the missense variant confirmed that the expression is severely reduced compared to WT RhoG protein. Experimental evidence includes RhoG expression in relevant tissues such as lymphocytes (Natural Killer cells, T and B lymphocytes), fibroblast. PMID: 35280994. Defective lytic activity and degranulation in NK cells and CD8+ T cells from patient cells. RHOG KO NK-92 Cell lines edited by CRISPcas9 showed that when cells do not express RHOG there is decreased lytic activity and degranulation as seen in patients’ cells. Moreover, RHOG KO mice model showed elevated immunoglobulin levels similar to the human RHOG deficiency. Neither KO mice or Patient T lymphocytes showed affected activation. In summary, RHOG deficiency is moderate associated with autosomal recessive familial hemophagocytic lymphohistiocytosis.

Inheritance Pattern: AR

Disease ID:MONDO:0015541

Submitter: PanelApp Australia